Podcasts about acmg

Increasing Situational Awareness with Jerome DavidHow can we improve our situational awareness so that we don't miss important information? Situational awareness is the ability to perceive, understand, and effectively respond to one's situation. This includes being able to recognize the hazards around us, the state of ourselves and the people we are with, changing conditions, and the overall direction that the situation we are in is likely to go.When it comes to delivering adventure, a lack of situational awareness can impact our judgment in ways that can either boost or degrade our decision making and our ability to react to the situations that we are in.In this episode of Delivering Adventure, ACMG Ski Guide Jerome David joins us to explore how we can boost our situational awareness. Jerome shares some examples from his career as a Heli ski guide and bike park patroller as well as some practical strategies we can all use.Jerome currently works at Whistler Heli skiing as the lead guide and guide manager. He has also worked as a ski and bike patroller and trail builder.Key TakeawaysTo improve our situational awareness we can:Take Time to Refocus (When Needed): Living in the moment by concentrating on the task at hand can reduce distraction and complacency. It can also help us to switch from system 2 thinking where slower reasoned thinking can consume our bandwidth at the expense of being able to process information and react faster with our system 1 thinking.Boosting Bandwidth: People are like computers, they only have so much processing power at anyone time. To boost our ability to process everything around us, we may need to slow things down.Be aware of Transitions: When we switch activities or change the intensity of tasks, we need to make sure that we refocus. Failing to do so can cause our minds to become focused on what we were just doing, instead of paying attention to what we are doing in that moment.An example of a transitions to be aware of include going from low risk to high-risk situations or vice versa.Reduce External Distractions: This can include storing phones, giving people less instruction in complex situations or waiting for other people to pass you on a trail or climb so that you can stay focused.Plan Ahead: This can include making lists so that you don't miss anything. Briefing people on what to expect, what they should look for or be aware of can also help to switch people on.Guest BioJerome David has been working on Snow and Dirt in Whistler since 1998. On the road to becoming an ACMG ski guide, he worked 11 years with Whistler Blackcomb Patrol. He has been ski guiding for the past 7 years. In the summers, Jerome has previously had a long career working as Whistler Mountain Bike Park patrol. The last years he has been building and maintaining Mountain Bike trails. Currently, he works for AlpX and oversees the summer program there. In the Winter Jerome is lead guide and guide manager at Whistler Heli-Skiing.Guest LinksThinking Fast and Slow: https://en.wikipedia.org/wiki/Thinking,_Fast_and_SlowWhistler Heli Skiing: https://www.whistlerblackcomb.com/explore-the-resort/activities-and-events/whistler-heli-skiing/whistler-heli-skiing.aspxFollow or SubscribeDon't forget to follow the show!Share & Social Linkshttps://linktr.ee/deliveringadventurehttps://deliveringadventure.com/

Episode 8.29 Unique Summer Careers The Northern Hemisphere winter is over and avy pros are returning to summer jobs. For many, this is forest firefighting – a natural fit with opposing seasons and complementary skill sets. For some, however, the summer provides an opportunity to completely unplug from the challenges of winter work and pursue other passions. In this episode, host Dom Baker speaks with two ski guides who have each built businesses pursuing a summer passion. Kevin Armstong, an ACMG ski guide, builds hand-welded custom bikes for passionate riders. Whether for road, gravel, or singletrack, Six Mile Bikes builds unique, made to order, dream bikes! Eric Chevalier is a veteran ski guide and the guiding manager at Selkirk Cat Skiing. He is also a long-time shipwright – building and restoring wooden boats. The Copper Nail Wooden Boat Shop offers world-class wooden boat restoration and building services. Tune in to hear the highs, lows and unexpected parallels between ski guiding and chasing a passion in a quiet workshop. Music for this episode by Gravy @gravy.tunes www.wyssenavalanche.com www.gordini.com www.opensnow.com www.sixmilebikes.com www.woodenboatshop.ca

How can we ever know when we should turn back or keep going? On paper, the safest decision to make is often to turn around or choose the route that takes on less risk. However, in reality, delivering adventure isn't always about picking the safest choice. At the core of every adventure is an element of risk taking. Being able to decide when to go for it, and when not to, is a defining trait of professional adventure guides and instructors.Helping us to identify when it's okay to keep going is Mike Adolph. Mike is an ACMG / IFMGA Mountain Guide and the current technical director of the Association of Canadian Mountain Guides. There are a number of factors that can hold us back from continuing onwards towards an objective including self doubt, fear, and uncertainty.We discuss some key strategies with Mike that we can use that can help us to determine if we should abort a plan or whether we are well positioned to keep going.Key Takeaways:How can we know when we should push forward and keep going with a plan when we may feel like doing the opposite? A few of the strategies that can help to guide our decision making include:Set goals around experiences: Instead of hard destinations or milestones, make it about the experience. When it comes to delivering adventure, we can box ourselves in by setting our expectations around achieving certain objectives.Identifying data points that support the decision to continue: This includes the amount of time taken to accomplish a task, competency level of skills, the interest level of group, the weather, the conditions, the amount of risk and the amount risk tolerance within the group.Remove pressure from the leader: Talk to the group for their feedback to ensure you are not the one driving the group or holding them back.If uncertainty is rising, ask yourself why: This uncertainty could include self doubt, the ability level of yourself or the group to handle the situation, the interest level of everyone involved, the conditions, and the actual route or path you want to take.Don't make a decision until you have to: This allows us the opportunity to collect as much information as possible before making a commitment. Guest BioMike Adolph is an ACMG / IFMGA Mountain Guide and the current technical director of the Association of Canadian Mountain Guides. In addition to guiding custom outdoor adventures for small groups, Mike also works as a guide trainer and examiner for the ACMG's Training and Assessment Program.Mike started in the outdoor industry in 1994 after his family, in a joint venture, opened the Sheiling Mountain Lodge and the Center for Outdoor Education in Nordegg, Alberta. He completed his final ACMG exam and received his IFMGA International Federation of Mountain Guides Association Mountain Guide designation in 2009. He always admired his instructors and examiners, even if they were a bit harsh at times, which lead to him getting involved with the instructor/examiner team in 2012. When the job posting for the interim ACMG technical director came up in 2018, he thought, why not? The mountains have taught him to be open to all possibilities, have several options and go with the flow. I feel lucky to have this as a career and am extremely grateful to my loving and understanding wife Jennifer and our two boys Lucas and Tyler.Guest LinksACMG Technical Manuals: https://www.acmg.ca/03public/resources/publications.aspxAssociation of Mountain Guides: www.acmg.caDavid Thomson Via Ferratas: www.viaferratacanada.comMike Adolph Email:

Have you ever pushed forward with something even when it became clear that you should probably change your plan or abort? If so, you may have succumbed to plan continuation bias. When this happens, we can become predisposed to continue towards completing our original plan, even when conditions change, or new information becomes known that indicates that continuing on is not advisable.Mike Adolph joins us to discuss some of the strategies that we can use to recognize and manage plan continuation bias. Mike Adolph is an ACMG / IFMGA Mountain Guide and is the current Technical Director of the Association of Canadian Mountain Guides.Mike dips into his extensive guiding and instructing experience to share some great examples and advice.Key TakeawaysWhat is plan continuation bias: It is when a person ignores the fact that conditions or the situation has changed in a way that should cause them to rethink their initial plan, but the person decides to push on towards their objective anyway.Reasons for plan continuation bias: There are often a number of human factors at play including pressure to keep going from others, a need or desire to make money if you are getting paid to keep going, and a belief that we are more likely to experience a positive outcome. We may also end up ignoring or downplaying information that indicates that we should change course.Set key decisions points beforehand: For example, we will decide if we continue once we reach the ridge, or after lunch, or once we have worked on this skill.Removing pressures beforehand: Examples of this can include communicating expectations, decision points and the overall plan beforehand.Guest BioMike Adolph is an ACMG / IFMGA Mountain Guide and the current technical director of the Association of Canadian Mountain Guides. In addition to guiding custom outdoor adventures for small groups, Mike also works as a guide trainer and examiner for the ACMG's Training and Assessment Program.Mike started in the outdoor industry in 1994 after his family, in a joint venture, opened the Sheiling Mountain Lodge and the Center for Outdoor Education in Nordegg, Alberta. He completed his final ACMG exam and received his IFMGA International Federation of Mountain Guides Association Mountain Guide designation in 2009. He always admired his instructors and examiners, even if they were a bit harsh at times, which lead to him getting involved with the instructor/examiner team in 2012. When the job posting for the interim ACMG technical director came up in 2018, he thought, why not? The mountains have taught him to be open to all possibilities, have several options and go with the flow. I feel lucky to have this as a career and am extremely grateful to my loving and understanding wife Jennifer and our two boys Lucas and Tyler.Guest LinksACMG Technical Manuals: https://www.acmg.ca/03public/resources/publications.aspxAssociation of Mountain Guides: www.acmg.caDavid Thomson Via Ferratas: www.viaferratacanada.comMike Adolph Email: msadolph@gmail.comMike Adolph Instagram: @ mikeatcoeAvalanche Hour with Mike Adolph: https://soundcloud.com/user-23585762/avalanche-hour-podcast-mike-adolph-acmg-10Follow or SubscribeDon't forget to follow the show!Share & Social Linkshttps://linktr.ee/deliveringadventure

Why is it so hard to make good decisions? One of the factors has to do with what are called the human factors. These include cognitive biases, heuristics, personal motivations, and preferences.One person who sees the human factors in high consequence environments is Mike Adolph. Mike is an ACMG / IFMGA Mountain Guide and the current Technical Director of the Association of Canadian Mountain Guides.In this episode, Mike helps us to understand what human factors are, what some of the more common ones are and what we can do to reduce their negative impact on our decision-making abilities.Guest BioMike Adolph is an ACMG / IFMGA Mountain Guide and the current technical director of the Association of Canadian Mountain Guides. In addition to guiding custom outdoor adventures for small groups, Mike also works as a guide trainer and examiner for the ACMG's Training and Assessment Program.Mike started in the outdoor industry in 1994 after his family, in a joint venture, opened the Sheiling Mountain Lodge and the Center for Outdoor Education in Nordegg, Alberta. He completed his final ACMG exam and received his IFMGA International Federation of Mountain Guides Association Mountain Guide designation in 2009. He always admired his instructors and examiners, even if they were a bit harsh at times, which lead to him getting involved with the instructor/examiner team in 2012. When the job posting for the interim ACMG technical director came up in 2018, he thought, why not? The mountains have taught him to be open to all possibilities, have several options and go with the flow. I feel lucky to have this as a career and am extremely grateful to my loving and understanding wife Jennifer and our two boys Lucas and Tyler.Guest LinksAssociation of Mountain Guides: www.acmg.caDavid Thomson Via Ferratas: www.viaferratacanada.comMike Adolph Email: msadolph@gmail.comMike Adolph Instagram: @ mikeatcoeAvalanche Hour with Mike Adolph: https://soundcloud.com/user-23585762/avalanche-hour-podcast-mike-adolph-acmg-10Follow or SubscribeDon't forget to follow the show!Share & Social Linkshttps://linktr.ee/deliveringadventure

Drew Nylen lives in northern British Columbia, on the Alaskan border, in a town of 300 people. His interest for Telemark skiing began in his youth when he started working at his local gear shop and was able to get his first freeheel setup. He's an ACMG apprentice ski guide who will be taking his full ski exam in April. His extensive guiding has taken him to the Arctic, including: Baffin Island, Greenland, and more. Currently he's working as an avalanche forecaster and field technician for Avalanche Canada. Find Drew Online: IG: https://www.instagram.com/drewnylen Guiding Services: https://yamnuska.com/ Join my YouTube channel to get access to perks: https://www.youtube.com/channel/UC9tPPZqLPCw2q4-tu9q3Ynw/join Here is our latest technique video for you to check out: https://youtu.be/WOu6G2-nKGs Check out our website and online store: https://www.freeheellife.com/ Our weekly e-mail newsletter is a great way to stay in contact with all of our content, events, product launches, etc. You can sign up here: https://bit.ly/FHLMailingList #telemark #spreadtelemark #freeheellife #skiing

Stas Beskin is known for soloing big bold climbs, such as Rainbow Serpent and Fearful Symmetry, two of the most iconic WI6s in the Canadian Rockies.It's one thing to solo big flows, it's another to do it on freestanding pillars about as wide as your shoulders. But he does that too. And he does so without swinging his tools.Stas' conception of ice climbing revolves around displacing as little ice as possible. It's an adaptive strategy that means different things in different situations, but it's always about fitting one's body and style to the ice in front of you – it's about being attuned to the environment and trying to fit it, not the other way around... Resources and links:Stas is a rock and ice climbing guide, specializing in multi-pitches. If you'd like to book a day out with Stas, you can connect with him at wildice.ca.For a bit more about Stas, Ian Welsted, an ACMG alpine guide, wrote a great profile in the October/November 2022 issue of Gripped.In this video, Stas shares techniques for scratching and climbing thin pillars. And here is an article (one of many) about hard mixed routes he is putting up.Find the rest of the notes, timestamps, resources, and more on the episode page. Credits:Original photo used in cover image by Caro Ouellet (@ouellet.caro).Intro music by Hannah Noelle Enomoto (thanks, sis!). Patreon:For the price of a beer per month, you can help us produce episodes like this and much, much more. If you've been enjoying the podcast this season, consider supporting us on Patreon. 

Part 2 of Caleb Merril and Dom Baker's conversation with Eirik Sharp – the President of the Canadian Avalanche Association (CAA). In part 2 Eirik shares his experiences from a diverse career in almost every corner of the avalanche world. From ski patrol to research, ski guiding to avalanche forecasting in remote places – Eirik has tales to tell and thoughtful reflections to learn from. Dig in to this gem of a conversation. Eirik is a long-time avalanche professional based in Whitehorse, Yukon. Originally from Norway, he grew up skiing backcountry and has worked in the snow for 18 years as a researcher, forecaster, educator, consultant, and ACMG ski guide. He has an M.Sc. in GIS with research focused on applications of machine learning to avalanche mapping. He currently works on the Alpine Solutions Avalanche Services engineering team, specializing in terrain modelling and avalanche risk assessment. However, he still gets out into the field to support industrial operational avalanche risk management programs as much as he can through the winter. Eirik is passionate about supporting, promoting, and elevating professional avalanche practice in Canada; he worked for ten years as an instructor with the Canadian Avalanche Association's industry training program and has served as President of the CAA since 2022. Music for this episode by Gravy @gravy.tunes Episode produced by Wes Gregg at Trigger Backcountry Adventures www.avalancheassociation.ca www.wyssenavalanche.com www.gordini.com www.beaconguidebooks.com

Caleb Merril and Dom Baker are joined by Eirik Sharp – the President of the Canadian Avalanche Association (CAA). CAA is the professional organization that ensures a high standard of practice for avalanche workers in Canada. The CAA Industry Training Program is registered private post-secondary training institution that provides the professional level avalanche training for avalanche practitioners in Canada. The CAA also provides the information sharing system for avalanche operations in Canada and beyond – InfoEX. In part one Eirik talks about the CAA history, membership structure, avalanche education and the unique challenges of being a software provider. CAA members may work in any number of different facets of the snow and avalanche world, from guiding to education, patrolling to avalanche forecasting, and for operations such as ski resorts, heli, cat or ski touring operations and industrial or transportation settings such as mines, pipelines, highways or railway. This broad set of avalanche practitioners are united by a common training stream, a daily information exchange, and a common standard of practice. In large part this has all been coordinated by the Canadian Avalanche Association Eirik is a long-time avalanche professional based in Whitehorse, Yukon. Originally from Norway, he grew up skiing backcountry and has worked in the snow for 18 years as a researcher, forecaster, educator, consultant, and ACMG ski guide. He has an M.Sc. in GIS with research focused on applications of machine learning to avalanche mapping. He currently works on the Alpine Solutions Avalanche Services engineering team, specializing in terrain modelling and avalanche risk assessment. However, he still gets out into the field to support industrial operational avalanche risk management programs as much as he can through the winter. Eirik is passionate about supporting, promoting, and elevating professional avalanche practice in Canada; he worked for ten years as an instructor with the Canadian Avalanche Association's industry training program and has served as President of the CAA since 2022. Music for this episode by Gravy @gravy.tunes Episode produced by Wes Gregg at Trigger Backcountry Adventures www.avalancheassociation.ca www.wyssenavalanche.com www.gordini.com www.beaconguidebooks.com

Join us on the Newborn Screening SPOTlight podcast with Dr. Jerry Vockley, who is a Professor of Human Genetics, the Graduate School of Public Health, Cleveland Family Endowed Pediatric Research, School of Medicine, Chief of Genetic and Genomic Medicine, UPMC Children's Hospital of Pittsburgh, and Director of the Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh.    Dr. Vockley is internationally recognized as a leader in the field of inborn errors of metabolism. His current research focuses on mitochondrial energy metabolism, novel therapies for disorders of fatty acid oxidation and amino acid metabolism, and population genetics of the Plain communities in the United States. He has published over 320 peer-reviewed scholarly articles and is the principal or Co-investigator on multiple NIH grants. Dr. has an active clinical research program and participates in and consults on multiple gene therapy trials.   Dr. Vockley has served on numerous national and international scientific boards including the Advisory Committee (to the Secretary of Health and Human Services) on Heritable Disorders in Newborns and Children where he was chair of the technology committee. He is a Fellow in the American Association for the Advancement of Science. He is a Founding Fellow of the American College of Medical Genetics and Genomics, and currently serves on its board of directors. He is founder and chair of the International Network on Fatty Acid Oxidation Research and Therapy (INFORM). He has served as chair of the Pennsylvania State Newborn Screening Advisory Committee and is a past president of the International Organizing Committee for the International Congress on Inborn Errors of Metabolism and the Society for the Inherited Metabolic Disorders (SIMD). On this podcast, Dr. Vockley shares his career journey and personal stories about the impact of newborn screening research on physicians, families, and advocates.  Interview Questions: Among your many appointments, you serve on the Board of the American College of Medical Genetics and Genomics (ACMG) and advise on efforts to improve health through the practice of medical genetics and genomics. In addition to the ACMG board, you were integral in the early and current days of the NBSTRN. Can you tell us how you got involved in NBSTRN? As technologies to screen, diagnose, treat, and manage disease advance and increasingly use sequencing, can you share with our listeners your vision of how sequencing will be used in newborn screening in the future? What excites you about this potential, and can you share any concerns? You have published over 320 peer-reviewed scholarly articles and led many efforts funded by NIH and others. Can you describe the key findings from your most recent publication, “Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder.” You are the Cleveland Family Endowed Pediatric Research, School of Medicine Professor of Human Genetics, Graduate School of Public Health, and the Director of the Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh. In your article titled “Scaling genetic resources: New paradigms for diagnosis and treatment of rare genetic disease,” you mentioned that the movement from the basic science laboratory to clinical trials is still hampered by a regulatory system rooted in traditional trial design and requires a fresh assessment of safe ways to obtain approval for new drugs. You proposed the development and scaling of nucleic acid-based therapies. Could you share this possibility with our listeners and what challenges need to be overcome to deliver them safely with appropriate evaluation and long-term follow-up? Can you share any stories of inspiration that keep you going? Anything else you'd like to share? Thank you for your efforts in conceptualizing the NBSTRN and establishing a network of stakeholders that includes health professionals, researchers, state programs and families, and advocates. Do you have advice for this community and how they can help to realize and capitalize on the fifteen years of NBSTRN? You are involved in training the new generation of medical geneticists. What do you tell them about newborn screening research? What does NBS research mean to you?  

This week we have a bunch of shows to talk about including BAKI: Son of Ogre (on Netflix), thoughts on the series finale of Secret Invasion (Disney+), and other news in the world of ACMG. Then in our TOP TOPIC of the WEEK I give my thoughts on TWISTED METAL the series (on Peacock) in hopes that they gave fans exactly what they want. Did they? All this and more in this edition of A.C.M.G. presents TALK TIME LIVE!

Will Gadd is one of the top adventure athletes in the world (Outside, Men's Journal and Explore). He is best known for wild outdoor adventures in multiple different sports, but he's most proud of his ability to complete those adventures safely and share them with others. He has appeared in, hosted or produced more than 100 global television projects. He is an award-winning writer, film maker, and dad (no awards yet). His book on ice climbing is the top publication in its field, and has been translated into five languages. Gadd's presentations on "Risk and Reward" and related topics take him all over the world to speak to audiences ranging from Nike and Enbridge to at-risk youth . He is a National Geographic " Adventurer of the Year" and recently became the first person to climb a frozen Niagara Falls. Last winter he used his ice climbing skills to find new life forms under a glacier, a world first, and just returned from a major TV production on the last ice in Africa. He is an ACMG guide, and uses way too much spice in his cooking. https://willgadd.com Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode, we are exploring limb-girdle muscular dystrophy (LGMD). Joining us for this conversation are two experts, Dr. Louise Rodino-Klapac, and genetic counselor Livija Medne.Dr. Louise Rodino-Klapac is the Executive Vice President, Head of R&D and Chief Scientific Officer at Sarepta Therapeutics who has 15 years of experience researching and studying LGMD. She is renowned for her work in molecular genetics and gene therapy. Her pioneering research is the foundation for five of our investigational limb-girdle muscular dystrophy (LGMD) programs. Hear from Dr. Rodino-Klapac about LGMD, the importance of knowing your subtype and the basics of gene therapy!Livija Medne is a Senior Genetic Counselor and Systems Director of Genetic Counseling at the Children's Hospital of Philadelphia. She has 15+ years of experience in pediatric neuromuscular diagnoses, including LGMD. She co-chairs and is one of the course directors of the Curriculum Committee at the University of Pennsylvania Genetic Counseling Program. In addition, Livija is an advocate for the professional development of junior genetic counselors, having co-founded the first Genetic Counselor Mentorship committee at CHOP.On This Episode We Discuss:Limb-girdle muscular dystrophy (LGMD)Which muscles are typically are affected first Symptoms that individuals with LGMD experience and when symptoms usually startThe prevalence of LGMD compared to Duchenne Muscular DystrophyHow people are diagnosed with LGMDWhy genetic testing is important to determine specific subtypes of LGMDGene therapy programs for the most common subtypesThe goal of the gene therapyWhen FDA-approval for LGMD gene therapy can be expected How patients can gain access to the gene therapy program and how health care providers can refer patientsBusting myths about LGMD If you'd like to take a deeper dive after listening to today's episode, follow these links to learn more about limb girdle muscular dystrophy, gene therapy, and genetic testing for LGMD. You can also visit raregenomes.org and limbgirdle.com to learn more! And be sure to follow Dr. Louise Rodino-Klapac on Twitter!You can also check out this installment of the PhenoTips Speaker Series to hear Kira interview Livija Medne about genetic counselors in leadership positions. Stay tuned for the next new episode of DNA Today on March 10th, 2023! New episodes are released every Friday. In the meantime, you can binge over 225 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. Our Outreach Intern is Sanya Tinaikar. Our Social Media Intern is Kajal Patel. And our Graphic Designer Ashlyn Enokian.See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNAToday.com. Questions/inquiries can be sent to info@DNAtoday.com. Which muscular dystrophy causes weakness of the muscles typically starting around the hips and shoulders? That would be limb girdle muscular dystrophy, or LGMD. LGMD is a group of neuromuscular diseases caused by mutations in genes responsible for proteins critical for muscle function, regulation, and repair1-3. Sarepta is a global biotechnology company working on engineering precision genetic medicine with the goal of changing the lives of people living with rare muscular dystrophies. Their multi-platform Precision Genetic Medicine Engine includes gene therapy, RNA and gene editing approaches. Oh that reminds me, ACMG is in March and Sarepta will be at booth 504. You can also head over to limbgirdle.com to learn more. (Sponsored) 1. Murphy AP and Straub V. J Neuromusc Dis. 2015;2(suppl. 2):S7-S19.2. Liewluck T and Milone M. Muscle Nerve. 2018;58(2):167-77.3. McNally EM. The Sarcoglycans. In: Landes Bioscience. 2000–2013.Surely you have heard of whole genome sequencing, but what about rapid and ultra-rapid whole genome sequencing? This is an emerging method of diagnosing genetic conditions for quick management. PerkinElmer Genomics offers this incredibly valuable test, which can be life saving for ill babies and kids. Learn more in our full episode (#226) with PerkinElmer Genomics. You can visit perkinelmergenomics.com for more information. (Sponsored)Surely you have heard of whole genome sequencing, but what about rapid and ultra-rapid whole genome sequencing? This is an emerging method of diagnosing genetic conditions for quick management. PerkinElmer Genomics offers this incredibly valuable test, which can be life saving for ill babies and kids. Learn more in our full episode with PerkinElmer Genomics on here, DNA Today! You can visit perkinelmergenomics.com for more information, the link is also available in the show notes and on our website DNAtoday.com. (Sponsored)I've enjoyed recording a few episodes about epigenetics, one of the interviews where I learned the most was with the Diagnostic Labs at the Greenwood Genetic Center. They taught me about EpiSign which is a novel clinically validated test that analyzes methylation. I just learned that since this episode in 2021, verison 4 of EpiSign has been released which has expanded to include over 70 conditions. If you are attending ACMG this month stop by booth 607 to chat with Greenwood Genetics. In the meantime brush up on your epigenetics by listening to Episode #145 of DNA Today and visit GreenwoodGeneticCenter. (Sponsored)

Can rapid whole genome sequencing (WGS) be utilized in the NICU setting? We explore in this podcast episode! Joining us for this episode is Dr. Hong Li, a clinical geneticist at Emory University. Our other expert is a recurring guest, world-renowned geneticist Dr. Madhuri Hegde. She serves as the Senior Vice President and Chief Scientific Officer of Global Lab Services at PerkinElmer Genomics, a global leader in genetic and genomic testing focused on rare diseases, inherited disorders, newborn screening, and hereditary cancer.If you want to hear her on other episodes of DNA Today tune into Episode 177 where we nerded out about the power of whole genome sequencing (which is a great precursor to this conversation) and Episode 202 about Duchenne Muscular Dystrophy.In addition to her role at PerkinElmer, Dr. Hegde is also a board certified diplomate in clinical molecular genetics by the American Board of Medical Genetics, and an ACMG Fellow. Previously, she was the Executive Director of Emory Genetics Laboratory. She received a B.Sc. and M.Sc. from the University of Bombay and a Ph.D. from the University of Auckland. She completed postdoctoral studies at Baylor College of Medicine.Dr. Hong Li is a clinical and biochemical geneticist at Emory University School of Medicine who is passionate about diagnosing and treating children and families with genetic and metabolic diseases. She also oversees the Emory Metabolic Clinic, serves as Co-Chair of the Georgia Newborn Screening Advisory Committee (NBSAC), where she is extensively involved in Georgia's NBS development, implementation, and clinical follow-up for children with metabolic disorders, is the Vice-Chief of the genetics section at Children's Healthcare of Atlanta and geneticist of the multidisciplinary differences of sex development (DSD) clinic at CHOA and the site PI of the DSD translational research network (DSD-TRN). She also serves as the medical director of the Emory CTCF-related disorder (CRD) center.Dr. Li also holds multiple educational roles, including sponsoring the first Emory Genetics Interest Group at Emory College and School of Medicine to foster interest and attract intelligent students to join the growing field of medical genetics! Her research interests are primarily devoted to exciting clinical trials for genetic/metabolic diseases, and she is the principal investigator for multiple Phase I/II and III clinical trials. She is also interested in new gene discovery and better defining the phenotype of rare genetic diseases.On This Episode We Discuss:Symptoms that would warrant immediate genetic testing after birthStarting with whole genome sequencing (WGS) versus exomeOther tests that are useful for babies in the NICU beyond the genomeHow laboratories are maximizing the genome data for babies in a medical crisisSamples used for urWGS (ultra rapid WGS) and newborn screeningTrio testing with parents to rule out variants of being causative of symptomsurWGS minimizing healthcare costsWhy timing is so important for babies in the NICUHow results from urWGS can influence treatment plansHow projects like Project Baby Bear and Project Baby Deer are paving the way for whole exome sequencing as part of newborn screening Here is an interesting article from PerkinElmer about expanding into ultrarapid whole genome sequencing. During the interview Kira mentioned two episodes about the Telomere to Telomere Consortium which officially finished the complete human genome sequence in 2022. Dr. Eric Green shares his expertise in Episode 183 followed by Dr. Miga and Dr. Phillippy in Episode 184. Stay tuned for the next new episode of DNA Today on Friday, March 17th when muscular dystrophy experts Dr. Louise Rodino-Klapac (from Sarepta) and Livija Medne (Children's Hospital of Philadelphia aka CHOP) share their expertise specifically about limb-girdle muscular dystrophy. New episodes are released every Friday. In the meantime, you can binge over 225 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. Our Outreach Intern is Sanya Tinaikar. Our Social Media Intern is Kajal Patel. And our Graphic Designer Ashlyn Enokian.See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNAToday.com. Questions/inquiries can be sent to info@DNAtoday.com. Surely you have heard of whole genome sequencing, but what about rapid and ultra-rapid whole genome sequencing? This is an emerging method of diagnosing genetic conditions for quick management. PerkinElmer Genomics offers this incredibly valuable test, which can be life saving for ill babies and kids. You can visit perkinelmergenomics.com for more information. (Sponsored)If you've been listening to DNA Today for a while, you probably know I am also a full time prenatal genetic counselor. Between that job, this podcast, and being a producer/host of other podcasts, I am pretty busy! To keep my energy up and stay productive I drink a decent amount of coffee. The new coffee I'm drinking is from Four Sigmatic. I'm really picky about my coffee, it's got to be bold, not watery. And I've been really happy with Four Sigmatic. Here's the difference from other coffees, it includes mushrooms, which I know sounds bizarre. I will admit I was hesitant, but you get health benefits and don't taste it. I like the immune system boost, as I often get sick in the winter months. So we teamed up with Four Sigmatic to get you 30% off using promo code “DNATODAY” redeem it at FourSigmatic.com, again that's FourSigmatic.com using code “DNATODAY” for 30% off! And let me know if you like it too! (Sponsored)I've enjoyed recording a few episodes about epigenetics, one of the interviews where I learned the most was with the Diagnostic Labs at the Greenwood Genetic Center. They taught me about EpiSign which is a novel clinically validated test that analyzes methylation. I just learned that since this episode in 2021, verison 4 of EpiSign has been released which has expanded to include over 70 conditions. If you are attending ACMG this month stop by booth 607 to chat with Greenwood Genetics. In the meantime brush up on your epigenetics by listening to Episode #145 of DNA Today and visit GreenwoodGeneticCenter. (Sponsored)Which muscular dystrophy causes weakness of the muscles typically starting around the hips and shoulders? That would be limb girdle muscular dystrophy, or LGMD. LGMD is a group of neuromuscular diseases caused by mutations in genes responsible for proteins critical for muscle function, regulation, and repair1-3. Sarepta is a global biotechnology company working on engineering precision genetic medicine with the goal of changing the lives of people living with rare muscular dystrophies. Their multi-platform Precision Genetic Medicine Engine includes gene therapy, RNA and gene editing approaches. Oh that reminds me, ACMG is in March and Sarepta will be at booth 504. You can also head over to limbgirdle.com to learn more. (Sponsored) 1. Murphy AP and Straub V. J Neuromusc Dis. 2015;2(suppl. 2):S7-S19.2. Liewluck T and Milone M. Muscle Nerve. 2018;58(2):167-77.3. McNally EM. The Sarcoglycans. In: Landes Bioscience. 2000–2013.

In this installment of The Avalanche Hour Podcast; Wes Gregg interviews Erin Tierney the President of the CSGA as the second installment of the 'Who is the ACMG? Who is the CSGA? Erin has worked in the avalanche industry since 1997 mainly as a heli ski guide and instructor for the CSGI. Lately she has enjoyed exploring the different arms of the avalanche industry as a forecaster, avalanche tech and now as an instructor for the CAA ITP program. Erin lives in Mount Currie, BC with her family. Find out more about the CSGA/CSGI: canskiguide.com Facebook: Canadian Ski Guide Association president@canskiguide.com Music in this episode is used with permission of the artist, Age Diamante - Chakra Tonic Artwork by Mike Tea, miketea.com Episode produced by Wes Gregg

In this episode, Wes Gregg has a chat with ACMG Technical Director, Mike Adolph. This conversation is based on the concept of providing listeners an opportunity to hear directly from the source how the Technical Assessment Program works and the history of the ACMG. Mike Adolph is a ACMG/IFMGA Mountain Guide and also the current ACMG Technical Director. He's currently residing in Alberta splitting his time between Red Deer, his kids attend a Spanish school there and Nordegg. Mike tries to maintain a diverse winter guiding background that includes some mechanized skiing, ski touring, ice and alpine climbing as well as working as instructing in the ACMG training and assessment programs winter courses. He has been working as a guide for 25 years and completed his mountain guide certification in 2007. Skiing with his wife and two kids takes up a lot of free weekends during the winter months and is pleased to say that he's had several opportunities to ski first tracks at the local hill in Red Deer. ACMG Mission Statement: The ACMG's mission is to protect the public interest in mountain travel and climbing instruction by: Developing and administering rigorous standards for certification and professional conduct; Aiding the professionalism of its members through public advocacy and program delivery; and, Training and assessing future guides and instructors to the highest standards of risk management. web links: www.acmg.ca Association of Canadian Mountain Guides About the group. Courses and certification programs offered. Technical tips. List of certified guides. (professional association of trained and certified guides and instructors) www.acmg.ca ACMG training and assessment program - Movement screening dates and locations can be found here ACMG Course Dates and Fees (tapacmg.ca) ACMG Course Dates and Fees - tap@acmg.ca People can also find Mike at: www.viaferratacanada.com (He's built 2 ferratas in his local range) Alberta Via Ferratas | Via Ferrata Canada Via ferrata climbing for everyone in the David Thompson Rocky Mountains. Get info and guides for the Nordegg area Via Ferratas. www.viaferratacanada.com COE.ca - Rock & Ice Climbing Guiding and Courses, Youth Programs, and Retreats in the Canadian Rockies. Courses and Guiding for rock, ice and alpine climbing as well as kayaking and caving. www.coe.ca Music in this episode is used with permission of the artist, Age Diamante - Chakra Tonic Artwork by Mike Tea, miketea.com Episode produced by Wes Gregg

Listen to Dr. Wendy Chung, a board-certified clinical and molecular geneticist with over 20 years of experience in human genetic research, share her story.  Her team has led ground-breaking research describing the genetic basis of both rare and common genetic diseases, and the development of precision therapies based on the genetic findings in individuals. She was a part of the two-year pilot of newborn screening for Duchenne Muscular Dystrophy and is currently leading the GUARDIAN STUDY, which has a goal of genome sequencing 100,000 newborns in NYC. She is currently the co-Chair of NBSTRN Steering Committee, which has informed the evolution of the tools and resources for newborn screening research. Podcast Interview: Dr. Chung, you are a board-certified clinical and molecular geneticist with 20 years of experience in human genetic research. How did you get involved with newborn screening research? Your work has led to ground-breaking publications describing the genetic basis of both rare and common genetic disease, and your efforts have often described not only the basis for disease, but the development of precision therapies based on the genetic findings in individuals. You are now leading a new effort, the Guardian Study. Please tell our audience how your years of research led you to conceive of and undertake this effort. NBSTRN highlights innovative efforts at our annual NBS Research Summit. You presented in 2020 on the "Genomic Causes of the Broken Hearts” Can you describe your goals with this effort and how this could facilitate early treatment and improve health outcomes for infants with congenital heart disease? Your research team collaborated with ACMG and NBSTRN, and many others in a two-year pilot of newborn screening for Duchenne Muscular Dystrophy. Could you share with our listeners what you and the consortia learned from this pilot and how this might inform future efforts? In 2019 the NBSTRN Bioethics and Legal Workgroup led a published recommendations to guide pilot studies and included a recommendation to enroll diverse participants. Informed by this work, your team examined parental views about expanded NBS and the use of genomics. Please tell what this effort told you about the role of parental choice in expansion of NBS. Are you involved in training the next generation of board-certified clinical and molecular geneticist and what do you tell them about newborn screening research? Thank you for serving as co-chair of the NBSTRN Steering Committee. What are you most excited about? What role could NBSTRN play in your efforts in advancing NBS research? In addition to funding NBSTRN, NICHD supports a variety of efforts to advance NBS research. CDC and HRSA also fund important efforts to advance and support NBS through work with state NBS programs, policy makers, parents and advocates. Please share your vision of how these key federal partners could work together to accelerate the translation of research findings into public health and clinical care. What does NBS research mean to you?    

The retina is a thin layer of tissues, cells, and nerves that line the back wall inside the eye.  This layer has millions of light sensing cells that receive and organize visual information according to the Mayo Clinic.On this Ask the Mayo Mom edition of the Q&A podcast, host Dr. Angela Mattke is joined by Dr. Brittni Scruggs, an ophthalmologist at Mayo Clinic Children's Center. Dr. Scruggs is a physician, surgeon, and scientist with a research laboratory at Mayo Clinic studying gene therapy and stem cell therapy for retinal degenerations, including for children. She treats all ages, ranging from newborns to adults. Dr. Scruggs is a member of the national workgroup developing ACMG evidence-based guidelines for diagnosis and clinical management of inherited retinal diseases. Dr. Mattke and Dr. Scruggs explore retinal issues in children and discuss eye safety and health. 

This week we have Tim Ricci on the podcast to talk about how to get outdoors in winter.  Tim is an ACMG mountain guide at Yamnuska Mountain Adventures, and he shares his tips about avalanche training, ski touring, snowshoeing, ice climbing, and winter hiking. He even shares a bit on the arduous process to become a certified alpine mountain guide in Canada, which can take up to 8 years of training and testing! During the podcast talks about AST 1, AST 2, Intro to Backcountry skiing, Intro to Ice climbing and more great winter trips!

Dr. Lora Bean gives an overview of phenotypically-driven clinical results in this episode of DNA Today!Dr. Lora Bean is a clinical molecular geneticist who currently serves as the Senior Director of Quality Assurance at PerkinElmer Genomics. Dr. Bean has expertise in traditional clinical molecular testing as well as newer techniques such as next generation exome and genome sequencing. She has served as a molecular editor for GeneReviews and as a member of the American College of Medical Genetics Laboratory QA / QC Committee, an item writer for the ABMGG, and is currently a laboratory inspector and a Biochemical and Molecular Genetics Committee member for the College of American Pathologists. Previously, she served as an Associate Professor in the Department of Human Genetics and Senior Director and Regulatory Director of the EGL Genetics (formerly Emory Genetics Laboratory) Molecular Diagnostic Laboratory. Dr. Bean earned her PhD in the Department of Human Genetics at Case Western Reserve University and completed a postdoctoral fellowship at Emory University. She is board-certified by the American Board of Medical Genetics and Genomics and a fellow of the American College of Medical Genetics. On This Episode We Discuss:Differences between gene panels, exome, and genome sequencing Adapting workflows from exome to genome utilizing existing frameworksAdvantages of different types of testingLimiting the floodgates of variants that inevitably come with whole genome sequencingHelpful information for providers to include with specimens to guide the laboratory when the data are analyzedThe role of phenotypic data specifically in classification of sequence variantsDeep intronic variantsKira was off by one, but Dr. Bean was right, ACMG has 73 genes on the list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). If you found the topics that we discussed on this episode interesting, check out this recorded presentation from Dr. Bean entitled, “Why Bigger Isn't Only VOUSier.”Learn more about phenotypically-driven clinical results at PerkinElmerGenomics.com and follow them on Twitter, Facebook, and LinkedIn. Stay tuned for the next new episode of DNA Today on October 21st, 2022! New episodes are released on Fridays. In the meantime, you can binge over 205 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNAToday.com. Questions/inquiries can be sent to info@DNAtoday.com. When Willow was diagnosed with Multiple Sulfatase Deficiency (MSD), her mother, Amber was told to love and care for Willow but that there was no cure for this terrible fatal condition. Amber set out to find and fund the cure for MSD. That's when she started the United Multiple Sulfatase Deficiency Foundation. She shares this personal experience on Episode 205 of DNA Today including how this affected her family and the relationships she has built with other families in the MSD community. (SPONSORED)TrakGene has designed a genetics electronic health record. Here's what it features: pedigrees, demographic data, genetics information, risk tools, and sophisticated reporting, all within a clinician designed workflow. It integrates with other clinical genetic software, databases, and hospital information systems to maintain accurate patient records.Go check it out at TrakGene.com. And keep your eye out for our full episode interviews with TrakGene coming soon to DNA Today. (SPONSORED)

October 2022: A points to consider statement of the ACMG

SummaryIn today's episode, we sit down with Catherine Pitura an ACMG apprentice rock guide and the founder of Mind Tools. Catherine as she puts it “is just a person with a big climbing experience”. Like so many of us, she fell quickly in love with the sport of climbing, but, unlike many of us, she had the opportunity to live the dirtbag dream. For nine years she lived and breathed climbing. During this time, she became a capable trad leader and certified apprentice rock guide. Towards the end of this nine-year climbing cycle, she started to feel that there were things about her life and herself that had been neglected. That there might be more to life than being fully immersed in climbing. So she began her dirtbag rehab, where she journeyed back into “everyday life” and worked on exploring the intricacies of the human mind. Now, she has combined her experience as a climber and the knowledge she obtained through her dirtbag rehab into a business called “The Conscious Climber” and developed an innovative product named “Mind Tools”. In our conversation, we dive deep into what it's like to return to life after living the dirtbag dream, the effect that climbing has on the mind, the relationship between our conscious and subconscious minds, and finally how we can use mind tools to help us stay present, calm, and collected while in the vertical world. Please rate, review the show, and share this podcast with your friends. Word of mouth is one of the most powerful tools to help us out. Contact us:IG: @the.climbing.majorityEmail: theclimbingmajoritypodcast@gmail.comReferencesCody Bradford MemorialPurchase Mind Tools HEREMind Tool Reviews https://www.vernonmorningstar.com/business/mind-over-matter-vernon-entrepreneur-creates-motivational-rock-climbing-gear/https://gripped.com/events/watch-free-talk-by-mind-tools-for-climbers-on-april-21/https://gripped.com/gear/mind-tools-aim-to-keep-you-psyched/Follow Catherine Pitura: @climbingcovers @theconsciousclimber

Today we feature Tamar Goldwaser and the New ACMG Guidelines for Prenatal and Preconception Carrier Screening. Genetic testing is expensive! Until now it has been reserved for a few populations that are known to be at higher risk. But we have missed many carriers this way. Many families continue to be unprepared for the news that their child has a severe inherited genetic condition that was passed on from the parents. What about everyone else? The time is now! With advanced technology making testing for hundreds of genes all at once, faster and cheaper, we can finally envision a reality where all patients can be tested before they start to build a family. If a couple finds out that they are carriers, they can use this information to take advantage of various reproductive options. This is genetic testing for all! This is one step towards equity in reproductive medicine. I am proud to be an author on a Practice Resource published by the American College of Medical Genetics and Genomics (ACMG) entitled “Screening for autosomal recessive and X-linked conditions during pregnancy and preconception,” which recommends a uniform set of conditions for carrier screening panels for all individuals, regardless of ethnicity, race or population. It is my hope that this leads to increased awareness, familiarity and clarity among doctors and genetics professionals and also puts pressure on insurance companies to cover testing.

It's time for another episode of the Austrian Association for Snow and Avalanches @oegsl. Guest hosts Matthias Walcher and Anna Heuberger chat with the “Wayne Gretzky of guiding” RUDI KRANABITTER - an Austrian mountain guide who spent many years working in Canada and became an honorary member of the ACMG, as well as ALBERT LEICHTFRIED, meteorologist, ex-pro ice climber, mountain guide and technical director of the Austrian mountain guides training program. What are the differences between Canada and Austria when it comes to snow and avalanche training and mentality? What can we learn from each other? Music: "Milk" by Ketsa

Brandon Gulstene is an aspiring ski guide from Banff, Alberta. From summer camp to ski patrolling to the ACMG, this episode is packed with experiences and research on how we can make the backcountry and mountain guiding a more inclusive and welcoming space, normalize mental health in the mountains, and [...] The post Big Stick Energy – E14 – Mental Health and Ski Guiding – Brandon Gulstene appeared first on Out Of Collective.

On January 1, 2022, the New York Times published an article focused on the high false positive rates of micro-deletions and -duplications in non-invasive prenatal screening tests NIPS/NIPT. The article was entitled, “When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong.” The reaction on Twitter from genetic counselors was mostly negative and critical. I discussed this article and genetic counselors' reaction to it with certified genetic counselor Katie Stoll. Articles/Podcasts Discussed: Kliff, Sarah and Aatish Bhatia. “When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong.” New York Times, January 1, 2022. “An Investigation into Flawed Prenatal Tests: How screening for chromosomal abnormalities that promised ‘peace of mind' instead caused anguish and confusion.” The Daily Podcast, New York Times. January 4, 2022. Katie's tweet related to genetic counselors' backlash to the article on Twitter. Related Articles and Resources: Skoto, et al. “Adherence of cell-free DNA noninvasive prenatal screens to ACMG recommendations.” Genetics in Medicine. April 3, 2019. Table of adherence to 2016 ACMG guidance for NIPS laboratories. Prenatal Information Research Consortium. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. October 2020. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics Landucci, Kelly. “NIPS: More Than Just a Sex Reveal.” Grey Genetics News Corner. April 22, 2019. Find Katie on Twitter @katie_stoll, LinkedIn, and on The DNA Exchange. Do you have questions or topics you'd like a genetic counselor to discuss on a future episode ? Leave us a short voice message here! We may use your message on a future show. Are you looking for genetic counseling? Grey Genetics is an independent telehealth genetic counseling and consulting company. Book an appointment with a genetic counselor specialized in your area of concern. All genetic counseling appointments take place over secure, HIPAA-compliant video-conferencing or by phone. Grey Genetics on Twitter: @GreyGenetics Grey Genetics on Instagram: @greygenetics Grey Genetics on LinkedIn

Episode 16 - Christine Feleki is Canada's first woman to be certified as an ACMG snowboard guide. Told she'd be better on skis, Christine simply knuckled down and proved that she could pass all the necessary assessments on her split. She started off working in various BC restaurants and cafes, to gain slope time, before beginning her 10 year journey from kitchen porter to guide. We chat guide culture, reshaping expectations and Christine talk us through the various hurdles you need to jump to become a ACMG guide. Christine rides for Phantom, Arc'teryx, Pallas Snowboards and Trinsic Optics Photo Credit Robin O"Neill

Christina Lustenberger, aka Lusti, is an all-around badass in the mountains.  Before this certified ACMG guide was killing it in the TGR movies, she was a racer out of Canada and paid for it with 5 full knee re-constructions over 10 years.  But even with the injuries, Christina competed in the Olympics and transitioned from race to guide school.  On the show we talk racing, guiding, being a woman in a male dominated world, malfunctioning gear and what it took for Lusti to earn the pro skier dream. Christina Lustenberger Show Notes: 3:30:  Huge amounts of energy, raised at the mountain by ski bums, and no television 7:00:  Ski racing with Ian Macintosh, moving up the ranks, graduating into the ski team, and having a DNF ski style 14:00:  Injuries, recovery, the Olympics, retiring from racing and becomng a guide 19:00:  Stanley:  Get 30% off site wide with the code drinkfast Peter Glenn Ski and Sports:  Over 60 years of getting you out there 10 Barrel Brewery:  Buy their beers, they support action sports more than anyone 21:30:  Black Crows, skiing with strangers, being a more educated woman in a male dominated world, and having a voice in the mountains 29:00:  Children of the Columbia, is there pressure at TGR, traveling far for bad conditions, and then getting hurt 35:00:  Getting fixed fast, first descents, and avalanche 38:30:  Dragon:  Get new goggles and really see the mountain use the code Powell15 to save 15% Alpine Vans:  Upgrade your adventure, Upgrade your life Elan Skis:  Over 75 years of innovation that makes you better 41:00:  Reacting to the slide, not getting a signal, calling in the cavalry, and the aftermath of the product failure 48:00:  Covid, sponsors, and Mount Nelson 56:00:  Inappropriate Questions with Ian Macintosh

Myriad Oncology Live episodes are recordings of an open-forum webinar hosted by Dr. Thomas Slavin. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, visit myriad-oncology.com/myriad-oncology-live for a list of dates, times, and subjects.

Three experienced women from the Canadian Avalanche industry sit down with guest host Dom Baker for a conversation about parenting and motherhood as an avalanche worker. Lisa Paulson is an ACMG mountain guide – the 8th female fully accredited ACMG mountain guide in Canada. She works as a Visitor Safety Specialist for Parks Canada, doing technical rescue as well as highway and public avalanche forecasting. When time allows, she guides both mechanized skiing and ski touring, as well as teaches both recreational and professional level avalanche courses. Lisa lives in Banff with her family, that includes two kids launching into the teen years! Wren McElroy is currently a lead forecaster with 6 Point Engineering on the Kemano T2 project in Northwestern BC. Wren has taught both recreational and professional avalanche courses and previously was the Snow Safety Supervisor at Whitewater Ski Resort in Nelson, BC. Wren is mom to Conrad, 21 River, 17 and stepmom to Jack 13. Bree Stefanson is an Avalanche Technician with the BC Ministry of Transportation Bear Pass Avalanche Program based in Stewart, BC, as well as a SAR Manager with Stewart Search and Rescue. Prior to this role she did other highways avalanche work, as well as industrial avalanche work throughout northwestern BC. Bree got her start in the avalanche patch as a pro patroller at Castle Mountain Resort. She is also a former CARDA avalanche dog handler. Bree lives in Stewert with her family, including a young daughter. Music in this episode used with permission from the artist - Age Diamante "I Do Love You" Produced by FBRrecording - Wes Gregg The Avalanche Hour Podcast logo designed by Mike Tea The Avalanche Hour Podcast is made possible with the support from: Wyssen Avalanche Control 10 Barrel Brewing Interwest Insurance

Today, Laura speaks with Barbara Harrison, Assistant Professor at Howard University (and 2020 NSGC Natalie Weissberger Paul National Achievement Award winner) and Katie Stoll, executive director of Genetic Support Foundation, about the new guidelines from ACMG on expanded carrier screening: how these changes move the field forward, and how they fall short.

The National Society of Genetic Counselors' (NSGC) 40th annual conference occurred virtually this past week. In this special extended installment of DNA Today we are recapping and reflecting on a few sessions from the conference. You can also check out our recap episodes of 2020 and 2019. Guests Laura Hercher has been a genetic counselor for nearly two decades. She is also the host of fellow genetics podcast, The Beagle Has Landed. She is a faculty member and director of student research at the Joan H. Marks Graduate Program in Human Genetics at Sarah Lawrence College, the country's first and largest training program for genetic counselors. Hercher is a writer and commentator with publications including articles in Wired, Aeon and Scientific American as well as peer reviewed journals. She is a co-founder of the DNA Exchange, a blog for the genetic counseling community founded in 2009, which has grown to over 100,000 views in 2017.Sally Rodríguez is a licensed and board-certified genetic counselor who specializes in the area of reproductive genetics, with expertise in expanded carrier screening (ECS), noninvasive prenatal screening (NIPS), and preimplantation genetic testing (PGT). Sally was an early-stage employee at Recombine, a genetic testing laboratory focused on reproductive genetics, and developed and managed the lab's ECS and NIPS offerings through the company's acquisition by CooperSurgical. Currently, she serves as a genetic counselor at Sequence46, a PGT laboratory. She received her Bachelor's degree in Molecular Biology from Princeton University in 2009 and her Master's degree in Genetic Counseling from The Johns Hopkins University Bloomberg School of Public Health in 2013. Sally is an active member of NSGC, the American Society for Reproductive Medicine (ASRM), and the Minority Genetics Professionals Network (MGPN).NSGC 2021 Conference Session OD01: Advocating for Autonomy: Genetic Counselors as Champions for Comprehensive Reproductive Health with Laura Hercher Overview of Texas SB 8 (Abortion Ban) Texas SB 8 disproportionately affecting pregnant peopleRepercussions on genetic counseling from Texas SB 8National impact on Texas SB 8Jackson Women's Health Organization vs DobbsIncrease in abortion laws vs public opinion Defining abortion reason bansTo learn more about abortion law from Laura Hercher, check out The Beagle Has Landed her podcast episode with Jordan Brown. NSGC 2021 Conference Session B03: The Devil is in the Details: Race-Based Medicine and Healthcare Disparities in Genetic Counseling with Sally RodríguezComparing race/ethnicity based vs panethic carrier screening How laboratories use ethnicity in carrier screening Pitfalls of race/ethnicity based testingIssue with self-reported race/ethnicitySelf-reported race vs genetic ancestry Calculate carrier residual risk of being a carrier based ethnicity Cause of disparities in residual risks Testing for genetic ancestry as part of carrier screening ACMG updated practice guidelines Downstream effects of disparities in carrier screening How healthcare providers can solve carrier screening disparity issues Other NSGC 2021 sessions mentioned during the episode:C02: Prenatal Testing: When Multiple Technologies Reveal More than Meets the Eye LabCorp sponsored with case presentations by Samantha Caldwell, Lila Dayani, and Deanna HutchinsonC03: 2021 Janus Lecture: “You Can Never Feel My Pain”: The History and the Future of Sickle Cell Disease. Presented by Barbara HarrisonD02: The Routine Incorporation of Molecular Ancestry into Carrier Screening: Sema4's Clinical Experience. Presented by Lisa Edelmann and Audra Bettinelli Stay tuned for the next new episode of DNA Today this Friday on October 1st where we explore the genetics of ALS with Genomenon! New episodes are released on the first and third Friday of the month, with some bonus episodes like this one! In the meantime, you can binge over 150 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes in 2021 are also recorded with video which you can watch on our YouTube channel. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com. Do you or someone you know have Prader-Willi syndrome? Harmony Biosciences is looking for people with Prader-Willi syndrome to enroll in a new clinical study in the United States. Harmony Biosciences will be studying the safety and impact of an investigational medication on excessive daytime sleepiness, cognition, and behavioral function in people with Prader Willi syndrome. Learn more about the clinical study and refer a patient to a study center here. (SPONSORED)If you're a healthcare provider helping pregnant patients you have inevitably been asked the question, “Can I take this medication during my pregnancy”? Then you need TERIS, a clinical electronic resource that contains information on the teratogenic risks of over 1,700 medications and other environmental exposures and infections, including 200 of the most frequently prescribed drugs. What makes TERIS a unique database? TERIS is governed by an Advisory Board of world-renowned experts in clinical teratology and is an intellectual property of the University of Washington. Visit TERIS today for your free no obligation 2-week evaluation license. (SPONSORED)

In celebration of Batman Day this weekend (September 18th this year) I am reviewing BATMAN: The Long Halloween Part 2. Plus, news in the world of our favorite fandoms including thoughts on the trailer for the upcoming Marvel Studios series HAWKEYE as well as thoughts on the latest episode of Marvel's WHAT IF? featuring the return of Michael B. Jordan as Killmonger! All this and more as ACMG presents TALK TIME LIVE! 

Congenital anomalies (CA), developmental delay (DD), and intellectual disability (ID) are among the most common indicators in children that lead to genetic testing. Identification of an underlying diagnosis for CA or DD/ID can be consequential to care management and long-term prognosis for the child. But there has been no evidence-based guideline for clinicians to refer to that supports the use of exome or genome sequencing as a first-line or second-line test for the evaluation of pediatric patients with CA or DD/ID. On this month's GenePod, Fuki Hisama, MD, FACMG, FAAN and Murugu Manickam, MD, FACMG, who co-chaired the American College of Medical Genetics and Genomics (ACMG) evidence-based work group, discuss how a team of experts was brought together to provide the ACMG's first ever evidence-based clinical guideline. This guideline lays out clear recommendations for use of exome or genome sequencing in clinical care to optimize outcomes for pediatric patients with CA or DD/ID. “In a way, this model of an evidence-based guideline is creating the standard and a template for future studies” says Dr. Manickam. See acast.com/privacy for privacy and opt-out information.

This summer K2 will see a rare event, an attempt on the fully unclimbed West Ridge. Canadian Ian Welsted and American Graham Zimmerman will make an alpine attempt with no oxygen. While the route has been partially climbed three times, the final few hundred meters have never been completed for various reasons. They leave for Pakistan on June 17. After an extensive acclimatization program which may include climbing the 8000er Broad Peak, they hope to summit near the end of July. Ian and Graham have a long impressive history of difficult technical climbs. Graham has climbed the 7000-meters peaks including: Southwest Ridge of K6 West (7040m), Pakistani Karakoram North ridge of Changi tower (6500m), Pakistani Karakoram Northeast buttress of Mt. Laurens, Alaska Southeast Face of Link Sar (7041m), Pakistani Karakoram. He told me: The Karakoram is the mountain range that I find most inspiring. It is where I have seen some of my biggest success as an alpinist, and it is where I have learned some of my most important lessons.There is one peak in the Karakoram that literally stands above the rest, a peak that I have seen on the horizon from several different summits and has always attracted my attention, the majestic and steep 8611m Chogori, or K2. From the Canadian Alpine Club on Ian: Ian is best known in climbing circles as one of only two Canadians to be awarded the Piolets D'or, for his first ascent of K6 West (7000m) in Pakistan. Born and raised in Brandon Manitoba Ian moved to Chamonix France at the age of 17. From this year in the mountains he returned to Canada to attend Ottawa University and McGill University where he studied economics and philosophy. In his youth, Ian ski raced but was exposed to the full gamut of mountain pursuits in Chamonix. From skiing and snowboarding the backcountry powder of Nelson and Rogers Pass he moved to Canmore in 2005. Quickly integrating into the climbing community, he pursued waterfall ice climbing with 100 day winters before turning his attention to alpine first ascents. With this experience he began casting further afield and undertook expeditions to the Coast Range, Patagonia, Denali, to the Khumbu area of Nepal, and 3 trips to the Pakistani Karakoram. In 2016 Ian began the process of gaining ACMG certification so that he can share his experience gained over 25 years, and his love of the mountains. I was able to get Graham for an extensive interview on the climb. We cover a lot of topics including: His and Ian's history (both Piolet d'Or winners) The style of climbing The route And their plans on how to return from the summit and more Best of luck to Ian and Graham. Let's chat when you get back. Climb On! Alan Memories are Everything

Episode 62 Dark Starts backcountry splitboarding podcast presents Judson Wright, founder and owner of Kootenay Backcountry Guides. Started skiing early in life with his family in southern Ontario, taking trips to Vermont and eventually discovered snowboarding. Moved out West and fell in love with powder, following that passion he met a heli guide that inspired his current life path as a guide. Started Kootenay Backcountry Guides in 2017 and has been killing it with both the guiding and education parts of the business. While training to become an ACMG, Jud was caught in the middle of a slide on an extended traverse from Bugaboo to Rogers Pass. He shares the wild story with us as well as the humbling lessons that he learned. These important lessons are a strong foundation for the education that he provides to the community with both Kootenay Backcountry Guides training and the State of the Snowpack events that he supports in Nelson, BC. We learned so much about training, gear, and much more and hope you do too. Jud, it was truly our pleasure. Show links: https://kootenaybackcountryguides.com/ https://westonbackcountry.com/ https://www.roamshop.com/ https://www.stateofthesnowpack.com/ https://tributeboardshop.ca/ Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

  Hello, this is the “Newborn Screening SPOTlight”. This podcast is about the advancement of rare disease research told by health professionals, researchers, parents and advocates. This podcast is for you to learn how newborn screening research saves the lives of babies every day through discoveries of new technologies and treatments. You will hear stories from experts who treat babies, the families who care for them, and the researchers who make it all happen. We are your co-hosts, Dr. Kee Chan and Dr. Amy Brower. We are from the Newborn Screening Translational Research Network (also known NBSTRN).   Our work is supported by one of the institutes at the National Institutes of Health in Bethesda Maryland called the Eunice Kennedy Shriver National Institute of Child Health and Human Development (also known as NICHD).  We are from the American College of Medical Genetics and Genomics (also known as ACMG) and ACMG leads the NBSTRN.     Screening babies saves lives every day, and research advances newborn screening by developing new technologies to screen, diagnose and treat. NBSTRN helps accelerate research by creating tools, resources and expertise for researchers, doctors, families, patients and advocates.   To learn how you can help advance newborn research, advocate for rare disease screening and treatment, and learn about important discoveries, become a member of the Newborn Screening Translational Research Network by visiting our website at www.nbstrn.org.   Thank you for listening to this episode of Newborn Screening SPOTlight. If you like our podcast, please subscribe and share an episode with your colleagues, friends and family.     Get involved! Stay informed! Help us advance discoveries! Together, let's increase the impact of newborn screening research by listening to your stories.

Our guest today, Roger Yim, has over 430 weeks of leading and instructing wilderness-based expeditions, focusing on leadership, wilderness skills, personal development, environmental stewardship, and expedition behaviour. He started working in outdoor education in the early '90s. In 1996 Roger began working for the Canadian Outward Bound School, and it 98; Roger took his NOLS River Instructors course and work 18 years with the school. He mostly worked on ski, mountaineering, rock climbing, avalanche, and whitewater courses but has led several rock climbing caving and sea kayaking courses.  Now, Roger lives in Nelson, British Columbia and works as an ACMG ski guide in the winter. This summer, Roger is excited to return to NOLS, leading course in Alaska after a few years hiatus from the school.  In this episode: (02:38) Roger talks about the day of the helicopter food drop on a Yukon mountaineering course and how the weather took a drastic turn, leading them to have no food for two days. But since desperate times call for desperate measures, before they completely ran out, the group shared whatever food they had left and ate it together, forming a strong bond between the members and help them survive during the difficult times ahead. (20:40) Roger shares the story about running out of coffee mainly to share the  “real truth.” This may not be a strange scenario in most cases, and everyone runs out of caffeine eventually but what makes it funny is that the rumour wasn't even the real truth. While leading a hiking course, Roger explains that he had his final paperwork flown in with the last food ration. Everything seemed perfect until he realized that he forgot to include every evaluation. Coming closer to the pickup date, Yim had no choice but to compromise his pride to do a call from the sat phone, and instead of stating the ‘real deal' he ended up complaining about the shortage of coffee and requesting them to send a few packs along with the folder he left in the filing cabinet – It's even more hilarious in his narration. (26:11) Roger shares yet another funny story about his companion KG and the giraffe. KG being the most incredible and fantastic instructor, had an entertaining way to educate the students by stating facts about every big animal that walked the forest of Kenya – starting from giraffe all the way to rhinoceros. Not only leaving students hysterical but also the other instructors in the fit of laughter because this class on a NOLS course in Chile! (28:44) Roger takes us back to his experience of Denali Highway and some dog mushers. While his students were on their small group expedition without Instructors on an Alaska Mountaineering NOLS course, he and his pal Andy stumble upon a dog musher company owned by an ex-model. Not able to contain their excitement to meet a model in real life, they paid all their savings for the tour to meet the beauty – but end up disappointed when the model never shows up, and the short-lived tour turns out to be just visiting dogs. (38:35) In the end, Yim shares a story behind “Runaway in Vegas.” He tells us when one of the students was kicked out of the course for breaking the no drug rule, and he was left to take the responsibility to take the student back to the NOLS branch. He further explains how the rebellious kid runs away when hiring a rental car and was nowhere to be found. The story is filled with more thrill and suspense, but as they say, hard work only pays off when it meets the right plan of action – the same goes with this one.

Episode 55 Dark Starts backcountry splitboarding podcast presents Adam Zok ACMG splitboard guide out of Revelstoke BC. While attending Berkeley he joined a ski club where he was able to ride the resorts in Tahoe, Big Sky and Jackson Hole. After guiding at Mt. Shasta in California he wanted to take his guiding career further so he moved to Revelstoke BC and became an ACMG certified guide. Going on his eighth winter in Revelstoke he is now guiding for Selkirk Tangiers Heli Skiing, CAPOW, Revelstoke Backcountry Guides while also planning hut trips and taking private bookings. Adam shares his journey from skateboarding in Santa Barbara California to now being an ACMG certified guide in Revelstoke BC. When he isn’t guiding others through the backcountry he is out exploring and studying ways to ride through new terrain. Adam gave us great pointers on where he went to learn more about the backcountry along with what it takes to take care of yourself and others in emergency situations. So grab a cold one and listen in! Show links: https://www.instagram.com/adamzok/?hl=en https://capow.ca/team/adam-zok/ https://westonbackcountry.com/pages/adam-zok https://snowboardcanada.com/adam-zok-autobiography/ Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

It is Medical Genetics Awareness Week and today we are talking about translocation flagging from PGT-A results. Joining us to discuss this is Dr. Alyssa Snider who is VP of Clinical Genetic Services at Igenomix, and holds both a PhD in genetics and a Master's degree with certification as a genetic counselor. More information on this topic is at www.asrm.org To review this article, https://www.fertstertreports.org ACMG meeting information https://www.acmgmeeting.net Tell us your thoughts on the show by emailing asrm@asrm.org ASRM Today Series Podcasts are supported in part by the ASRM Corporate Member Council.

世界標準であるACMGガイドラインの”カイゼン”を達成！ by bp-Affairs

Episode 51 Dark Starts backcountry splitboarding podcast presents Ty Mills, founder and owner of All Aspects Alpine. Ty was just the second person to ever become a certified ACMG ski guide in Canada on a splitboard. He works for numerous guide services, including Eagle Pass HeliSkiing, 40tribes and Golden Alpine Holidays. He also runs his own guide business All Aspects Alpine, which offers backcountry adventures in Canada and Internationally. Ty loves to play in the mountains. Lazy powder turns, bootpacking up couloirs, laying skin tracks or shredding alpine lines are a few of his favourite things. This guide takes us around the world, sharing his adventures and giving us solid tips from his years as a multi-faceted mountain guide. We learned a lot and hope you will too! Show links: https://aaabackcountryguides.com/ https://www.instagram.com/tymills/ http://www.ogasaka-snowboard.com/index_e.html Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

Episode 49 Dark Starts backcountry splitboarding podcast presents Jon Miller of Backcountry United Foundation. Spending his childhood in areas like Salt Lake City, Utah; San Clemente, California; and Steamboat Springs Colorado Jon was totally immersed in the cultures surrounding art, surfing, skateboarding, snowboarding. Jon has been building connections between the snowmobiling and the snowboarding cultures for 2 decades through branding and storytelling, product innovation and by connecting businesses with their consumers' passions. Jons passion project, Backcountry United Foundation, is a non-profit that aims to create respect between all backcountry users and educate them on how to be safe in the backcountry. Jon shares his stories about how he fell in love with both the human-powered and motorized cultures of the backcountry and now he puts his heart and soul into figuring out how to bridge the gap between them. Listen in and learn more about safely riding in the backcountry and how to keep public lands open for all to enjoy! Show links: https://www.bcufoundation.org/news https://www.powdercowboy.co https://www.instagram.com/powdercowboy/ Episode 51 Dark Starts backcountry splitboarding podcast presents Ty Mills, founder and owner of All Aspects Alpine. Ty was just the second person to ever become a certified ACMG ski guide in Canada on a splitboard. He works for numerous guide services, including Eagle Pass HeliSkiing, 40tribes and Golden Alpine Holidays. He also runs his own guide business All Aspects Alpine, which offers backcountry adventures in Canada and Internationally. Ty loves to play in the mountains. Lazy powder turns, bootpacking up couloirs, laying skin tracks or shredding alpine lines are a few of his favourite things. This guide takes us around the world, sharing his adventures and giving us solid tips from his years as a multi-faceted mountain guide. We learned a lot and hope you will too! Show links: https://aaabackcountryguides.com/ https://www.instagram.com/tymills/ http://www.ogasaka-snowboard.com/index_e.html Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

Episode 48 Dark Starts backcountry splitboarding podcast presents the owner of Stealth Backcountry Tours, Chandler Kane. Chandler started snowboarding in 1989, after seeing Jake Burton and Randy Gateno shred through a tree run he knew he was going to be snowboarding the rest of his life. Founded Stealth Backcountry, offering tours in the Hokkaido mountains of Japan. During the off-season, Chandler chases big storms and powder at Mammoth in California. After life threw Chandler a few curve balls, he found himself booking a trip to go shred in Japan. Returning year after year, he fell in love with the culture and the mountains and decided to start Stealth Backcountry Tours. With years of experience riding in Japan, Chandler gives us amazing tips on gear and what hazards you might run into. So grab a drink and listen in! Show links: https://www.stealthbackcountry.com https://www.instagram.com/stealth_backcountry/?hl=en https://www.facebook.com/StealthBackcountryTours/ https://kingsnowmag.com/you-have-arrived-the-north-face-in-japan/ Episode 51 Dark Starts backcountry splitboarding podcast presents Ty Mills, founder and owner of All Aspects Alpine. Ty was just the second person to ever become a certified ACMG ski guide in Canada on a splitboard. He works for numerous guide services, including Eagle Pass HeliSkiing, 40tribes and Golden Alpine Holidays. He also runs his own guide business All Aspects Alpine, which offers backcountry adventures in Canada and Internationally. Ty loves to play in the mountains. Lazy powder turns, bootpacking up couloirs, laying skin tracks or shredding alpine lines are a few of his favourite things. This guide takes us around the world, sharing his adventures and giving us solid tips from his years as a multi-faceted mountain guide. We learned a lot and hope you will too! Show links: https://aaabackcountryguides.com/ https://www.instagram.com/tymills/ http://www.ogasaka-snowboard.com/index_e.html Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

Episode 47 Dark Starts backcountry splitboarding podcast presents splitboarder Corey Stecker of Smartwool International, General Manager overseeing the Business for both Canada and Europe. Grew up in NYC and discovered snowboarding in ‘88. He crafted his life path to follow his snowboarding passion. Discovered the splitboarding when living in Brek, realizing the bliss of an expansive amount of powder fields now within his reach. Currently lives in Montreal for the perfect blend of city life and proximity to the mountains and manages European & Canadian business for Smartwool. Corey is a fan of everything outdoors! Whether he is mountain biking, trail running, surfing or splitboarding, it all keeps him connected with the mountains. Listen in and spark your own stoke for powder and learn more about gear, sheep and merino wool. Show links: https://www.instagram.com/seestecker/ https://www.instagram.com/smartwool/ Special thanks to: Smartwool https://smartwool.ca/ Use promo code DS10 to get 10% off your purchases worldwide Episode 51 Dark Starts backcountry splitboarding podcast presents Ty Mills, founder and owner of All Aspects Alpine. Ty was just the second person to ever become a certified ACMG ski guide in Canada on a splitboard. He works for numerous guide services, including Eagle Pass HeliSkiing, 40tribes and Golden Alpine Holidays. He also runs his own guide business All Aspects Alpine, which offers backcountry adventures in Canada and Internationally. Ty loves to play in the mountains. Lazy powder turns, bootpacking up couloirs, laying skin tracks or shredding alpine lines are a few of his favourite things. This guide takes us around the world, sharing his adventures and giving us solid tips from his years as a multi-faceted mountain guide. We learned a lot and hope you will too! Show links: https://aaabackcountryguides.com/ https://www.instagram.com/tymills/ http://www.ogasaka-snowboard.com/index_e.html Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

Episode 46 Dark Starts backcountry splitboarding podcast presents Jonathan Penfield, Freeride World Tour Competitor. Through grade school, Jonathan competed with the USSA in half pipe, boardercross and slopestyle competitions. During college he competed in smaller rail jam events, but once he competed in the North Face Masters Tour, he quickly turned his attention to the Freeride World Tour competition. Jonathan has launched an impressive avalanche and weather condition website called livepow.com, all the while still competing. Jonathan is living every snowboarder's dream. His job gives him the freedom to travel around Canada with his girlfriend and chase the pow! And his passion project, livepow.com, provides great information that benefits the entire community. Listen in as he shares how riding in the backcountry prepares him for Freeride competitions, his personal encounters with avalanches and his tips to keep everyone safe in the backcountry. Show links: https://www.instagram.com/jonnpow/ https://livepow.com https://www.instagram.com/livepow_com/ https://www.facebook.com/Jonnp0 https://vimeo.com/155930165 Episode 51 Dark Starts backcountry splitboarding podcast presents Ty Mills, founder and owner of All Aspects Alpine. Ty was just the second person to ever become a certified ACMG ski guide in Canada on a splitboard. He works for numerous guide services, including Eagle Pass HeliSkiing, 40tribes and Golden Alpine Holidays. He also runs his own guide business All Aspects Alpine, which offers backcountry adventures in Canada and Internationally. Ty loves to play in the mountains. Lazy powder turns, bootpacking up couloirs, laying skin tracks or shredding alpine lines are a few of his favourite things. This guide takes us around the world, sharing his adventures and giving us solid tips from his years as a multi-faceted mountain guide. We learned a lot and hope you will too! Show links: https://aaabackcountryguides.com/ https://www.instagram.com/tymills/ http://www.ogasaka-snowboard.com/index_e.html Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

In this instalment of The Avalanche Hour's Third Thursday, I sit down on a Zoom call with an iconic couple out of Prince George, BC. Craig Evanoff and Bonnie Hooge the owner operators of Dezaiko lodge; a beautiful rustic lodge based in the northern Rockies. They have been backcountry adventuring for 30 years and recently Craig released a book with Brett St. Clair called ‘Tips for Beginning Backcountry Skiers'. Craig is an ACMG guide and AST course provider for the northern portion of British Columbia. @dezaikolodge www.Dezaiko.com You tired that old weak saw in your pack? Check out the El Professional snow saw from Primo Snow and Avalanche. They are offering 10% off for The Avalanche Hour Podcast listeners with code: TAH10 when used at checkout. Just head on over to www.primosnowavalanche.com and pick up the saw that cuts straight and is light weight. Don't forget to give them a follow as well @primosnowandavalanche to stay up to date. Also, take a screenshot of your subscription to this podcast to get entered in a draw for one of these saws. The winner will be announced during the Jan 5, 2021 episode with Matt Primono. Follow us on Instagram @theavalanchehour Follow our supporters on Instagram for up to date news from them. @TASBYMND @10barrelbrewing @interwest_insurance Resources on the socials @americanavalancheassociation @avalanchecanada The Avalanche Hour Savings WNDR Alpine skis 10% off: FOWFFR10-4SZB7P Do note that if you order bindings with their skis, there's an automatic 10% ski & binding bundle discount that gets applied and overrides this friends and family one. So, if you are needing to order bindings with your skis, you will have to do so in a separate order unfortunately, otherwise you will only receive 10% off the skis. Good thing is shipping is free, so no additional cost there. HAGAN SKI MOUNTAINEERING 15% off with code: AvalancheHour15 https://alnk.to/6bNgvJb SOCIAL CBD 20% OFF LINK: https://www.avantlink.com/click.php?tt=ml&ti=908357&pw=282549

Episode 36 Dark Starts backcountry splitboarding podcast presents owner of Golden Powder Guides Dave Turner-Crerar. Dave Turner-Crerar immigrated to Canada from Ireland to follow his passion for the outdoors. After a few years of travelling between kayaking the Ottawa River and ski patrolling at Big White Ski Resort, he landed a job with the Edmonton Fire Department. The compressed shift schedule gave him the chance for getting after it in the backcountry. He headed back to school and is now only one small hurdle away from completing the ACMG ski guide program… entirely on a splitboard. Dave also runs his own small guiding outfit, Golden Powder Guiding. Dave got his start as a kayaker, but quickly realized that surfing mountains was his true passion. He started lining up his life to follow his passion. In this episode, we get some amazing tips on boards, boots, skins and wax. We also learn how Dave creates great guided tours, how a guide can help take your AST education to the next level, how Search and Rescue works in Canada, and about insurance? Huge knowledge drops in this episode. Show links: Golden Powder Guiding GPG Instagram Dave Instagram YouTube Channel Sponsored by: The North Face Smartwool Banff Phantom Splitboard Bindings Qwax wax Other: Lifestyle Financial Insurance Special thanks to: Tahoe Lab Boards Use promo code DS15 to get 15% off all boards Groundswell Marketing Valerie Black The Artist Behind The Logo Follow us on Instagram: @ Darkstarts.podcast @ Darkstarts.media

Episode 34 Dark Starts backcountry splitboarding podcast presents the first female to examine on a splitboard to a guide Christine Feleki. Growing up in Canmore, AB, Christine learned to be faster by riding with both skiers and boarders, eventually discovering the backcountry She’s the first female splitboard guide to pass the ACMG exam, putting down fresh tracks for other women who are brave enough to follow Her growing list of sponsors includes Pallas, Arc’teryx, and Phantom - all stemming from her chance meeting with Steph Nitsch through She Jumps Working as a guide, she has dialed in her gear - and runs down her tried and tested picks… we’re almost convinced to try hard booting now Christine’s happy place is the backcountry. She answered the call of the mountains, and now spends her days touring and guiding, making memories for the guests that she brings into the backcountry. When you spend that much time in the backcountry, you develop deep knowledge of gear and hone your own art of skinning as a guide. This one’s gold, Jerry! Gold! Show links: Instagram Pallas Snowboards Arc’teryx Phantom She Jumps Special thanks to: Tahoe Lab Boards Use promo code DS15 to get 15% off all boards Groundswell Marketing Valerie Black The Artist Behind The Logo Follow us on Instagram: @ Darkstarts.podcast @ Darkstarts.media

Welcome to the first Third Thursday with Wes Gregg. In this episode I talk with Kyle Lamothe who is a park rat from the icy slopes of northern Ontario, Canada turned Ski Mountaineer. He packed up and relocated to the Canadian rockies before finally settling into a little ski town called Revelstoke, British Columbia. After gaining an education and establishing a career in hospitality, Kyle took a single trip to Sol Mountain Lodge. Upon his return he ditched the suit and tie, and embarked on his path as a ski guide. Due to the current global pandemic, Kyle's progress was significantly impacted. He finds himself now in limbo in the hopes of being able complete his ACMG guide exam this winter. Kyle spends 100+ days a season ski touring recreationally, as well as Tail guiding at Sol Mountain Lodge. Also this episode we introduce the El Professional snow saw from Primo Snow and Avalanche by offering a 10% off discount code: TAH10 when used at checkout. Just head on over to www.primosnowavalanche.com and pick up the saw that cuts straight and is light weight. Don't forget to give them a follow as well @primosnowandavalanche Also, take a screenshot of your subscription to this podcast to get entered in a draw for one of these saws. The winner will be announced during the Jan 5, 2021 episode with Matt Primono. Follow us on Instagram @theavalanchehour Follow our supporters on Instagram for up to date news from them. @TASBYMND @10barrelbrewing @interwest_insurance Resources on the socials @americanavalancheassociation @avalanchecanada

Episode 25 Dark Starts backcountry splitboarding podcast presents pro rider, AMCG guide and owner of Spline Snowboards Justin Lamoureux: His early days as a pro boarder led him to become a World Champion, compete in the 2006 and 2010 olympics, and 3x canadian national halfpipe champion His experience working at K2 and background as a mechanical engineer inspired the founding of Spline Snowboards, creating unreal boards As a certified Accredited Canadian Mountain Guide, he shares awesome tips on gear, safety, terrain and what to pack on your next tour Justin knew he loved snow at an early age. And he loved it hard. He even reworked his college schedule and put every penny he had into chasing it. It brought him fame, glory, and a great career. His engineering background led his curious mind to start building his own boards, and his ability to push the edge created the most unique boards we’ve ever seen. He’s also inspiring his young son to follow in his skin tracks. We’re inspired too! Show links: Spline Snowboards Spline Instagram Justin Instagram Time Bomb Trading Rudeboys Shop Clif Bar Thirty Two Boots Spark R and D Arc'teryx Justin Lamoureux.com Special thanks to: Tahoe Lab Boards Use promo code DS15 to get 15% off all boards Groundswell Marketing Valerie Black The Artist Behind The Logo Follow us on Instagram: @ Darkstarts.podcast @ Darkstarts.media

Episode 24 Dark Starts backcountry splitboarding podcast presents avalanche expert and mountain guide John Buffery. Guide, educator, film consultant, speaker, writer, avalanche expert, mountain guru Pioneer splitboarder, advocated the adoption of snowboarding into guiding for the growing number of snowboards in backcountry Spent years as a personal guide for the godfather of freeriding, Craig Kelly His avalanche experience and education catapulted his career in film consulting, the founding of Baldface Lodge and keeping roads safe in BC. His roots run as deep as his chakras. We loved talking to Buff about his amazing stories and over three decades of experience in backcountry and avalanche safety. An avalanche in a helicopter, playing chess with Craig Kelly, the origins of Baldface Lodge - this episode has got it all! We still don’t know if he really invented the first splitboard. Listen in and let us know what you think. Show links: Safety Wrangler Website John Buffery Instagram IMDB Credits @depthperceptionfilm @baldfacelodge Special thanks to: Tahoe Lab Boards Use promo code DS15 to get 15% off all boards Groundswell Marketing Valerie Black The Artist Behind The Logo Follow us on Instagram: @ Darkstarts.podcast @ Darkstarts.media

Episode 21 Dark Starts backcountry splitboarding podcast presents adventurer and ACMG guide in training Seb Grondin. Quebec born now calls Revelstoke home, with annual poutine pilgrimage Most recent adventure? Paddled 140 km down the Columbia river from Mica to Revelstoke winter camping and splitting along the way Accepted into AMCG program and completing courses while guiding for K3 Cat Ski and working summers rock scaling mountains Man, we love Quebecers - they’re the good kind of nuts. It takes a special kind of person to paddle down a river in the middle of January in search of fluffy pillows and undiscovered lines. That’s a film we’re all gonna want to see! Find out what made Seb fall in love with Revelstoke 13 years ago and check out his many adventures since then. Grab yourself a Labatt's 50, get comfy, and enjoy this awesome episode! Show links: Seb Grondin Nitro Squash Split Board Butter Wax Without a Paddle Film Revelstoke Society Hotel Village Idiot Grub Wast3d Youth Society Snow & Split K3 Cat Ski GoPro Grill Mount @almondmfg Special thanks to: Tahoe Lab Boards Use promo code DS15 to get 15% off all boards Groundswell Marketing Valerie Black The Artist Behind The Logo Follow us on Instagram: @ Darkstarts.podcast @ Darkstarts.media

Episode 14 Dark Starts backcountry splitboarding podcast presents ACMG guide Joey Vosburgh. One of the first Association of Canadian Mountain Guides ski guides on a snowboard Often chirped for his hard boots, but his transitions are impressive Amazing tips on terrain and surviving a slide Joey takes us behind the scenes of mountain guide reporting and reading terrain. His deep knowledge, engaging stories and unique perspective on gear come from his decades of experience of splitboarding and riding in the backcountry. Listen to his amazing tips that could be the missing piece of the puzzle that you needed to hear. Show links: Instagram Arcteryx ACMG Capow Selkirk Tangiers Heli Selkirk Mountain Experience Phantom Bindings Jones Snowboards Smartwool socks Special thanks to: Tahoe Lab Boards Use promo code DS15 to get 15% off all boards Groundswell Marketing Valerie Black The Artist Behind The Logo Follow us on Instagram: @ Darkstarts.podcast @ Darkstarts.media

Picture Genetics Kit Giveaway! Enter to win your own free kit on our Twitter, Instagram, and Facebook.Guests for this episode are from Fulgent Genetics (offering Picture Genetic kits), which is the sponsor of this new Direct To Consumer Genetic Testing Series. Jessica Shiles is a genetic counselor and Dr. Samuel Strom is the lab director.Jessica serves as Fulgent’s Clinical Genetics Marketing Specialist. Her main role is to provide clinical training and expertise to help develop marketing material that is used to educate, support, and inform the patients and providers Fulgent serves. With Jessica’s strong passion for patient advocacy, she also leads Fulgent’s community outreach. She is a fellow Sarah Lawrence College’s alumni where she received her Masters of Science in Human Genetics.Previously Dr. Strom was an assistant professor at the UCLA David Geffen School of Medicine where he pioneered interpreting genomics results in the context of clinical diagnostic testing for rare inherited diseases and cancer. At Fulgent, he is continuing to forward this new science at an industrial scale. He is also an accomplished researcher in the fields of neurogenetics, ophthalmic genetics, and molecular diagnostics, with publications in top journals such as Science, JAMA, Genetics in Medicine, and Human Molecular Genetics.On This Episode We Discuss:Overview of Picture Genetics’ approach to DTCs (including genetic counseling)Difference between DTC genotyping and sequencingConditions on carrier screening (Picture Parenting)Ideal time for carrier screeningNewborn testing for healthy vs sick babiesNewborn testing vs newborn screeningConditions on newborn testing (Picture Newborn)Value of newborn testing after negative carrier screeningACMG59 qualification of conditions (Picture Wellness)Purpose of ordering testing on the ACMG59 genesCOVID-19 DTC testing, including FDA approvalThere is one correction during the episode, Jessica mentioned ACMG when she meant to say ACOG.As a DNA Today listener you can order your kits with code “DNATODAY” for a 25% discount and free shipping. Order at picturegenetics.com and the kit will be delivered right to your home! Thanks for Picture Genetics for sponsoring this DTC series. Don’t forget to enter our Picture Genetics Kit Giveaway on our Twitter, Instagram, and Facebook.Stay tuned for the next new episode of DNA Today on September 4th, 2020! New episodes are released on the first Friday of the month with some bonus episodes thrown in there. In the meantime, you can listen to over 125 other episodes on Apple Podcasts, Spotify, or streaming on the website. Questions/inquiries can be sent to info@DNApodcast.com.

Episode 12 Dark Starts backcountry splitboarding podcast presents splitboard gypsy, avalanche instructor, and guide in training Michael Wigley. - If you want to become a ski mountaineer, this is what you gotta do - Broken bones are just a minor setback, determination is the key to success - Right place, right time, Mountain Mike knows how to trust his gut to find the perfect pow and stay safe - Plant based living, cooking and fantastic gear roundup Michael Wigley is on track to becoming a splitboard guide pursuing his ACMG certification. He’s cut his teeth in this world by living like a gypsy in the mountains. Spanning over 20 years, over 5 continents, and up and down many, many mountain ranges. You’re going to learn a lot from his amazing stories, packing tips, gear and survival skills. Show links: Instagram Venture Snow Venture Snowboards Keefer Lake Lodge Baldface Lodge Spark R&D Spark Bindings Special thanks to: Visit our website for great deals from our sponsors: www.darkstarts.ca/partners Groundswell Marketing www.instagram.com/groundswell_fm/ Valerie Black The Artist Behind The Logo www.instagram.com/valerieblack.art/ Follow us: www.darkstarts.ca @ Darkstarts.podcast https://www.instagram.com/darkstarts.podcast/ @ Darkstarts.media https://www.instagram.com/darkstarts.media/

Genetic and genomic information is a powerful tool in personalized medical care. It is essential for both diagnostic purposes and medical management. But when it comes to genetic test results, electronic health records (EHRs) are generally not searchable or standardized. Tune in to this month’s GenePod, Genetics in Medicine’s monthly podcast, to hear co-authors Dr. Theresa Grebe, a clinical geneticist at Phoenix Children’s Hospital, and Dr. Marc Williams, director emeritus of the Genomic Medicine Institute at Geisinger, discuss ACMG’s recent points to consider statement from the ACMG on the interface of genomic information with the EHR and how to optimize EHRs for genomic medicine. See acast.com/privacy for privacy and opt-out information.

In this episode of ASRM Today, we are speaking with genetic counselor Aishwarya Arjunan about the updated American College of Medical Genetics and Genomics (ACMG) guidelines concerning cystic fibrosis screening. Ms. Arjunan is currently the Clinical Product Specialist for Carrier Screening at Myriad Women's Health in San Francisco, California.  Deignan, J.L., Astbury, C., Cutting, G.R. et al. CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med (2020). https://doi.org/10.1038/s41436-020-0822-5 You can learn more about the updated guidelines of the American College of Medical Genetics and Genomics at their website: https://www.acmg.net/

Leah Evans grew up in Rossland, British Columbia skiing at RED Mountain Resort but she calls Revelstoke her home today. She has competed in freeride and big mountain competitions and has been featured in video projects like the satirical film “Dream Job”. Most notably, Leah is the founder of Girls Do Ski, which hosts multi-level freeski camps and facilitates mentorships for women looking to grow on and off the mountain. Tune in to hear Leah talk about women working together as enablers rather than competitors, music in nature, what connecting youth to wild spaces can look like and why passing her ACMG guide exam was so empowering. Big thanks to our sponsors Protect Our Winters, OpenSnow, SKI Magazine, the IKON Pass. Learn more about your ad choices. Visit megaphone.fm/adchoices

Is more better? As the cost of genetic testing plummets, allowing more people to get testing of more genes, researchers and clinicians are asking: who should get tested, and for what? One recent study suggested that all breast cancer patients should get genetic testing. But does the evidence support this approach? In a recent ACMG statement published in Genetics in Medicine (GIM), the statement’s authors weighed the evidence for BRCA1/2 and other germline genetic testing in patients with breast cancer and recommended points for clinicians to consider. On this month’s episode of GenePod, GIM’s monthly podcast, host Cynthia Graber talks with Dr. Tuya Pal, associate director for cancer health disparities at the Vanderbilt University Ingram Cancer Center and first author of ACMG’s recent statement, and Dr. Susan Domchek, director of the Basser Center for BRCA at the University of Pennsylvania and author of a commentary on the ACMG statement, about the evidence, gaps in current knowledge, and how to improve testing rates among high-risk patients. See acast.com/privacy for privacy and opt-out information.

“It’s been a crazy time,” says Gillian Hooker, of the first 5 weeks of her year as President of the National Society of Genetic Counselors. NSGC is attempting to rally support around HR3235, a long-discussed and long-promised federal bill that would permit CMS to recognize genetic counselors as medical caregivers for the purposes of billing, that FINALLY made it to Congress in 2019. A possible wrench in the gears? ACMG announced last month that it cannot support the bill as written. Why not? Will it matter?

23andMe lays off over 100 employees. Illumina comes to the JP Morgan empty-handed. Has Precision Medicine seen it’s heyday already? Or are we gearing up for another wave of innovation? Nathan and Laura are again ready for the tough questions of genomics. We begin with the current spat between genetic counselors and the ACMG. Like, . . . huh?

On January 9, the American College of Medical Genetics sent a letter to members of the House of Representatives, voicing their opposition to HR 3235, a bill that would allow genetic counselors to be reimbursed by CMS for providing genetic counseling. The ACMG recommended additional language related to the scope of practice of genetic counselors, most notably opposing the ordering of genetic tests by genetic counselors.Ellen Matloff, a certified genetic counselor and the founder and CEO of My Gene Counsel, discusses the historical and social context for this opposition and explains why she sees this as part of a broader #MeToo moment in genetic counseling. Related Links and Resources ACMG Letter to Congress Grey Genetics blog post article on Medicare and HR 3235: “Does Medicare Cover Genetic Counseling?” H.R.3235 - Access to Genetic Counselor Services Act of 2019 Erica Ramos’ (Past NSGC President) twitter thread on GCs and test ordering Stoll, Katie. “Is There A Doctor in the House? Physician-Mediated DTC Genetic Testing.” The DNA Exchange. January 6, 2020. Adverse Events in Genetics Testing: A Case Series Adverse Events in Cancer Genetic Testing: the third case series Adverse Events in Genetic Testing: The Fourth Case Series My Gene Counsel NSGC Resources to Advocate for H.R.3235 Are you looking for genetic counseling? Grey Genetics is an independent telehealth genetic counseling and consulting company. Book an appointment with a genetic counselor specialized in your area of concern. All genetic counseling appointments take place over secure, HIPAA-compliant video-conferencing or by phone. Grey Genetics on Twitter: @GreyGenetics Grey Genetics on Instagram: @greygenetics Grey Genetics on Facebook Grey Genetics on LinkedIn

Our special edition podcast for UN International Mountain Day 2019 (December 11th) brings you a panel of experts discussing the impacts of climate change on mountain ecosystems and communities. Canadian Mountain Network trainee and Mount Royal University journalism student Blaise Kemna recorded this engaging event held on November 4, 2019 at the Glenbow Museum in Calgary, AB. The discussion features the perspectives of mountain researchers and guides who have contributed to The Alpine Club of Canada's annual State of the Mountains Report: Will Gadd - Named Mountain Hero by UN Environment; ACMG mountain guide; renowned mountain athlete Jim Gudjonson - Director of the Sustainability Office, Thompson Rivers University; ACMG/IFMGA mountain guide; and Vice-President for Facilities, Alpine Club of Canada David Hik - Professor of Biological Sciences, Simon Fraser University Lael Parrott - Professor of Earth, Environmental, Geographic Sciences and Biology, UBC Okanagan; Vice-President for Access & Environment, Alpine Club of Canada Dan Shugar - Associate Professor of Geosciences; and Director, Environmental Science Program, University of Calgary

On this episode, we explore the pediatric speciality of genetic counseling. Guest Sam Toy is a pediatric genetic counselor at the Washington University School of Medicine in St. Louis. She earned her BS in Biology and MS in Professional Biology from Indiana University. She went on to earn her MS in genetic counseling from Indiana State University.On This Episode We Discuss:The role of a pediatric genetic counselorOutline of a genetic counseling sessionUnique aspects of pediatric genetic counselingGenetic testing whole genome/exome vs specific genesGenetic testing results’ give a diagnosis, change medical management, and insurance coveragePsychosocial aspects of counselingTransitioning from grad school to being a genetic counselor full timeApplication deadlines are approaching for genetic counseling grad schools, if you are working on your applications check out episode 87 which features tips from genetic counseling students on applications. Then episode 97 has advice on the other half of the application process (interviews, ranks, and match) once January/February rolls around.Next week is Thanksgiving in the US, and that means it’s National Family Health History Day, so if you have an opportunity with family this holiday ask them about health history, it’s the best genetic test we have!Variant classification and interpretation have become important skills for genetic counselors. But it takes so long! Even if it’s just a VUS you want to double check. To make it streamlined check out franklin.genoox.com/DNAToday. You can access so much information about a variant including relevant publications, automated ACMG classifications, annotations and phenotypes/disease. Best part? It’s free! All this data about one variant is compiled at your fingertips. No more sifting through PubMed! Join the future of variant interpretation.Stay tuned for the next new episode of DNA Today on December 6th, 2019. New episodes are released on the first Friday of the month with some bonus episode thrown in there. See what else I am up to on Twitter, Instagram, Facebook and iTunes. Questions/inquiries can be sent to info@DNApodcast.com.

MTHFR... Yep, it gets blamed for a variety of health and pregnancy concerns. But does the data actually confirm the presence of adverse pregnancy and adverse health issues with MTHFR variants? In this session, we will review the difference between the 2 most common variants (C677T, A1298C) and true MUTATIONS. We will also review statements from the ACOG, ACMG, SMFM, as well as the Canadian Guidelines regarding MTHFR screening.

Jane Ferguson:  Hi, everyone. Welcome to Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. It's May 2019, and this is episode 28. So let's see what papers we have in the journal this month.                              First up, a paper from Mengyao Yu, Nabila Bouatia-Naji and colleagues from the Inserm Cardiovascular Research Center in Paris, entitled GWAS-Driven Gene-set Analyses, Genetic and Functional Follow-Up Suggest Glis1 as a Susceptibility Gene for Mitral Valve Prolapse.                              In this paper, they set out to characterize the genetic contributions to mitral valve prolapse, or MVP, to better understand the biological mechanisms underlying disease. They applied the gene-set enrichment analysis for QWAS tool and the pathway enrichment tool DEPICT to existing GWAS for MVP in a French sample to identify gene sets associated with MVP. They find significant enrichment of genes involved in pathways of relevance to valve biology and enrichment for gene expression in tissues of relevance to cardiovascular disease.                              They zeroed in a Glis family zinc finger gene Glis1 with consistently strong pattern of evidence across the GWAS enrichment and transcription analyses. They replicated the association between Glis1 and MVP in a UK biobank sample. They found that Glis1 is expressed in valvular cells during embryonic development in mice, but is mostly absent at later times. They targeted two Glis1 orthologs in zebrafish and found that knockdown of Glis1 B was associated with a significant increase in the incidence of severe atrioventricular regurgitation. These data highlight Glis1 as a potential regulator of cardiac valve development with relevance for risk of mitral valve prolapse.                              Next up is a paper from Gina Peloso, Akihiro Namuro, Sek Kathiresan and colleagues from Boston University, Kanazawa University, and Mass General Hospital. In their paper, Rare Protein Truncating Variance in APOB, Lower LDL-C, and Protection Against Coronary Heart Disease, the team was interested in understanding whether protein truncating variance in APOB underlying familial hypobetalipoproteinemia confer any protection against coronary heart disease.                              They sequenced the APOB gene in 29 Japanese families with hypobetalipoproteinemia as well as in over 57,000 individuals, some with early onset CHD and some without CHD. They found that presence of an APOB truncating variant was associated with lower LDL cholesterol and lower triglycerides, and also with significantly lower risk for coronary heart disease. This study confirms that variance in APOB, leading to reduced LDL and triglycerides are also protective against coronary heart disease. :                            The next paper entitled Mortality Risk Associated with Truncating Founder Mutations in Titin comes to us from Mark Jansen, Dennis Dooijes, and colleagues from University Medical Center Utrecht. They analyzed the effect of titin truncating variance on mortality in Dutch families. Titin truncating variants are associated with dilated cardiomyopathy, but have a very variable penetrance.                              In this study, the authors looked at three titin truncating variants, established to be founder mutations, and traced the pedigrees back to 18th century ancestors. They looked at 61 individuals on the transmission line and 360 of their first-degree relatives. They find no evidence for excess mortality in variant carriers overall. However, when they restrict it to individuals over 60 years of age, they did find a significant difference in mortality, which was also observed in individuals born after 1965. What these data tell us is that these titin truncating variants have a relatively mild phenotype with effects on mortality only manifesting later in life in many carriers. Given increases in life expectancy over the past several decades, the prevalence of morbidity and mortality attributable to titin truncating variants may increase. Genetic screening may identify genotype-positive, phenotype-negative individuals who would benefit from preventative interventions.                              Continuing on the theme of genetic variance, we have a paper from John Giudicessi, Michael Ackerman, and colleagues from the Mayo Clinic, Assessment and Validation of a Phenotype-Enhanced Variant Classification Framework to Promote or Demote RYR2 Missense Variants of Uncertain Significance. In this paper, they aim to find a better way to classify variants of unknown significance, of VUS, in the RYR2 gene. Variants in this gene are commonly associated with catecholaminergic polymorphic ventricular tachycardia, or CPVT.                              They examined 72 distinct variants in 84 Mayo Clinic cases and find that 48% were classified as VUS under ACMG guidelines. The rate was similar in a second sample from the Netherlands, with 42% of variants originally classified as VUS. They developed a diagnostic scorecard to incorporate a pretest clinical probability of CPVT, which included various clinical criteria, including symptoms and stress test results. Application of the phenotype enhanced ACMG criteria brought the VUS rate down to 7% in Mayo Clinic and 9% in the Dutch samples. The majority of VUS were reclassified as likely pathogenic.                              This study highlights how incorporation of disease-specific phenotype information can help to improve variant classification and reduce the ambiguity of reporting variants of unknown significance.                              We also have a number of research letters in the journal this month. From Karine Ngoyen, Gilbert Habib, and coauthors from Marseilles, we have a paper entitled Whole Exome Sequencing Reveals a Large Genetic Heterogeneity and Revisits the Causes of Hypertrophic Cardiomyopathy, Experience of a Multicentric study of 200 French Patients. In this study, they examined the genetic contributions to hypertrophic cardiomyopathy, or HCM, in 200 individuals as part of the HYPERGEN study and compared the benefits of whole exome sequencing compared with targeted sequencing of candidates' sarcomeric genes. All subjects had HCM documented by echocardiography.                              In the whole exome sequencing data, they first looked for mutations within 167 genes known to be involved in cardiomyopathies or other hereditary diseases. Of these 167 virtual panel genes, they find variants in 101 genes. Following whole exome sequencing, over 87% of the patients had an identified pathogenic, or likely pathogenic, mutation compared with only 35% of patients who only had targeted sequencing of sarcomeric genes.                              This highlights the generic heterogeneity of HCM and suggests that whole exome sequencing has utility in identifying variants not covered by sarcomeric gene panels.                              The next letter is from Wouter Te Rijdt, Martin [Vandenberg] and colleagues from University Medical Center Groningen and states that [dissynchronopathy] can be a manifestation of heritable cardiomyopathy. They hypothesized that left bundle branch block, also designated as dissynchronopathy, may be a manifestation of familial cardiomyopathy.                              They analyzed patients from a database of cardiac resynchronization therapy and identified super-responders whose left ventricular dysfunction was normalized by therapy. They carried out targeted sequencing in 60 known cardiomyopathy genes in 16 of these super-responder individuals and identified several variants, including a pathogenic variant in troponin T in one individual and variants of unknown significance in nine individuals. Pedigree analysis identified multiple family members with dilated cardiomyopathy.                              This study highlights that dissynchronopathy can be a manifestation of DCM, but that affected individuals may still benefit from cardiac resynchronization therapy.                              The next letter entitled Targeted Long-Read RNA Sequencing Demonstrates Transcriptional Diversity Driven by Splice-Site Variation in MYBPC3 comes from Alexandra Dainis, Euan Ashley, and colleagues from Stanford University. They set out to understand whether transcriptome sequencing could improve the diagnostic yield over genome sequencing in patients with hypertrophic cardiomyopathy. In particular, they hypothesized that long-read sequencing would allow for identification of alternative splicing linked to disease variance. They used long-read RNA and DNA sequencing to target the MYBPC3 gene in an individual with severe HCM who carried a putative splice-site altering variant in the gene. They were able to obtain heart tissue for sequencing and included several HCM and control subjects in addition to the patient with the MYBPC3 variant.                              They identified several novel isoforms that were only present in the patient sample, as well as some additional isoforms, including retained introns, extended exons, and an additional cryptic exon, which would not have been predicted based on the DNA variant. While the effects on protein function is not known, the transcripts are predicted to be translated.                              This analysis highlights the effect of a rare variant on transcription of MYBPC3 and provides additional evidence to link the variant to disease. This is a really nice approach, which could be used to probe causality and mechanisms, not only for cardiovascular disease, but for other rare variants in many disease settings.                              We finish with a perspective piece from Nosheen Reza, Anjali Owens, and coauthors from the University of Pennsylvania entitled Good Intentions Gone Bad, The Dangers of Sponsored Personalized Genomics. They present a case of a 23-year-old woman who presented for genetic counseling and evaluation after discovering she carried a likely pathogenic MYH7 variant associated with cardiomyopathy. She had no significant medical history, but had participated in employer-sponsored genetic testing motivated to identify potential variants related to cancer given a family history of cancer.                              After receiving her results, she experienced considerable anxiety and stopped exercising out of fear of cardiac complications. She visited an ER after experiencing chest pain, something she had not experienced previously. There was no appropriate counseling available at her institution for her genetic test results, leading her to seek out the additional counseling. Thus, while she was initially motivated to complete genetic testing because her employer offered it free of change, she ended up incurring costs related to the followup evaluation and counseling. Ultimately, she had no significant clinical findings. Although the variant had been listed as likely pathogenic, other sources consider it to be of unknown significance.                              This story highlights the psychological and financial impact that genetic testing can have on individuals, particularly when carried out without any pretest counseling or accessible post-test support when variants are identified.                              Despite the considerable promise of personalized medicine, there are many complexities to be considered, particularly with direct-to-consumer testing and employer-sponsored testing. This perspective highlights the ethical considerations and urges caution to maintain the best interests of patients.                              That's all for this month. Thanks for listening. I look forward to bringing you more next month.                              This podcast was brought to you by Circulation Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2019.  

This Memorial Day weekend we have a double action-packed review of DC'S DOOM PATROL and JOHN WICK 3.We also talk about what's new in the world of ACMG including a recent episode of CLOAK & DAGGER that officially connects to the MCU and much more. All here on this edition of A.C.M.G. presents TALK TIME LIVE!

In this special episode, join the Rare in Common team on the floor at the American College of Medical Genetics and Genomics (ACMG) annual meeting in Seattle. As the team walked around the conference, Andra had the opportunity to chat with members of the genetics community in attendance, from geneticists to genetic counselors to advocates. After speaking with the guests, it’s clear there is a positive outlook for the rare community with the help of advancements in genetics.

THE FINAL ROAD to the 11 YEARS of MARVEL MOVIES IS HERE!!! This week we FINALLY get to review AVENGERS ENDGAME!Host Daxavier Josiah and special guest Joe Rinaldi run down the movie to see if it did pay off as well as what performances stood out the most, favorite scenes, and where this will possibly lead to next.All this and much more in this edition of ACMG presents TALK TIME LIVE.

This episode is the first in a special series recorded live at the 2019 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting in Seattle. We had the honor of speaking with Dr. Anthony Gregg, the incoming president of ACMG, to get his perspective on what medical genetics brings to the practice of medicine. Dr. Gregg shares the benefits of getting rare genetic disorders diagnosed early, and the many ways in which this knowledge can help families plan and prepare. Dr. Gregg also provides a fun and interesting lesson in genetics that everyone can understand.

Jane Ferguson:                Hello, and welcome to episode 26 of Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson. It's March 2019, and I'm ready to spring into this month's papers, and apparently make really bad seasonal related jokes. Sorry all. Okay, let's get started.                                            First up, is a paper from Oren Akerborg, Rapolas Spalinskas, Sailendra Pradhananga, Pelin Sahlén and colleagues from the Royal Institute of Technology in Solna, Sweden entitled "High Resolution Regulatory Maps Connect Vascular Risk Variants to Disease Related Pathways." Their goal was to identify non-coding variants associated with coronary artery disease, particularly those with putative enhancers and to map these to changes in gene function. They generated genomic interaction maps using Hi-C chromosome confirmation capture, coupled with sequence capture in several cell types, including aortic and ethelial cells, smooth muscle cells and LPS stimulated THP-1 macrophages.                                            They captured over 25,000 features and they additionally sequenced the cellular transcriptomes and looked at epigenetic signatures using chromatin immunoprecipitation. They looked at regions interacting with gene promoters and found significant enrichment for enhancer elements. Looking at variants previously implicated in genome-wide associated studies, they identified 727 variants with promoter interactions and they were able to assign potential target genes for 398 GWAS variants.                                            In many cases, the gene associated with a particular variant was not the closest neighbor, highlighting the importance of considering chromatin lupane when assigning intergenic variants to a gene. They identified several variants that interacted with multiple promoters, influencing expression of several genes simultaneously.                                            Overall, this paper is a great resource for the community and takes many of these GWAS hits to the next level in starting to understand their biological relevance. They have a lot of supplemental material available online so it's definitely worth checking that out and taking a look for your favorite non-coding variant or chromosomal region to see if you can get some more information on it.                                            Next up, Pierrick Henneton, Michael Frank and colleagues from the Hopital Europeen Georges-Pompidou in Paris bring us "Accuracy of Clinical Diagnostic Criteria For Patients with Vascular Ehlers-Danlos Syndrome in a Tertiary Referral Center." The authors were interested in determining the accuracy of the diagnostic criteria used to select patients for genetic testing for suspected vascular Ehlers-Danlos syndrome. This is because, despite the Villefrench criteria being recommended for diagnosis, the accuracy of the diagnostic criteria was never formally tested.                                            They selected 519 subjects, including 384 probands and 135 relatives who had been seen between 2001 and 2016. They assessed the sensitivity and specificity of the Villefrench classification. Almost 32% of tested individuals carried a pathogenic COL3A1 variant. The sensitivity of the Villefrench criteria was 79% with a negative predictor value of 87%. Symptomatic probands had the highest accuracy at 92% sensitivity and 95% negative predictive value. However, the specificity was just 60%.                                            Applying revised diagnostic criteria from 2017, it was actually less accurate because even though there was an increase in specificity, the sensitivity was reduced. Overall diagnostic performance was worst in individuals under 25 and neither set of diagnostic classifications allowed for early clinical diagnosis in individuals without a family history.                                            Our next paper is a Mendelian randomization analysis from Susanna Larsson, Stephen Burgess and colleagues from Uppsala University and the University of Cambridge. This paper entitled "Thyroid Function And Dysfunction In Relation to Sixteen Cardiovascular Diseases: A Mendelian Randomization Study" aims to understand how subclinical thyroid dysfunction relates to risk of cardiovascular diseases. They generated genetic predictors for thyroid stimulating hormone, or TSH, through a GWAS meta-analysis in over 72,000 individuals. They then analyzed the association of genetically predicted TSH with cardiovascular outcomes in large GWAS studies of atrial fibrillation, coronary artery disease, and ischemic stroke, and further assessed associations with phenotypes in the UK Biobank.                                            They found genetically decreased TSH levels and hyperthyroidism were associated with increased risk of atrial fibrillation but not other tested phenotypes. Overall, these data support a causal role for TSH and thyroid dysfunction in atrial fibrillation but not in other cardiovascular diseases.                                            The next paper is also a Mendelian randomization analysis from members of the same group, Susanna Larsson, Stephen Burgess and colleagues published "Resting Heart Rate and Cardiovascular Diseases: A Mendelian Randomization Analysis." In this letter, they describe a study of the relationship between genetically increased resting heart rate and cardiovascular diseases. They constructed genetic predictors of resting heart rate and similarly to the previous study, used that as an instrument to test for associations with coronary artery disease, atrial fibrillation, and ischemic stroke in the cardiogram, atrial fibrillation, and mega stroke consortia respectively.                                            They also looked at 13 CVD outcomes in the UK Biobank. They found that genetically predicted heart rate was inversely associated with atrial fibrillation with suggestive evidence for an inverse association with ischemic, cardioembolic, and large artery stroke. The inverse association with AF was replicated in the UK Biobank, supporting previous reports linking resting heart rate to atrial fibrillation.                                            Next up, we have a letter from Robyn Hylind, Dominic Abrams, and colleagues from Boston Children's Hospital. This study entitled "Phenotypic Characterization of Individuals with Variants in Cardiovascular Genes in the Absence of a Primary Cardiovascular Indication For Testing" describes their work to probe incidental findings for potential cardiovascular disease variants in individuals undergoing clinical genomic sequencing for non-cardiac indications.                                            They included 33 individuals who had been referred as carrying variants that were indicated as being associated with cardiovascular disease in primary or secondary findings. The variants were reclassified using the 2015 ACMG guidelines, and then were compared to the original classification report obtained at the time of sequencing.                                            Of 10 pathogenic or likely pathogenic variants, only four of these were actually considered pathogenic or likely pathogenic after reclassification under the 2015 ACMG criteria, and none of these were associated with a cardiac phenotype. None of the variants could be definitively linked to any cardiac phenotype.                                            The costs ranged from $75 to over $3700 per subject with a cost per clinical cardiac finding estimated at almost $14,000. This study highlights the relatively high cost and low yield of investigating potential cardiovascular variants and prompts consideration of how to implement strategies to ensure that variant reporting maximizes clinical return but minimizes the financial, time, and psychological burdens inherent in lengthy follow-ups.                                            The next paper is a clinical letter from Serwet Demirdas, Gerben Schaaf and colleagues from Erasmus University Rotterdam  entitled "Delayed Diagnosis of Danon Disease in Patients Presenting with Isolated Cardiomyopathy." They report on a clinical case of a 14-year-old boy presenting with cardiac arrest due to ventricular fibrillation during exercise. Echocardiography and MRI showed cardiac concentric hypertrophy, particularly in the left ventricle. The boy's mother had died at age 31 after being diagnosed with peripartum dilated cardiomyopathy.                                            Sequencing in the boy revealed a variant in the LAMP2 gene, known to be responsible for Danon disease, which typically presents as cardiomyopathy, skeletal myopathy, and intellectual disability. This same LAMP2 variant was found in preserved maternal tissue, but not in other family members. In this case, there was no evidence of muscle or intellectual abnormalities. However, sequencing had allowed for this diagnosis of Danon disease in the child and posthumously in his mother. This study demonstrates a utility of using extended gene panels in clinical sequencing to aid in diagnosis and to inform management of patients.                                            The next letter is from Alvaro Roldan, Julian Palomino-Doza, Fernando Arribas and colleagues from University Hospital of the 12th of October in Madrid and is entitled "Missense Mutations in the FLNC Causing Familial Restrictive Cardiomyopathy: Growing Evidence." This report also highlights clinical cases. In this case, two individuals with variants in the filamin C, or FLNC gene. Two unrelated individuals presenting with restricting cardiomyopathy were sequenced and found to carry two different variants in the FLNC gene, one of which had not been previously reported.                                            This expands the number of reported cases of filamin C mutations in restrictive cardiomyopathy and highlights the need for further study of the pathophysiology linking filamin C to cardiac function.                                            Finally, we have some correspondence related to a previously published article. In the letter, Christopher Chung, Briana Davies, and Andrew Krahn comment on the recently published article from Jody Ingles on concealed arrhythmogenic right ventricular cardiomyopathy in sudden unexplained cardiac death events. In that paper earlier this year, they had reported on four cases of individuals presenting with cardiac arrest or sudden cardiac death, attributable to concealed arrhythmogenic right ventricular cardiomyopathy with underlying mutations in the plakophilin-2 gene. In the letter from Chung et al, they report similar findings where individuals may first experience electrical phenotypes before manifesting structurally detectable disease. Indeed, in their response to this letter, Ingles et al report identification of an additional case since publication of their original article.                                            Taken together, this further strengthens the case for development of additional strategies to identify at risk individuals and predict and prevent disease events.                                            That's all for the papers for March 2019. Go online to check them out and follow us on Twitter @Circ_Gen to see new papers as they are published online. Thanks for listening. Until next month everyone. This podcast was brought to you by Circulation Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2019.  

This week on SELECT/START we check out the latest action RPG new age retro classic from Inti Creates called DRAGON: MARKED for DEATH! We also give our thoughts on the recent PS5 rumors as well as our thoughts on NETHERREALM'S latest MK 11 reveal. This and more on this edition of ACMG presents TALK TIME LIVE EXTRA!

Curtis and David celebrate life by yelling into microphones once more. This episode enjoyed, briefly but powerfully, the stylings of Neil Warren. Owner and operator of Alpine Threadworks, ACMG ski guide, and bringer of six-packs. Here's Neil doing his thing on a mountain: UNFORTUNATELY... Neil was forced to leave the episode early due to a family emergency. So our two heroes have filled the air with talk of a gigantic Cow, the Calgarian who made 52 different gins and we played our guest's lightning round against each other. Once again, we deliver what you crave. *UPDATE: EVERYONE IS SAFE AND OKAY*   Notable Links Spawn Bicycles, fancy kids bikes The grim revelations of scientists misusing CRISPR technology. The angry retort of the co-inventor of CRISPR when she heard what China was up to... The dude with all of this friggin' GIN We remember people's names! Hi Scott Felter of Porcelain Rocket   And here's a photo Crom took while shooting at Hexagon Game Cafe. ENJOY YOURSELVES.

This week fans all around the world learned the sad news of the passing of the legendary writer and comic book icon Stan Lee.  To honor and celebrate his contributions this episode will dedicate itself to acknowledging the 5 reasons to cherish what Stan has done for the world. We also have some news in the world of ACMG including the controversial comments of Bill Maher and Armie Hammer in reference to Stan Lee's passing. This and much more on this special edition of TALK TIME LIVE. 

In the spirit Thanksgivings coming soon, we will start the first of four episodes talking about the 5 fandoms that we are thankful for having come across in our lives and why. Our first will be based on anime. Find out what made the cut as well as the feedback from our ACMG members who talk about what anime they are thankful for as well. Plus all of the news and more this week as A.C.M.G. presents TALK TIME LIVE.

Jane Ferguson:                 Hello, welcome to Getting Personal: Omics of the Heart. It is June 2018, and this is podcast episode 17. I'm Jane Ferguson, an assistant professor of medicine at Vanderbilt University Medical Center, and a proponent of precision medicine, genomics, and finding ways to prevent and treat heart disease. Jane Ferguson:                 This podcast is brought to you by Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. Jane Ferguson:                 For our interview this month, early career member, Jennie Lin talked to Beth McNally about science and careers in genomic medicine. We'll have more on that later but first I want to tell you about the cool papers we published in the journal this month. Jane Ferguson:                 First up, Orlando Gutierrez, Marguerite Irvin, Jeffrey Kopp, Cheryl Winkler, and colleagues from the University of Alabama at Birmingham, and the NIH, published an article entitled APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults. This study was conducted in over 10 thousand participants of the Reasons for Geographic and Racial Differences in Stroke, or, REGARDS Study. They examined associations between APOL1 variants and incident coronary heart disease, ischemic stroke, or composite CVD outcome. Because there are coding variants in the APOL1 Gene that are only found in individuals of African ancestry, these are hypothesized to contribute to the disparities in cardiovascular and renal disease in African Americans. Jane Ferguson:                 The authors found that carrying the risk variants was associated with increased risk of ischemic stroke, but only in individuals who did not have diabetes, or chronic kidney disease. They hypothesize that because diabetes and kidney disease already increase CVD risk, the variant does not have an additional effect on risk in individuals with existing comorbidities. But, it contributes to small vessel occlusion and stroke in individuals without diabetes. Jane Ferguson:                 They also found that the magnitude and strength of the association became stronger in a model adjusted for African ancestry, suggesting an independent effect of the APOL1 risk variants. Jane Ferguson:                 While future work is needed to study this more, this is an important step in understanding the complex relationship between APOL1 and disease. Jane Ferguson:                 Next up, Daniela Zanetti, Erik Ingelsson, and colleagues from Stanford, published a paper on Birthweight, Type 2 Diabetes, and Cardiovascular Disease: Addressing the Barker Hypothesis with Mendelian Randomization. The Barker Hypothesis considers that low birthweight as a result of intrauterine growth restriction, causes a higher future risk of hypertension, type 2 diabetes, and cardiovascular disease. However, observational studies have been unable to establish causality or mechanisms. Jane Ferguson:                 In this paper, the authors used Mendelian Randomization as a tool to address causality. They used data from the UK Biobank, and included over 237,000 participants who knew their weight at birth. They constructed genetic predictors of birthweight from published genome wide association studies, and then looked for genetic associations with multiple outcomes, including CAD, stroke, hypertension, obesity, dyslipidemia, dysregulated glucose and insulin metabolism, and diabetes. Jane Ferguson:                 The Mendelian randomization analysis indicated that higher birthweight is protective against CAD type 2 diabetes, LDL cholesterol, and high 2 hour glucose from oral tolerance test. But, higher birthweight was associated with higher adult BMI. This suggests that the association between low birthweight and higher disease risk is independent of effects on BMI later in life. While the study was limited to a well nourished population of European ancestry, and would need to be confirmed in other samples, and through non-genetic studies, it suggests that improving prenatal nutrition may be protective against future cardiometabolic disease risk. Jane Ferguson:                 Laura Muino-Mosquera, Julie De Backer, and co-authors from Ghent University Hospital, delved into the complexities of interpreting genetic variants, as published in their manuscript, Tailoring the ACMG and AMP Guidelines for the Interpretation of Sequenced Variants in the FBN1 Gene for Marfan Syndrome: Proposal for a Disease- and Gene-Specific Guideline. Jane Ferguson:                 With a large number of variants being uncovered through widespread sequencing efforts, a crucial challenge arises in their interpretation. The American College of Medical Genetics and Genomics, and the Association for Molecular Pathology put forward variant interpretation guidelines in 2015, but these were not tailored to individual genes. Because some genes have unique characteristics, the guidelines may not always allow for uniform interpretation. Jane Ferguson:                 In their manuscript, the authors focused on variants in fibrillin-1 that cause Marfan Syndrome, and reclassified 713 variants using the guidelines, comparing those classifications to previous in-depth methods which had indicated these variants' causal or uncertain significance. They find 86.4% agreement between the two methods. Jane Ferguson:                 Applying the ACMG, AMP guidelines without considering additional evidence may thus miss causal mutations. And it suggests that adopting gene specific guidelines may be helpful to improve clinical decision making and accurate variant interpretation. Jane Ferguson:                 Delving deeper into FBN1 and Marfan Syndrome, Norifumi Takeda, Ryo Inuzuka, Sonoko Maemura, Issei Komuro, and colleagues from the University of Tokyo examined the Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome. They evaluated 248 patients with pathogenic, or likely pathogenic, FBN1 variants, and examined the effect of variant subtype on severe aortopathy, including aortic root replacement, type A dissections, and related death. They found that the cumulative aortic event risk was higher in individuals with haploinsufficient type variants, compared with dominant negative variants. Jane Ferguson:                 Within individuals with dominant negative variants, those that affected Cysteine residues, or caused in-frame deletions, were associated with higher risk compared with other dominant negative mutations, and were comparable to the risk of the haploinsufficient variants. These results highlight the heterogeneity and risk of the FBN1 variants, and suggest that individuals with haploinsufficient variants, and those carrying dominant negative variants affecting Cysteine residues or in-frame Deletions, may need more careful monitoring for development of aortic root aneurysms. Jane Ferguson:                 Lydia Hellwig, William Klein, and colleagues from the NIH, investigated the Ability of Patients to Distinguish Among Cardiac Genomic Variant Subclassifications. In this study, they analyzed whether different subclassifications of variants of uncertain significance were associated with different degrees of concern amongst recipients of genetic test results. 289 subjects were recruited from the NIH ClinSeq Study, and were presented with three categories of variants, including variants of uncertain significance, possibly pathogenic, and likely pathogenic variants. Participants were better able to distinguish between the categories when presented with all three. Whereas, a result of possibly pathogenic given on its own, produced as much worry as a result of likely pathogenic. The authors conclude that multiple categories are helpful for subjects to distinguish pathogenicity subclassification, and that subjects receiving only a single uncertain result, may benefit from interventions to address their worry and to calibrate their risk perceptions.  Jane Ferguson:                 Erik Ingelsson and Mark McCarthy from Stanford, published a really nice review article entitled Human Genetics of Obesity and Type 2 Diabetes: Past, Present, and Future. Over the past decade, we've had a lot of excitement, optimism, and also disappointment in what genome-wide association studies can deliver. Doctors Ingelsson and McCarthy do a great job laying out the history and the successes in the field of genetic interrogation of obesity and diabetes, as well as acknowledging where reality may not live up to the hype, what challenges remain, and what the future may hold. They also have a figure that uses an analogy of a ski resort to emphasize the importance of taking a longitudinal perspective. And I would argue that any paper that manages to connect apres-ski with genomics is worth reading, for that alone. Jane Ferguson:                 Robert Roberts wrote a perspective on the 1986 A.J. Buer program, pivotal to current management and research of heart disease. Highlighting how the decision by the AHA in 1986 to establish centers to train cardiologists and scientists in molecular biology, has led to huge advances in knowledge and treatment of heart disease. Jane Ferguson:                 Finally, rounding out this issue, Kiran Musunuru and colleagues, representing the AHA Council on Genomic and Precision Medicine, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiology and Intervention, Council on Peripheral Vascular Disease, Council on Quality of Care and Outcomes Research, and the Stroke Council, published a scientific statement on Interdisciplinary Models for Research and Clinical Endeavors in Genomic Medicine. Jane Ferguson:                 This paper lays out the field of cardiovascular research in the post genomic era, highlights current practices in research and treatment, and outlines vision for interdisciplinary, translational research and clinical practice, that could improve how we understand disease, and how we use those understandings to help patients. Jane Ferguson:                 Our guest interviewer today is Dr. Jennie Lin, an Assistant Professor at Northwestern Universities Feinberg School of Medicine, and the incoming Vice Chair of the Early Career Committee of the AHA Council on Genomic and Precision Medicine. As an aside, Jennie is a great person to follow on Twitter for insights into genomics and kidney disease, and as a bonus, she also posts the occasional dog photo. So she's well worth following just for that. You can find her on Twitter @jenniejlin. As you'll hear, Jennie talked to Dr. Beth McNally about her view on genomic medicine, and Beth also shared some really great practical tips for early career investigators building their independent labs. So make sure you listen all the way to the end. Take it away Jennie. Dr. Lin:                                  Thank you for tuning in to this edition of Getting Personal: Omics of the Heart, a podcast by the Genomic and Precision Medicine Council of the American Heart Association, and by Circulation: Genomic and Precision Medicine. Today I am joined by Dr. Elizabeth McNally, the Elizabeth J Ward Professor of Genetic Medicine, and director of the Center for Genetic Medicine at Northwestern University. Beth, thank you for taking time to chat with all of us. Dr. McNally:                       Happy to be here. Dr. Lin:                                  As a successful physician scientist, you have been interviewed in the past about your life, your scientific interests, and advice for budding investigators. I don't want to rehash everything you have already stated beautifully in an interview with Circ Res, for example. But instead wanted to focus more on your views of genetic medicine and genome science today. Dr. Lin:                                  So you mentioned in that prior Circ Res interview that you started your laboratory science training and career during college, when you participated in a project focused on genetic variation among children with muscular diseases. What have you found to be most interesting about the process of identifying functional genetic variants back then, and also that on-going work now. Dr. McNally:                       Well, I think over the years I've been doing this is the tools have gotten so much better, to be able to actually define the variants much more comprehensibly than we ever could in the past. And then also to be able to study them, and very much to be able to study them in context. And so I look at the revolutions in science that will cause people to look back on this era as the era of genetics. It began obviously with PCR, we couldn't have gotten anywhere without that. Dr. Lin:                                  Right. Dr. McNally:                       And then you leap forward to things like next generation sequencing, and IPS cells, and now CRISPR/Cas gene editing. And to realize that the last three happened within a decade of each other, is going to be so meaningful when you think about the next few decades, and what will happen. So being able to take an IPS cell and actually study a mutation or a variant in context of that patient, the rest of their genome, is really important to be able to do. Dr. Lin:                                  Okay, Great. And so, where do you envision ... with taking say for example, this next gen. technology, CRISPR/Cas9, studying variants in an IPS cell, for example. How do you envision this really revolutionizing the study of human genetics for patients? And how far do you think we've come in fulfilling that vision, and what do you think should be our focus going forward? Dr. McNally:                       I think broadly thinking about human genetics we're really very much still at the beginning, which I know is hard to say and hard to hear. But, we've spent a lot of the last 15 years very focused on that fraction of the genome that has high frequency, or common variation, through a lot of the GWA studies. With those common variants, we had a lot of associations, but relatively small effects of a lot of those, causing a lot of people to focus on the missing heritability and where we might find that hiding. And of course, now that we have deep sequencing, and we have deep sequencing where we've really sampled so much more of the genome, and from so many more people, I think we're just at the beginning of really appreciating that rare variation. And beginning again to really appreciate that 80-85% of the variation that's in each of our genomes is really characterized as rare. Dr. McNally:                       And so we really each are quite unique, and that when we understand a variant we do have to understand it in the context of all that other variation. So computationally that's very challenging to do. Obviously requires larger and larger data sets. But even in doing that, you are not going to find exact replicates of the combinations that you see in any one individual. While I know everybody would love that we're going to have the computational answer to all of this, it's still going to come down to a physician and a patient and making what you think is that best decision for the patient, based hopefully on some genetic data that helps inform those decisions. Dr. Lin:                                  Right, right. So it kind of gets into this whole concept of precision medicine, which has gained a lot of popularity and buzz in recent years, and Obama has really brought it to the forefront in the public arena. You mention rare variants in ... finding rare variants in each patient, for example. And moving a little bit away from some of the common variants that we find in GWAs. What does it mean for a patient to have a rare variant and come see you in your cardiomyopathy clinic, is it going to be precision for that patient, or suing rare variants among many different individual patients to try to find function for a gene? Dr. McNally:                       It's a great question. So I think the first way we approach it is, it depends who's asking the question. So if it's somebody who comes to me who has cardiomyopathy, or has a family history of cardiomyopathy and sudden death, that's a very different question to ask what's going on with their rare variants, for example in cardiomyopathy genes. Now if you translate that over to, I have a big population of people, I don't particularly know what their phenotype is, and I see rare variants for cardiomyopathy, those are two fundamentally different questions. So we very much know a lot about how to interpret rare variants for cardiomyopathy in the context of a patient or a family who has disease, and I do emphasize the latter part of that, the family, working with families and seeing how variants segregate within families. We interpret that very differently, and I think it's appropriate to interpret that very differently in that context. And that's completely different than again, going against what is the regular population, notice I'm not calling it normal population- Dr. Lin:                                  Right. Dr. McNally:                       ... but the general population that's out there. The first step in doing that is the list of the ACMG, American College of Medical Genetics, actionable genes. So this is an interesting question in and of itself. It's 59 genes, of course that list is too small, and it should be bigger than that, and ultimately that will happen. But to take a population based approach to those actionable genes, and looking across the population, finding someone who's got variants in, lets say our favorite genes MYH7, MYBPC3. Knowing what that risk means on a population level is very different than knowing what that means in the context of a patient who comes to you, who has that variant, runs in their family, and has clear disease. Those again, really two different questions, and we have to come up with what's the best practices on that, how to answer either of those questions. Dr. McNally:                       I think the first step working with patients and families who have known disease and have clear variants that segregate with disease, I think its very powerful. I think we've probably got close to a good decade of doing that already. It's incredibly useful for those patients and families. It helps us reduce their risk. It helps us treat them early, it helps us manage their arrhythmias. There's no question that that information is incredibly valuable, but we're still learning how to process that across the population, and how to answer that question for people who are coming who don't already have disease. Dr. Lin:                                  Right, right. That makes sense. And I guess that kind of plays into a follow up question about whether or not we need to test, or think about every variant of unknown significance in lab, and ... the- Dr. McNally:                       It's a great ... You know again, you always have to very carefully consider the context in which the question's being asked. So again, if you're talking about a relatively normal population, well, walking, healthy person, and you're seeing variants of uncertain significance, that's a very different question than somebody who's coming in to you with cardiomyopathy and has a highly suspicious variant of uncertain significance that falls right within the head domain of MYH7. We know a lot about that, and we can do a lot of interpretation in that case. Dr. McNally:                       However, I would say that to put too much value on what we do in the research lab ... Just putting a regulatory hat on for a second and thinking about it, there's nothing from a regulatory standpoint that really validates what we do in the research lab, to say that we can really fairly adjudicate a VUS or not. We can't do that, that's over-valuing what we do in research lab. Dr. McNally:                       So I think, how do we consider variants among certain significance? I think it's really important to recognize that it's exactly that, it's a variant of uncertain significance. And so when you're a clinician taking that to a patient, you have to approach it from the standpoint of saying, this is a variant of uncertain significance. Which means we don't know whether it's pathogenic, but we also don't know that its benign. Because I think right now what we've seen, a lot of clinicians, and even researchers, fall into the path of this believing that variant of uncertain significance is the equivalent of benign. That's not true. It is simply ... That is a rare variant, and we don't know whether it's pathogenic or non-pathogenic. And hopefully overtime we will learn more to better assess that, and better provide the interpretation of what that means in the context of that patient. Dr. McNally:                       It's a good conversation to have. It's important to recognize they're not necessarily pathogenic, but they're also not necessarily benign. Dr. Lin:                                  Mm-hmm (affirmative). So do you see a role, for example, when you see this variant of uncertain significance, is there a role to go back into lab, for example, and try to knock that mutation to IPSC's and test to see if its pathogenic? Or is that going a step too far? Dr. McNally:                       In some cases, that is the right thing to do. Because genetics is so powerful, genetics doesn't only give you the association of a gene with an outcome, and GWAs was fabulous at doing that ... giving us a lot of variants, and often nearby genes, sometimes far away genes, but linking genes to phenotypes, and that's very powerful. But specific variants can actually tell you a lot about mechanism, about how a gene and protein actually function, and how it functions when it's broken. And so, particularly where you can gain a lot from the research front in understanding mechanism, then I think it's really powerful to take those things to the laboratory and to use that to learn about mechanism. Dr. McNally:                       Sometimes you can do it to help adjudicate whether something's pathogenic or not, but again, I think we want to be cautious in doing that. Because what we do in the res ... I always like to say, "What we do in the research lab isn't exactly CLIA certified." Dr. Lin:                                  Right. Dr. McNally:                       There isn't anything magical about what we do, but we definitely ... It is so powerful what's available out there in terms of the genetic variants, and teaching us about how genes and proteins interact. And so I think it is such a rich resource of information right now. The things I bring back to the laboratory, and get my students and trainees excited about working on, is usually where I think we can gain something new about mechanism. Dr. Lin:                                  Right, right, right. Since you are a role model physician scientist, and you think about questions in lab that will ultimately benefit your patients, and you are a genetic cardiologist. What are your thoughts on doing genome editing as a possible therapy for your patients? It's a little bit of a loaded question [crosstalk 00:21:51], it's a little bit controversial. Dr. McNally:                       So I think, no doubt CRISPR/Cas9 gene editing is transforming what we do in the research setting. It's a fantastic tool. Is it a perfect tool? No. Anybody who has been using it a lot in the lab knows that it is much better than anything we've had before, but still quite limited in fidelity and efficiency. And so imagining that we are going to do that in patients is still pretty daunting to me. We do enough gene editing in cells to know that you have to select through an awful lot of cells before you get the one that has the exact variant you are trying to make. So that's not something we can tolerate in the human setting. But we're not there yet, we know that. Dr. McNally:                       Many of the disorders I see clinically are things that are autosomal dominant due to very precise single base-pair changes. And so envisioning how we're going to correct only one copy of an allele and do in a very precise manner, we don't have those tools available yet. Now on the other hand, if you look at a disease like one of the diseases I spend a lot of time on, Duchenne muscular dystrophy, where the majority of mutations are deletions. It's X-linked, it's male, so there's only one copy of the gene, and we know a whole lot about the structure and function of the gene. We know that if we take out this other part we can skip around that mutation and make an internally truncated protein. That's actually a very good use of gene editing, because it only requires making deletions. They don't need to be very precise, and there's only one copy of it that you have to do the gene editing on. Dr. McNally:                       So I see that being something in the near term that will happen, simply because the genetics positions it well to be something where that could be successful. The hard part is still how are we going to get the guides, and how are we going to get the Cas9 in safely into all the cells that need to be treated? And ultimately that lands us back at looking at what our delivery vehicles are. Which at this point in time is still viral delivery, and still has a lot of issues around can we make enough of it? Are people immune to it? So all those questions that come with viral delivery. So still lots of hurdles, but you can see some paths where it makes sense to go forward. Dr. Lin:                                  Very interesting. Okay great. Well thank you for providing your thought on human genetics and genome science. We're going to switch gears for the last portion of this podcast, and talk about your thoughts on career development issues for young investigators. At a recent AHA Scientific Sessions meeting, you participated on a panel that was assembled to provide advice to early career scientists. When you were starting out, what were some of the biggest challenges you faced when you were transitioning to independence and building your own lab, and what's your advice to those facing the same challenges today? Dr. McNally:                       Well, even though I did it quite a few years ago, many of the things are still the same. Transitioning to independence, I think is easier if you pick up and move and start in a new place. I think it's much easier to establish your independence when you're not in the same place as your mentor. That said, we have many more people who now stay in the same place as where their mentors were and we have many more approaches towards doing that. So I think people are much more open to both possibilities as being ways of doing that. But at some level it still comes down to starting your own lab, and you hopefully have been given some start-up resources and you have to think about how to wisely spend them, and how to really get things going. I don't think this is changed either. Dr. McNally:                       I usually tell people, don't just start in one area, if you can, start in two areas because things don't work, and sometimes things do work. In reality when you look at people who are successful, they're often working in more than one area. And so the sooner you start getting comfortable working in more than one area, that's a good thing. Now ideally, they should be areas that have some relationship to each other, and then feed each other in terms of information so that they grow off each other. But what does that practically mean? I always say, "Well if you can hire two people and start them on two different paths, that's a really good way to get going." And practical things like look at all different kinds of private foundations and things like that for getting some good pilot start up money to help develop new projects in the lab. And always be looking at how can these projects help me develop a bigger data package, that's going to put me in a good competitive position for example bigger grants and federal funding, and things along those lines. Dr. McNally:                       Very much a stepwise process. People want to shoot for the moon and get the biggest things first, but sometimes just focusing on the smaller steps which are definitely achievable and building your path towards those bigger steps is the smarter way of doing it. Dr. Lin:                                  That's great advice. You also mentioned recently that young investigators should try to have as many mentors as possible. What advice would you have for, in particular, early career genomics investigators, for finding these mentors passed the postdoc phase? Some of us get introduced at the postdoc phase to maybe some other collaborating labs, but those are really collaborations of our mentors per se. Dr. McNally:                       Well I think especially in the field of genetics and genomics, collaboration is key, and I will say one of the things that has changed over since I started doing this is there is a lot more understanding of the need to collaborate. Not so many years ago, it wasn't really an independent investigator went and started a lab, and it would be your trainees and the papers would have only those people on it. Dr. McNally:                       I think these days, the best science is where you've tackled a problem from multiple different directions, one or two of those being genetics, genomics directions. And then sometimes there's other ways that you've approached that scientific problem. And by necessity, that usually involves collaborating with other people. And your role is sometimes to be the coordinator of all those collaborators, and that's where again you might be in a senior author position then doing that. But your role sometimes is to be the good collaborator. And so when I look at people being successful right now, seven, eight years in to running their own lab, I like to see that they've been the organizer of some of those, that they've collaborated with people who are even senior to them, and that they've established those good collaborations, but that they've taken the leading role in doing that. But also that they've had middle author contributions, that they've been a good collaborator as well. Dr. McNally:                       And so, part of that is not being afraid to collaborate, and to recognize the value of doing that. And what's so great about doing that is you can collaborate with people at your same institution where you are, but you can also collaborate with people all over the world, and I think that's what we do. You go to where you need somebody who is using a technique or an approach that really helps answer the question you want to have answered. And so that's reaching out to people and really establishing again that network and good collaborators which you can do by a whole bunch of ways. You can do it by meeting somebody at a meeting, scientific meeting. You can do it through emails, phone calls, Skype, all sorts of different ways that you can reach out and collaborate with people. Dr. McNally:                       It is easier than ever to share data and share ideas, but that negotiation of how to establish the terms of the collaboration and how to make it be successful is a critically important part of being a scientist. And what we now know when we look at the promotion process, is people who do that effectively, that's a really important mark of being a successful scientist, and marks them as somebody who should be promoted through the process. So great. Dr. Lin:                                  Yeah. No I agree. Certainly with the direction science is moving, it's definitely very difficult to work in a siloed manner. Dr. McNally:                       Yeah. Well you won't get very far. You'll be able to have some really good first ideas, and show some proof of principle approaches. But to really, really address an important scientific problem, we know that you have to see those signals using multiple different methods. And once you have five different ways showing you that that's the right answer, then you're much More confident that you've gotten to the right answer. Dr. Lin:                                  Right. Alright, so I think we're going to wrap up. Do you have any other final thoughts for any other young investigators or genomics researchers listening to this podcast? Dr. McNally:                       It's a great time to be doing genetics and genomics, and particularly human genetics, where we now finally have all this information on humans, and we'll have even more of it in the future. So I think humans are coming close to becoming a real experimental system. Dr. Lin:                                  Excellent. Alright well thank you so much for your time. It was a pleasure having you on this podcast. Dr. McNally:                       Great. Thank you for doing this. Jane Ferguson:                 As a reminder, all of our original research articles come with an accompanying editorial, and these are really nice to help give some more background and perspective to each paper. To read all of these papers, and the accompanying commentaries, log on to circgenetics.ahajournals.org. Or, you can access video summaries of all our original articles from the circgen website, or directly from our YouTube channel, Circulation Journal. And lastly, follow us on Twitter @circ_gen, or on Facebook, to get new content directly in your feed. Jane Ferguson:                 Okay, that is it from us for June. Thank you for listening, and come back for more next month.  

What are the most inspiring takeaways from the scientific sessions? How does NGS genetic testing provide clinicians a better tool to diagnose patients? In this podcast, Genetic Services Consultant Adam Beres and Clinical Interpretation Team Leader Eveliina Salminen discuss the highlights of the 2018 Annual Clinical Genetics Meeting (2018) organized in Charlotte, NC, USA. Eveliina addresses the most interesting topics from the scientific sessions, e.g. how NGS genetic testing has provided clinicians with a powerful tool to better diagnose patients.

Jane Ferguson:                Hi, everyone. Welcome to Episode Four of Getting Personal: -Omics of the Heart." I'm Jane Ferguson, an assistant professor at Vanderbilt University Medical Center. This month, we have a special feature from early career member, Andrew Landstrom, who went to the Heart Rhythm Scientific Sessions in Chicago earlier this month and talked to some of the scientists who presented their research. So listen on for interviews Andrews conducted with Anneline te Riele, discussing the challenges and opportunities related to incidental findings in genetic testing, with Ernesto Fernandez, describing his research into whole exome sequencing and Long QT syndrome, and with David Tester, discussing novel variance and pathway analysis in Sudden Infant Death Syndrome. Andrew :                           My name is Andrew Landstrom and I am from the Baylor College of Medicine Department of Pediatrics' section on Cardiovascular Disease. I'm here at the 2017 Heart Rhythm Society Scientific Sessions. Anneline, will you tell us a little bit more about yourself, and what brought you to HRS? Anneline:                          Sure. So my name is Anneline Te Riele, I am a physician from The Netherlands. I finished my medical training in 2012 basically, in The Netherlands, and I started doing a PhD on ARVC in a combined project of our Netherlands patient as well as a group at Hopkins. So what brought me to HRS? I think of course the science. There's a lot of very good science. Actually, I think it's the best meeting for my purposes. Andrew :                           Absolutely. So will you just start by telling us a little bit about the spectrum of genetic testing in the clinic and about both the opportunities and the challenges that it brings? Anneline:                          Sure. So what we do in clinic, and I think this is really the challenge that we're facing currently, is we have moved from just testing on gene or one small panel of genes to bigger panels and then to whole exome or even whole genome sequencing. And I think the good part of that is that in certain cases, certain well-selected cases, you'll get a higher change of actually finding that gene that is responsible for disease.                                            On the contrary, it also leads to a lot of incidental findings. So findings that you were not expecting based on the phenotype of the patient and then you need to deal with those abnormalities that you've found and that brings on a lot of challenges as well for the family but also for us as physicians. Do we then need to screen those families, what do we do with this patient, do we treat them with medical therapies or drugs or do we give them ICDs? That kinds of question. So that I think is a virtually important part of what we're currently dealing with in clinical practice. Andrew :                           It does seem to be a very widespread problem. And here in the US of course we have the American College of Medical Genetics guidelines about reporting a variance. How do you think that that plays into the increased genetic uncertainty here in the US at least? Anneline:                          So that's a great questions. In 2013, the ACMG produced a guideline on which genes to report if you find these incidental findings. So 24 of these genes, and that's actually a big number, 24 of these genes are cardiovascular genes and that's mainly because changes in cardiovascular genes may detrimental effects down the line and really cause death or certain morbidities that are really important for the patient so we do need to deal with that.                                            And the problem with the ACMG guidelines and especially the pathogenicity guidelines is that they require two aspects. They basically require first that the variant was seen before in other cardiomyopathies or in this case other patients with disease. And that's really difficult for cardiomyopathy genes because these are large genes, they have a lot of novel or private mutations in there, so it's really hard to fulfill that requirement of having been seen before.                                            And the second thing is that the ACMG guidelines require functional studies as another proof of evidence of pathogenicity and of course, I think we would all like to do that in all of our patients, but it's just not feasible for financial purposes and all that. So that's a problem that we're facing. There are options and solutions but I think we'll talk about that later, but yeah, I think that's a problem that we're facing. Andrew :                           So on the one hand you have the ability to make a diagnostic decision based on a clear finding, but oftentimes the threshold to calling it a clearly pathologic variant is very high and oftentimes it never rises to that so it becomes more genetic uncertainty. Anneline:                          Yeah. I think that's basically right. And of course in an ideal world, we'll have certainty and say this is likely or this is definitely pathogenic, and this is likely or definitely benign, but in the real world, really, I think maybe even 80, 90% of the cases were in that gray zone in between and we need to deal with that. Andrew :                           Yeah, yeah. And you had some great resources that both scientists and clinicians alike can apply to these unknown, uncertain variants that might clarify things at least a little bit, and what are these tools? Anneline:                          So of course, from a traditional perspective, we have always looked at in silico predictive programs, we'll look at segregation data, and I think they're all very important, but they all have limitations, so for example, in silico predictive programs, they likely overcall mutations deleterious and segregation data is nothing more than evidence of pathogenicity of a locus to a disorder, not necessarily that variant, so the new things that are on the horizon, and a thing that could be the future of [inaudible 00:06:04] interpretation is collaborative project so really we should be collaborating, we should not be having our own little islands. The collaboration is the key here.                                            And collaborative efforts in the US have been for example, ClinVar and NHLBI funded effort, as well as ClinGen and ClinGen, or Clinical Genome, is perhaps the, at least it claims to be, the authoritative central resource to go back to that curates variants as being pathogenic yes or no. And I think these databases, ClinVar finally has a database entry, so the variants will be in ClinVar, but ClinGen provides an expert panel of individuals who will curate these variants as being pathogenic yes or no. I think that is a central resource that we should all be aware of. I know these are not the only ones, there are other collaborative efforts out there.                                            I mean, there are ways to connect clinicians, so for example, Match Maker Exchange is a website that you could use to enter your variant and the phenotype of the patient and you submit your own information and then you'll get matches in other databases, but not only your own match shows up. So if, say, two years later, another physician comes up and looks for the same variant, you'll get a pop up, which will actually be very nice for these clinicians to get in touch. So that's, I think, the feature ... future of variant interpretation is collaboration. That's basically my, I think my main important message here. Andrew :                           I think that's absolutely right. I think this has become sort of a big data question that requires many perspectives, and a lot of resources to be able to curate accurately. What are some of the limitations of these tools that you've seen that kind of, you have to keep in mind in terms of trying to determine whether a variant is truly pathologic or not with a patient that you have sitting in front of you? Anneline:                          So that is, I mean, of course, there's many limitations in the things that we currently do because there's so much that we don't know. But for example, to give you an example, ClinVar I think, is one central resource that we should all be aware of and if you go to ClinVar, there is actually data from two years ago, and I'm sure the numbers are high if we would look now, but if we look in ClinVar two years ago, we already saw that of the, say 120,000 variants that were in the database, 21% of these variants were called VUSes but if you look at these variants, 17% of the cases, the labs or the individual submitters of ClinVar didn't agree on the actual classification of that variant.                                            So the limitations that we all should be aware of is that there is not one single solution and you should look for evidence and really research your variants. So look at Popmap, look at what is out there, look the patient of course, look at the clinical phenotype, does it match what you think the gene should be doing or not, or is it completely unrelated? And then of course search these databases but be aware of the fact that there may be errors there.                                            Another thing I want to highlight too is that we typically go to population databases, so Exome Variant Server, ExAC, I think these are very popular databases that we use to look at the frequency of variants in a selected population. But really these databases may have sub-clinical disease patients, so I know ExAC has three NYBPC-3 mutations that are known to cause HCM, so this is something to keep in mind. There's not a gold standard truth if you open these databases, but you should have multiple pieces of information when interpreting your variant. Andrew :                           And that's a good point. I think with a lot of these cardiomyopathies and channelopathies, particularly some of the more frequent ones, when you have a database of 60,000 people, at least a couple of them are going to have disease. Anneline:                          Yeah. I think that is part of the problem. I mean HCM is pretty prevalent, I mean one in 500 individuals likely, I mean these are recent numbers, has the disease. So I think the cutoff of a minor allele frequency of five percent, which is in the ACMG guidelines, I think is way too high for this disease. So this is what the cardiovascular expert panel of ClinGen has done, so they ... This is, ClinGen, as you might know, Clinical Genome, is a one-on-one team of curators that know the framework of ClinGen and then there is disease experts that are very well accustomed with the disease and the genes associated with it. So they provide teams and these teams work together, and the cardiovascular expert group has recently published a modified, or customized, ACMG guidelines on how to deal with the intricacies of the cardiomyopathies and for example, NYH-7 which is the first genotype deposed in ClinGen or in ClinVar finally.                                            So they modify that cutoff, the minor allele frequency of five percent, which is the BA-1 ACMG guideline cutoff, they changed that to 0.1% and I think that's exactly what you were saying, that is important to keep in mind, some of the cardiomyopathies are way more prevalent so you should not consider that if you see it in a population database that you think that it's, then it's normal, it's not necessarily the case because this is a prevalent disease. Andrew :                           Yeah, and particularly when commercial genetic testing companies all can't agree that a variant is bad, and we all can't agree that a healthy variant may or may not be good, there is definitely a lot of genetic uncertainty there. Anneline:                          Exactly, exactly. Andrew :                           Now, whole-exome sequencing certainly has its role clinically, even with that genetic uncertainty that we spoke about, but it has a clear role in genetic discovery as well. Anneline:                          Sure. Andrew :                           And you were part of a very recent paper, and you led a very long list of authors, speaking more about your collaborative approach to genetics research that evaluated a novel substrate for ARVC, is that correct? Anneline:                          Yes. So this is something I'm actually pretty proud of. As you said, it's a collaborative effort, so it literally take a village to do these kind of studies and we're lucky enough to collaborate with a lot of people who are interested in the same topic. So what we did ... and I metnioned to you in the beginning, I come from the ARVC field ... So what we did is we had one ARVC patient that was discovered by whole-exome sequencing to carry an SCN5A variant and we, in and of itself, found that that was very interesting, because SCN5A, as you know, has been associated with Brugada syndrome predominantly but many other cardiomyopathies as well, so DCM, even ACM. There's been a lot of controversy about SCN5A in that matter.                                            So the computational data, the population data, it all pointed to the fact that this variant may be pathogenic, but we weren't really able to connect those dots just yet. So we then collaborated with the group in NYU with Mario Delmar, who did, first of all, functional studies on the sodium channel, but what was nice is that he was able to use his novel method of super-resolution microscopy which is a way in which we can look at the nano-scale structure of the cardiomyocytes, or really the small, small levels of molecules that you see in these cells. And what we did is we found that not only NAV1.5 which is the gene product of SCN5A but also [inaudible 00:13:53] which is an adherence structure molecule, which links the cells together was actually less present in our ARVC patient compared to the control. And this was in the IPS so cardiomyocyte molecule, which we corrected using CRISPR-Cas9 technology so I think at least in current practice, on of the best pieces of evidence that we can get.                                            So I think this shows that our SCN5A variant, I mean, in this case, probably really was pathogenic, but also in a pathophysiological standpoint, explains to us how SCN5A mutations, which are typically thought to be only affecting the sodium channel, can also lead to cardiomyopathy phenotype which has implications beyond the ARVC world, but also in DCM I think this is a nice finding of collaboration that I think ... I hope more people will look into this. Andrew :                           Absolutely I think the trouble with SCN5A is exactly like you were saying, it's been implicated in Long QT, Brugada Syndrome, SIDS, [inaudible 00:14:57], now ARVC, and even nodal disease, like sinus syndrome and things like that. So the ability to show sort of mechanistically, that while you have a change in your sodium channel gating that you also have a change in the way that the cells can connect with each other and form contractile force is, I guess, key to your study. Anneline:                          Yeah, yeah. I think this really, I mean, I'm hoping at least, it was also finally published in a journal that looks more into functional studies, so not necessarily only genetics, and I think we need to work closely not only on the genetic side, but look closely at the pathophysiological standpoint for gene discovery purposes because this will really explain to us why one gene is implicated in one disease, and also it points to possible directions to perhaps stop the disease process and treat these patients, which I think is vital in our clinical practice. Andrew :                           So are SCN5A mutations in ARVC a common finding or are they rare? Anneline:                          So they are pretty rare. I mean, we do find them every now and then and maybe they're modifiers. So what we did to follow up on that one individual, we check 281 ARVD patients who were screened just by regular screening, not by whole-exome but we did a targeted screening of SCN5A and we found five variants in these 281 patients, so that's two percent. I mean, it's still rare, but it is as rare as any other minor gene causing ARVC, but it is a rare feature, so I mean, I think it could be a player. And interestingly, the phenotype didn't change much. It wasn't really different from the ARVC patients without an SCN5A mutation which is reassuring.                                            What we also saw is that the prevalence of mutations in those with desmosomal mutations. So ARVC is, as you know, typically associated with diseases or mutations in the desmosome. It was more often seen in those without a desmosomal mutation. That was almost double as frequent as in those with a desmosomal mutation. So it does give us some direction to the fact that this may be a player out there. I mean of course it's not Plakophilin-2 which is the major player, I think, in ARVC, but I think it may cause a, at least a certain form of cardiomyopathy of arrhythmogenic cardiomyopathy that we need to be aware of. Andrew :                           And how do you think your new discovery of SCN5A being associated with ARVC, how do you think that plays into the bigger discussion we were having about expansive genetic testing and what that may mean for a patient as far as diagnostic utility but also limitations of variant interpretation? Anneline:                          That's a great question. So I think we should be cautious of saying this gene causes only this disease, and I think this is a common feature not only in ARVC but in a lot of cardiomyopathies and even in channelopathies. I think the concept of one gene causes one disease is outdated. We know that multiple genes have multiple effects and this SCN5A, of course the gene product is NAV1.5 which is the major alpha subunit of the sodium channels so it is really not the canonical function of SCN5A or NAV1.5 that causes cardiomyopathy here but it's a non-canonical function so I think we should be aware of the fact that gene products have different functions and that there can be overlap of the cardiomyopathies. So of course I think we should be screwing SCN5A in our ARVC patients and I'm hoping a lot of labs and a lot of physicians are already doing that, but it's really not the only thing that is associated with ARVC. So that's important to keep in mind. Andrew :                           What do you think the next steps are for sort of broadening the implication of your finding? Anneline:                          So what we are doing currently, and is a little bit of a sneak peek, because this data is not really out there yet, but we have, in this cohort, we found these five variants in 281 individuals, and we're currently working on one of these individuals to get another IPSO cardiomyocyte cell line and look into the functional components to that. And interestingly, this variant, that exact variant in that ARVC patient was also found in a Brugada Syndrome patient. So wouldn't it be nice to actually set them side by side and see what the differences are?                                            Of course this is a little bit of a future music, if you know what I'm saying, like this is something that we don't have just yet, but I think what we need to figure out is how epigenetic or environmental factors play into this field and to explain how one gene or one variant, even, can cause opposite functional effects in different phenotypes. Andrew :                           What do you think is needed to help clarify some of the genetic uncertainty you see clinically? Anneline:                          I think a lot of collaboration, a lot of money, quite frankly. I think we need to ... I mean, the functional data is really helping us not only for understanding that single variant, but also for gene discovery, and as I said, for treatment down the line, that is necessary, and I think the variant of uncertain significance, I mean, if we all live on our little islands and only do our little practices, then we're not going to go a lot further. So we need to work together to understand what your patient has in this variant, my patient had in that variant, and this is our phenotype, so we need to connect those dots to be able to make certain conclusions. Andrew :                           Well, I'm all for collaboration, as well as additional money, that's good. Anneline:                          Good. Andrew :                           Well, thank you so much for spending time with us. Anneline:                          Sure. Andrew :                           And again, congratulations on a wonderful presentation. Anneline:                          Thank you very much. Andrew :                           I'm joined by Dr. Ernesto Fernandez from the Baylor College of Medicine to talk about his research project. Ernesto, I'm wondering if we can just start by introducing yourself and what your project is. Ernesto:                            I am a second-year pediatric resident, I'm applying to a cardiology fellowship right now and I'm interested in, obviously, all aspects of pediatric cardiology. We're trying to figure out whether testing for Long QT genes or Long QT syndrome is actually warranted in otherwise healthy individuals. We're trying to see what the yield is on these testings, specifically whole-exome sequencing. Andrew :                           And I think this project really hits on an important point, whereby, because we've been able to interrogate the genome more comprehensively with clinical testing, that we've run into more incidentally identified variants. And these variants can pop up in genes, like the genes responsible for Long QT syndrome. Talk a little bit more about these variants, what the implication is of finding these variants incidentally, and what your project hoped to target as far as the diagnostic value of these variants. Ernesto:                            Yeah. So I guess the answer to your first question is that we are coming up with these marvelous new techniques of analyzing the genome and now we're using whole-exome sequence testing to look up is someone has any exome that's abnormal and this has caused a huge problem whereby we're now finding all these variants that we don't really know what they mean. We call them variants of undetermined significance.                                            Our study is basically premised by the fact that if you have no underlying suspicion for any arrhythmic disease, there's really no need or no indication to be referred for whole-exome sequencing testing, given that the most likely result is a variant that we don't really know what it means. And it's probably going to be benign. Andrew :                           So on the one hand, you have a well-established gene panel that's being used for diagnostic purposes with you index of suspicion being high for Long QT syndrome versus something like a whole-exome gene screen where somebody may not be thinking about Long QT syndrome as a diagnosis and have low pre-test suspicion but then comes back with a variant found in these genes sort of incidentally. Is that sort of the dichotomy you're drawing? Ernesto:                            Yeah. I think the best way of explaining it is through Bay's Theorem whereby if you have someone with a high index of suspicion when you start off to have sudden cardiac death, a family history of an arrhythmic disease, and you get a test for it, such as a gene panel for Long QT syndrome, and they come up with a positive test result, then you're going to say, "Oh. I should probably evaluate this further," whereas if you have someone who has some dysmorphism, they have delay, they might have seizures, but there's no family history of sudden cardiac death, no personal history of syncope, then there's really no need to send off this big gun, the whole-exome sequence, because you're likely to either get a normal variant or you're likely to get a variant that we don't know what to make of. Andrew :                           So I think, Ernesto, that nicely summarizes the clinical question that you had in mind. What was your hypothesis going into the study, and how did you seek to approach that hypothesis, sort of experimentally? Ernesto:                            So we came up with the hypothesis that if you have an incidentally identified variant within the whole-exome sequencing tests without any other clinical suspicion, it's likely to represent a benign finding. We went about by analyzing the data from the Baylor Miraca labs on the whole-exome sequencing data that they achieved, and we looked specifically at individuals who had gotten these tests and found to have a variant of undetermined significance, or had a pathologic variant for either one or all 17 of the genes for Long QT syndrome. We compared them to individuals who had known Long QT syndrome that had undergone genotype testing, and we [inaudible 00:25:21] these individuals from the literature. And we wanted to compare the whole-exome sequencing cohort to individuals who were otherwise healthy and had obtained a whole-exome sequence. So these are patients or individuals from the well-established ExAC database that are believed to be ostensibly healthy individuals. Andrew :                           So if I understand you correctly, you're comparing this unknown cohort, that being the rare variants found in whole-exome sequencing, against a positive control cohort of pathologic cases versus a negative control cohort of healthy individuals derived from the ExAC database to look for whether those west variants are more similar to the cases or the controls. With regards to the west cohort, what was the prevalence of individuals with these incidentally identified variants, how many did you find? Ernesto:                            So we actually found just about 49% of individuals had some variant in Long QT syndrome gene, and noted that about 12% of them had a mutation in the major causes of Long QT syndrome, and just over a third, or 36% had a mutation in the more rare causes of long QT syndrome. Andrew :                           That's a pretty surprising finding. So you're saying that one in two individuals who get whole-exome sequencing sent for whatever reason, have a variant in a Long QT-associated gene? Ernesto:                            That's what the data suggests. Andrew :                           And where did you go from here? Ernesto:                            So from there, we went onto compare the variant frequency between the case's cohort, those individuals with known Long QT syndrome, those individuals in our west cohort from the Baylor Miraca labs, and those individuals from the ExAC database who are otherwise healthy. So we noted that in our west cohort, there was about 13% of individuals who had a positive variant in the Long QT syndrome one through three genes, the major causes of Long QT syndrome. When we compare that to the ostensibly healthy individuals from the ExAC database, it was 12% in that study that had some variant in Long QT syndrome genes that are major causes of Long QT syndrome itself.                                            This was statistically similar, it was indistinguishable. And then when we compared it to the pathologic cases, it was actually about 50% of those cases who had a positive variant in a Long QT syndrome gene one through three. Andrew :                           So there was a relatively low frequency of individuals who had variants in one of the big three Long QT genes in both controls and the west cohort, and was obviously much higher among individuals with a diagnosis of Long QT syndrome. Ernesto:                            Yep. That's exactly what we found. Andrew :                           And where did you go from here? Ernesto:                            And then from there, we had a good idea that there was probably a big difference between cases and west, but we wanted to make sure, gene by gene, that there was no difference between our west cases and the ExAC database, the control cases. So we mapped each variant frequency by gene for the major causes of Long QT syndrome. There was no statistically significant difference between the west and the controls. Andrew :                           So the gene frequencies between the controls and the west were indistinguishable and very much different, both of them, it would seem, to the pathologic cases. Ernesto:                            Correct. Andrew :                           And you then looked at the position of these variants, the actual amino acid residues, correct? Ernesto:                            Yeah. So we looked at, for KCNQ1, KCNH2, and SCM5A, the three major causes of Long QT syndrome, one, two, three respectively, and we mapped out the amino acid positions where there was actually a mutation for each individuals. So the cases, controls, and pathologic cohorts. We determined the percent overlap between the west cohort and the controls and the percent overlap between the west cohort and the cases and noticed that for all three, there is a huge preference for west and control versus west and cases. Andrew :                           So if you're a west variant you're more likely to reside in the residue also occupied by a healthy individual variant as opposed to a pathologic variant? Ernesto:                            Yeah. Exactly. Andrew :                           And so what did you do next? You retrospectively looked at some of the charts of the patients who were seen at Texas Children's Hospital, correct? Ernesto:                            Mm-hmm (affirmative). So then we had 223 total individuals that had an incidentally identified variant within one of the major three genes, the Long QT syndrome genes. We looked at the reasons for their referrals and noticed that the vast majority of individuals were referred for some developmental delay, for some dysmorphism, for a non-cardiac cause, and then it was only about 23% of these individuals that actually had a reason for referral that was cardiac in nature. And less than on percent of individuals were referred for a solely cardiovascular reason. And we concluded that it's unlikely that these individuals were referred for a cardiac reason, as the data suggests, and that as a result, the index of suspicion for an arrhythmia is likely lower in these individuals. Andrew :                           And what did you find when you looked at the charts of those individuals? Ernesto:                            We had EKG data for a good number of them, and we excluded individuals who obviously had no EKG data, and we excluded individuals who had some congenital abnormality and then anyone with any other arrhythmia that would make the QTC interpretation more difficult, such as interventricular conduction defects.                                            We ended up with 62 individuals and 61 of them had a normal QTC, so there was no evidence of QT prolongation at all. There was one individual who was left who had borderline elevated QTC of 460, which was our cutoff for borderline elevation and this individual had actually been seen by pediatric cardiology at Texas Children's Hospital and found to have ... a history of syncope and it was found to be non-cardiogenic in nature. Andrew :                           So matching the variant data which suggested that you had likely found background variation in the west, you found no evidence of Long QT syndrome in these individuals who had variants in Long QT genes. Ernesto:                            That's correct. So, the overall percent was very similar between the healthy individuals and the west individuals. The variant frequencies were almost indistinguishable, and then the variant co-mapping for all, for both the west and the controls, was preferential to the western cases. So that kind of matched what we found in our study, that there was no clinical suspicion or clinical diagnosis of Long QT syndrome in these individuals who had been found incidentally. Andrew :                           Well that sounds to me to be a pretty big finding. Ernesto:                            Yeah. I think it's pretty important to get this information out there. Andrew :                           So what do you think the take home message for your study is? Ernesto:                            I think the take home message is if you don't have a suspicion of Long QT syndrome or of an arrhythmia, there's low likelihood that such a big gun test as the whole-exome sequence is likely going to change your mind. Andrew :                           So Ernesto, what would you advise a cardiologist who maybe gets a patient in clinic with a chief complaint of a VUS in a Long QT associated gene picked up on west, what would you advise based on your study findings? Ernesto:                            They're going to have to determine their own pre-test suspicion. They're going to have to get a good history and physical, probably get a baseline EKG to determine what the QTC intervals are, and if there's really no other clinical suspicion for Long QT syndrome, they're likely to be able to provide reassurance at that point in time. Andrew :                           Ernesto, what do you think the next steps are for this project, and what do you think still needs to be done in the field to reinforce your conclusions? Ernesto:                            I think my study is one of the early studies of this field, so getting more studies like this and other channelopathies, getting not just looking at Long QT one through three but looking at all of them, and in patients who've been evaluated at Texas Children's or any other institution would be helpful. And then moving forward to give more credence to the idea that if you have history that's reassuring and physical exam that's reassuring, then you probably don't need to have further testing. Andrew :                           What do you recommend if your index of suspicion is high for Long QT syndrome, so maybe a QTC in the low 480s, maybe a family history of syncope or seizures, do you think whole-exome sequencing is the way to go? Ernesto:                            Right now, that's probably not the best test, given all these incidental findings that we don't really know what to do with. There's other tests that are more high-tailored for those specific diseases, like Long QT syndrome panel among others, that are probably more likely to give you a positive post-test probability. Andrew :                           So testing for the disease you're suspicious for as opposed to testing indiscriminately? Ernesto:                            Yeah. Andrew :                           So Ernesto, thank you so much for taking the time our of your day to speak with us. Ernesto:                            Thank you, Andrew. Andrew :                           I'm here with David Tester, senior research technologist working with Mike Ackerman at Mayo Clinic, and he just gave a wonderful talk on whole-exome sequencing and next-generation sequencing as an unbiased look to determine underlying causes of Sudden Infant Death Syndrome, or SIDS. So David, I'm wondering if you can introduce yourself and talk a little bit about your project. Dave:                                 Sure. I'm Dave Tester and I'm at the Mayo Clinic, again with Mike Ackerman. Dr. Ackerman and I have been together for about 18 years now, with a real focus on genetics of sudden cardiac death disorders. So this latest study was looking at whole-exome sequencing in a population of SIDS cases in collaboration with Dr. Elijah Behr at St. George's University in London.                                            And really the approach, what we were aiming for is really kind of two-fold. First we were looking to determine what is the yield of ultra-rare variance within genes that have been implicated in cardiovascular disorders? These would be the cardiac channelopathies and some of the cardiomyopathies such as ACM or ARVC, for example.                                            And the second thing that we were wanting to look at was can we use this to search for sort of novel candidate genes for Sudden Infant Death Syndrome susceptibility? And so we took that aim and really the main result was to show that about 14% of our SIDS cases had what we term potentially informative variants. And those are going to be variants that were within sort of the major channelopathy genes that are implicated in Long QT syndrome or CPVT as well as loss of function variants within the 90 ICC genes that we had examined.                                            Using the ACMG guidelines for determining the pathogenicity of variants, about 4.3% of our SIDS cases hosted an ACMG guideline predicated likely pathogenic to pathogenic variant. And most of those variants represent either a frame shift or splice site error variance really in minor cardiomyopathy genes and channelopathy genes. So there's still a lot of work that needs to be done in terms of looking at specifically missense variance within channel genes and that sort of thing, and really kind of functionally characterizing those to determine whether or not they truly are pathogenic or if they should remain variants of uncertain significance. Andrew :                           And so you took a very complex disease like SIDS with probably a number of differens ideologies and found a pretty good percentage have suspicious variants, that 14% or so, and then 4% had variants that were so suspicious they would meet American College of Medical Genetics guidelines for being a possible or likely pathologic variant. Where do you think this study lies in sort of the continuum of identifying the genetic ideology of SIDS, and what do you think these findings sort of add to that overall picture? Dave:                                 Well I think these findings in general really just kind of show the complexity of SIDS. Whether or not SIDS is really truly genetic or not, or perhaps it just, if it's not monogenic, perhaps it's polygenic, and so those are some things that we should be considering and looking at. Now some of those questions might be able to be answer through our whole-exome sequencing data set that we have, and I think those are really going to be kind of the next phases.                                            We can also take and do some pathway analyses of the exome sequencing data, for example, and see our variance kind of lining up on certain pathways that may contribute to certain pathologies that could contribute to SIDS. Andrew :                           And in your study, you had a few genes where the number of variants that were found in SIDS cases were higher than in your controls. Can you speak some more about what those genes may tell you in the context of pathway analysis for SIDS? Dave:                                 Yes. So there was ... There were not genes that came out with sort of a genome-wide significance level. But there were at least 400 genes that had a p-value of 0.05 over representation in SIDS versus our ethnic match controls and 17 of those genes have a p-value of 0.005 and we're really kind of focused on some of those that have a little bit higher p-value for us to assess. A few of those genes may represent biologically plausible candidate genes for SIDS and we were kind of actually going through and considering which ones we'd like to follow up on in terms of function. Some of these genes do play a role in, say, cardiorespiratory system and function of the heart as well as in the brain. Andrew :                           So then given all these findings, and the fact that you may have some candidate genes and candidate pathways that might be interesting to look at further, what are the next steps that you think would help this project move forward, and what do you think the field of Sudden Infant Death Syndrome and Sudden Unexplained Death Syndrome needs to kind of move forward? Dave:                                 Well I think from a genetic standpoint, the study that we just complete was really on a large set of unrelated infants that had died suddenly. We did not have access to parental DNA and so moving forward in terms of the genetics, I think incorporating sort of a trio analysis I think would get at the question of sort of [inaudible 00:42:01] variance for example. The other things, in terms of genetic standpoint is perhaps looking at different genetic mechanisms. Whether these are copy number variance that may be missed by exome sequencing, perhaps some of the SIDS could be due to epigenetic abnormalities or even small chromosomal abnormalities that perhaps may not be detected on certain arrays on there being used. So I think going forward, kind of taking those approaches to look for sort of unique genetic variation. Andrew :                           Well Dave, thank you so much for taking the time to speak with me and congratulations on a great project. Dave:                                 All right, great, thank you. Jane Ferguson:  Thanks to Andrew for highlighting the interesting precision medicine research presented at HRS and thanks to you all for listening. We'll be back with more next month.

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Host: Matt Birnholz, MD This Presidential Plenary Scientific Session of the American College of Medical Genetics and Genomics (ACMG) is titled "The Coming Revolution in Medical Genetics: From Double Helix to Genomics and Back Again." Speaking is Dr. Wayne W. Grody, President of the ACMG and Professor in the Departments of Pathology & Laboratory Medicine, Pediatrics, and Human Genetics at the UCLA School of Medicine.

January 2016: Looking back (and forward) on the occasion of ACMG's 25th Anniversary.

August 2016: New Guidelines for Noninvasive Prenatal Screening from the ACMG.

September: Team of experts creates ACMG's first evidence-based clinical guideline recommending exome or genome sequencing for pediatric patients with congenital anomalies or intellectual disability

August: A discussion of ACMG's recent guidance on the integration of genomic information into the EHR.

November 2016: Updating “The List” – The ACMG 56 is now the ACMG 59.

The retina is a thin layer of tissues, cells, and nerves that line the back wall inside the eye.  This layer has millions of light sensing cells that receive and organize visual information according to the Mayo Clinic.On this Ask the Mayo Mom edition of the Q&A podcast, host Dr. Angela Mattke is joined by Dr. Brittni Scruggs, an ophthalmologist at Mayo Clinic Children's Center. Dr. Scruggs is a physician, surgeon, and scientist with a research laboratory at Mayo Clinic studying gene therapy and stem cell therapy for retinal degenerations, including for children. She treats all ages, ranging from newborns to adults. Dr. Scruggs is a member of the national workgroup developing ACMG evidence-based guidelines for diagnosis and clinical management of inherited retinal diseases. Dr. Mattke and Dr. Scruggs explore retinal issues in children and discuss eye safety and health.  Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy