Podcasts about genomic

Featuring an interview with Dr Adrienne G Waks, including the following topics: The Phase III AFT-38 PATINA trial of palbociclib combined with anti-HER2 therapy for hormone receptor (HR)-positive/HER2-positive metastatic breast cancer (mBC) (0:00) Role of immunotherapy in the treatment of breast cancer (8:30) Defining ER-low breast cancer and identifying treatment approaches for this histologic subtype (15:55) Genomic testing approaches for patients with localized breast cancer and identification of candidates for treatment with adjuvant olaparib (19:37) Current role of anthracyclines in the treatment of localized breast cancer (31:17) Available and novel antibody-drug conjugates for the treatment of breast cancer (41:21) Palbociclib with endocrine therapy compared to chemotherapy induction followed by endocrine therapy maintenance for HR-positive, HER2-negative mBC (51:53) CME information and select publications

DSD 6.3 | Big Picture Management Decisions Matter Timeless dairy management decisions, such as voluntary waiting period & days dry, have recently been the topic of interest across the globe. Scrutiny to illuminate the ideal to maximize productive life has left the industry questioning convention.   Michael Overton, DVM at Zoetis worked with co-author Steve Eicker to tease out the answers to these questions from a a massive dataset of 109,000 cows across 60 herds nationwide. This retrospective, observational research project was recently published in the Journal of Dairy Science titled, “Associations between days open and dry period length versus milk production, replacement, and fertility in the subsequent lactation in Holstein dairy cows”. All dairymen should pause to determine the unintended consequences of their management decisions on optimal performance and ultimately the economic success of the herd. Listen in to learn ways to apply concepts from this project to your operation. Topics of discussion 1:33       Introduction of Dr. Overton 2:54       Difference between association vs causation 4:28       Description of data set 4:51       Genomic testing, background 6:31       Advising herds on selection indices DWP$ 10:02     Different measurements collected – carry over impact of days dry and days open 11:50     Figure 4: Impact of previous days open and previous days dry on cumulative milk 14:04     Risk of replacement and impact of mastitis 18:05     How many sins is a dairyman willing to forgive? 19:46    What does your data say for optimal VWP 22:27     Twin events or sex of calf 24:59     Figure 7: Risk of pregnancy   28:46     What do you want Boots on the Ground dairy producers to gain from the project?  Featured Article: Associations between days open and dry period length versus milk production, replacement, and fertility in the subsequent lactation in Holstein dairy cows #2xAg2030; #journalofdairyscience; #openaccess; #MODAIRY; #daysdry; #milk; #previousdaysopen; #VWP; #daysdry; #DWP$; #Zoetis; #dairysciencedigest; #ReaganBluel; 

This week on The Genetics Podcast, Patrick is joined by Dr. John Lepore, physician-scientist and CEO of ProFound Therapeutics. They discuss ProFound Tx's mission to expand the proteome to identify novel drug targets – which resulted in the ProFoundry atlas – and the ways in which John's diverse experiences inform his approach as a leader.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to John02:01 John's background at GSK and his transition to drug discovery05:45 Establishing ProFound Therapeutics to expand the proteome and identify novel drug targets 08:27 Genomic origins of newly-identified proteins and the process of finding them09:49 Developing the ProFoundry atlas and integrating data across assays 15:27 Different approaches to inferring protein links and association to disease17:13 Collaboration with Pfizer to find regulators in the context of obesity18:04 Developing novel antibody-drug conjugates for cancer treatment20:27 Clarifying causality in proteomic data21:59 Approaching novel targets while considering industrial and business factors25:19 John's background as a cardiologist and how that impacts his current work27:26 Tips for biotech companies looking to be noticed by pharma for collaborations30:30 Considerations for investigating new and different therapeutic modalities and techniques33:39 How John consistently reinforces the translational angle as a business leader36:24 Closing remarks and future direction for ProFound TherapeuticsFind out moreProFound Therapeutics (https://www.profoundtx.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Dr. Thomas Chen, Founder, CEO, and CSO of NeOnc Technologies, is working on the challenge of delivering drugs across the blood-brain barrier by using an intranasal delivery approach to target brain cancers. This delivery platform leverages the cranial nerve to transport the drugs directly to the brain, bypassing the blood-brain barrier. Genomic analysis of the long-surviving patients in the phase one trial revealed a common genetic mutation, informing the trial design for the next phase. Thomas explains, "So our platform is what we call intranasal delivery. And with the intranasal delivery, we're not trying to cross the blood-brain barrier. We're trying to cross over it. And how we're doing that is doing the delivery of the drug via what we call the C nerves. Now the cranial nerves are, we have 12 cranial nerves in our brain. These cranial nerves have various functions, but the cranial nerves involved with the nasal brain delivery are the first and the fifth cranial nerves. The first cranial nerve is what we call the olfactory nerve. That's the nerve that's responsible for smell. The fifth cranial nerve is called the trigeminal nerve, which involves facial sensation and allows us to chew."   "So what happens is that when we want to deliver the drug to the brain cancer, we have the patient inhale it. When the patient inhales, it goes through the nose, and through the olfactory nerve, it goes to the brain. Usually, that molecule then absorbs in the spinal brain and then circulates to the target, in this case, brain cancer. Now you know how powerful that cranial nerve is from the standpoint of what it does when you smell something, that scent, that odor gets transported from the olfactory nerve to our brain. And that's basically what we're doing. We're taking something external to the brain, allowing the cranial nerve to absorb and transport it to the brain." #NeOnc #BloodBrainBarrier #BBB #BrainCancer #DrugDelivery neonc.com Download the transcript here

Dr. Thomas Chen, Founder, CEO, and CSO of NeOnc Technologies, is working on the challenge of delivering drugs across the blood-brain barrier by using an intranasal delivery approach to target brain cancers. This delivery platform leverages the cranial nerve to transport the drugs directly to the brain, bypassing the blood-brain barrier. Genomic analysis of the long-surviving patients in the phase one trial revealed a common genetic mutation, informing the trial design for the next phase. Thomas explains, "So our platform is what we call intranasal delivery. And with the intranasal delivery, we're not trying to cross the blood-brain barrier. We're trying to cross over it. And how we're doing that is doing the delivery of the drug via what we call the C nerves. Now the cranial nerves are, we have 12 cranial nerves in our brain. These cranial nerves have various functions, but the cranial nerves involved with the nasal brain delivery are the first and the fifth cranial nerves. The first cranial nerve is what we call the olfactory nerve. That's the nerve that's responsible for smell. The fifth cranial nerve is called the trigeminal nerve, which involves facial sensation and allows us to chew."   "So what happens is that when we want to deliver the drug to the brain cancer, we have the patient inhale it. When the patient inhales, it goes through the nose, and through the olfactory nerve, it goes to the brain. Usually, that molecule then absorbs in the spinal brain and then circulates to the target, in this case, brain cancer. Now you know how powerful that cranial nerve is from the standpoint of what it does when you smell something, that scent, that odor gets transported from the olfactory nerve to our brain. And that's basically what we're doing. We're taking something external to the brain, allowing the cranial nerve to absorb and transport it to the brain." #NeOnc #BloodBrainBarrier #BBB #BrainCancer #DrugDelivery neonc.com Listen to the podcast here

In this episode of the Onc Now Podcast, host Jonathan Sackier is joined by Heather McArthur, Associate Professor in the Department of Medicine at University of Texas, UT Southwestern Medical Center, USA. They discuss recent advancements in breast cancer immunotherapy and the future of personalised care.  Timestamps:    00:00 - Introduction  01:20 - Transformative breakthroughs in immunotherapy  03:51 - Communicating new research to the public  05:48 - Racial disparities in cancer screenings  07:22 - Unmet needs in treating triple-negative breast cancer  11:48 - Genomic profiling and molecular pathways   13:30 - Barriers to personalised treatment plans  15:09 - Designing and conducting large-scale, international trials  19:16 - Optoacoustic imaging in cancer  22:52 - The ‘first' cell and the heterogeneity of breast tumours  25:21 – Heather's three wishes for healthcare 

This episode was originally released on November 14, 2023Sleep is essential to our lives, but our perception of how it functions in our non-waking life is not always well understood. So in the mires of our busy daily lives do we overlook sleep by seeing it as a means of refilling our energy for a productive day? By questioning this assumption, one term rolls from out of the haze: The ‘Circadian Rhythm'.Dr. Kaylee Byers speaks with Dr. Hiroki Ueda from the University of Tokyo in the Faculty of Medicine on demystifying the links between our sleep and genomics. Then neuroscientist Dr. Andrew Coogan shares the connection between sleep and ADHD. Finally, we hear from Dr. Ueda and Dr. Hiroshi Ono, from Hitotsubashi University Business School, on how their homeland of Japan is reckoning with an off-balance relationship with sleep and work.References:Molecular Mechanisms of REM Sleep | NeurosciThe ability to dream may be genetic | Canadian Broadcast Corporation (CBC)Next-Generation Mice Genetics for Circadian Studies | NeuromethodsEvolution of temporal order in living organisms | Journal of Circadian RhythmsLearn about the bunker experiment to understand the human biological clock | BritannicaGenetic sleep deprivation: using sleep mutants to study sleep functions | EMBO reportsCircadian rhythms and attention deficit hyperactivity disorder: The what, the when and the why | Prog Neuropsychopharmacol Biol PsychiatryInsomnia: Definition, Prevalence, Etiology, and Consequences | Journal of Clinical Sleep MedicineNo Sleep for Japan? Survey Reveals Half of Population May Have Insomnia | Nippon.comWhy Sleep Matters: Quantifying the Economic Costs of Insufficient Sleep | Rand CorporationJapan has some of the longest working hours in the world. It's trying to change | CNBCAnnouncement of the establishment of the nonpartisan "Parliamentary League to Promote Initiatives for People's Quality Sleep" | Sleeping Council FederationFounder/Director CTO Yasumi Ueda gave a speech at the inaugural general meeting of the nonpartisan "Parliamentary League to Promote Initiatives for People's Quality Sleep" | ACCELStarsFree-running circadian activity rhythms in free-living beaver (Castor canadensis) | Journal of Comparative PhysiologyCredits:Dr. Rackeb TesdayeCurbing death by overwork | Financial TimesWhy does Japan Work So Hard? | CNBC ExplainsWorked to Death: Japan questions high-pressure corporate culture | France 24 EnglishInside Japan's growing ‘lonely death' clean-up service | CNN InternationalHow can governments help stop overwork? | The Question | CBC News: The National

Thanks to Tim and Mia who suggested one of this week's animals! Further reading: Genomic insights into the evolutionary origin of Myxozoa within Cnidaria A tardigrade, photo taken with an electron microscope because these little guys are incredibly tiny: Show transcript: Welcome to Strange Animals Podcast. I'm your host, Kate Shaw. This week we're going to talk about two microscopic or almost microscopic animals, one suggested by Mia and Tim, the other one I just learned about myself. We'll start with Mia and Tim's suggestion, the water bear, also known as the tardigrade. We've talked about it before but there's always more to learn about an animal. The water bear isn't a bear at all but a tiny eight-legged animal that barely ever grows larger than 1.5 millimeters. Some species are microscopic. There are about 1,300 known species of water bear and they all look pretty similar. It looks for all the world like a plump eight-legged stuffed animal made out of couch upholstery. It uses six of its fat little legs for walking and the hind two to cling to the moss and other plant material where it lives. Each leg has four to eight long hooked claws. It has a tubular mouth that looks a little like a pig's snout. An extremophile is an organism adapted to live in a particular environment that's considered extreme, like undersea volcanic vents or inside rocks deep below the ocean floor. Tardigrades aren't technically extremophiles, but they are incredibly tough. Researchers have found tardigrades in environments such as the gloppy ooze at the bottom of the ocean and the icy peaks of the Himalayas. It can survive massive amounts of radiation, dehydration for up to five years, pressures even more intense than at the bottom of the Mariana Trench, temperatures as low as -450 Fahrenheit, or -270 Celsius, heat up to 300 degrees Fahrenheit, or 150 Celsius, and even outer space. It's survived on Earth for at least half a billion years. Mostly, though, it just lives in moss. Not every tardigrade is able to do everything we just talked about. They're tough, but they're not invulnerable, and different species of tardigrade are good at withstanding different extreme environments. Many species can withstand incredible heat, but only for half an hour or less. Long-term temperature increases, even if only a little warmer than what it's used to, can cause the tardigrade to die. Most species of tardigrade eat plant material or bacteria, but a few eat smaller species of tardigrade. It has no lungs since it just absorbs air directly into its body by gas exchange. It has a teeny brain, teeny eyes, and teeny sensory bristles on its body. Its legs have no joints. Its tubular mouth contains tube-like structures called stylets that are secreted from glands on either side of the mouth. Every time the tardigrade molts its cuticle, or body covering, it loses the stylets too and has to regrow them. In some species, the only time the tardigrade poops is when it molts. The poop is left behind in the molted cuticle. The tardigrade's success is largely due to its ability to suspend its metabolism, during which time the water in its body is replaced with a type of protein that protects its cells from damage. It retracts its legs and rearranges its internal organs so it can curl up into a teeny barrel shape, at which point it's called a tun. It needs a moist environment, and if its environment dries out too much, the water bear will automatically go into this suspended state, called cryptobiosis. Tests in 2007 and 2011 that exposed tardigrades to outer space led to some speculation that tardigrades might actually be from outer space, and that they, or organisms that gave rise to them, might have hitched a ride on a comet or some other heavenly body and ended up on earth. But this isn't actually the case, since genetic studies show that tardigrades fit neatly into what we know of animal development and evolution. In other words,

In this episode, our guests explore the impact of genetic discoveries on inherited retinal dystrophies, in particular retinitis pigmentosa (RP). The discussion highlights a recent study that identified two non-coding genetic variants linked to RP, predominantly in individuals of South Asian and African ancestry. The conversation highlights how advances in whole genome sequencing are uncovering previously hidden causes of genetic disease, improving diagnostic rates, and shaping the future of patient care. It also addresses the challenges faced by individuals from diverse backgrounds in accessing genetic testing, including cultural barriers, awareness gaps, and historical underrepresentation in genomic research. Our host Naimah Callachand is joined by researcher Dr Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, a patient representative diagnosed with retinitis pigmentosa and Founder and Chair of BAME Vision. We also hear from Martin Hills, an individual diagnosed with autosomal dominant retinitis pigmentosa. To access resources mentioned in this episode: Access the Unlock Genetics resource on the Retina UK website Visit the BAME vision website for more information and support Find out more about the groundbreaking discovery of the RNU4-2 genetic variant in the non-coding region which has been linked to neurodevelopmental conditions in our podcast episode   "Discoveries like this lead to better clinical management. We understand better the progression of the disease when we can study this in many individuals from a wide spectrum of ages and different backgrounds. We can provide counselling as Bhavini was talking about. We can provide patients with a better idea of what the future may hold for their eye disease, and potentially, you know, we are all aiming towards being able to develop therapies for particular genes and particular diseases."   You can download the transcript or read it below. Naimah: Welcome to Behind the Genes.   Bhavini: The few common themes that always come out is that people don't really understand what genetic testing and counselling is. They hear the word counselling, and they think it is the therapy that you receive counselling for your mental health or wellbeing. There is already a taboo around the terminology. Then it is lack of understanding and awareness or where to get that information from, and also sometimes in different cultures, if you have been diagnosed with sight loss, you know blindness is one of the worst sensory things that people can be diagnosed with. So, they try and hide it. They try and keep that individual at home because they think they are going to have an outcast in the community, in the wider family, and it would be frowned upon).  Naimah: My name is Naimah Callachand and I am Head of Product Engagement and Growth at Genomics England.  I am also one of the hosts of Behind the Genes. On today's episode I am joined by Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, patient representative.  Today we will be discussing findings from a recently published study in the American Society of Human Genetics Journal which identified two non-coding variants as a cause of retinal dystrophy in people commonly of South Asian and African ancestry. If you enjoy today's episode, we'd love your support. Please like, share, and rate us on wherever you listen to your podcasts.  Okay, so first of all I would like to ask each of the three of you to introduce yourselves. Bhavini, maybe we'll start with you.  Bhavini: Hi, I'm Bhavini Makwana, patient representative, and also Chair of BAME Vision. I have other roles where I volunteer for Retina UK, and I work for Thomas Pocklington Trust.  Naimah: Thanks Bhavini. Gavin.  Gavin: Hi, my name is Gavin Arno, I am Associate Director for Research at the Greenwood Genetic Centre in South Carolina, and I am Honorary Associate Professor at the UCL Institute of Ophthalmology in London.  Naimah: Thanks Gavin. And Kate.   Kate: Hi, I'm Kate Arkell, Research Development Manager at Retina UK.   Naimah: Lovely to have you all today. So, let's get into the conversation then. So Gavin, let's come to you first. First of all, what is retinitis pigmentosa and what does it mean to have an inherited retinal dystrophy?  Gavin: So, retinitis pigmentosa is a disorder that affects the retina at the back of the eye. It is a disease that starts in the rod photoreceptor cells. So, these cells are dysfunctional and then degenerate causing loss of peripheral and night vision initially, and that progresses to include central vision and often patients will go completely blind with this disease. So, retinal dystrophies are diseases that affect the retina. There are over 300 genes known to cause retail dystrophy so far, and these affect different cells at the back of the eye, like retinitis pigmentosa that affects the rods. There are cone rod dystrophies, ones that start in the cone photoreceptors, macular dystrophies that start in the central retina, and other types of retinal dystrophies as well.  Naimah: Thanks Gavin. And Bhavini, just to come next to you. So, you received a diagnosis of retinitis pigmentosa at the age of 17 after a genetic change was found in the RP26 CERKL gene. At this time only ten other families in the UK had been identified with this type of genetic alteration. Would you mind sharing a bit more about your journey to your diagnosis?  Bhavini: Yeah. So, at the age of 17 is when I got officially diagnosed with retinitis pigmentosa, but leading up to that I was experiencing symptoms such as night blindness. So, I struggled really badly to see in the dark, or just in dim lighting, like this time of the year in winter when it gets dark quite easily, all my friends from college could easily walk across the pavement, but I struggled. I was bumping into a lot of things. Like things that I wouldn't really see now that I know my peripheral vision, I was losing that, so like lamp posts or trees or bollards, I would completely miss or bump into them. I was missing steps, and had a really, really bad gaze to the sun. Like, everything was really hazy. That continued and I just put it down to stress of exams. You know, just given that age and where I was at the time of my life. But then it kind of continued. So, I went to the see the optician who then referred me, and after months of testing I got diagnosed with retinitis pigmentosa. Back in the late 90s when I was diagnosed there wasn't really anything about genetic testing, or cures., or treatments. I was basically just told to get on with it, and that was it.   It was only until about 15/16 years later I came across Retina UK, started understanding what retinitis pigmentosa is, and what it means, and then when I was offered genetic testing and counselling at one of my annual Moorfields appointments, they explained to me what it involved, what it could mean, what kind of answers I would get, and I agreed to take part. It was a simple blood test that myself and both my parents took part in.      Naimah: Thanks for sharing that Bhavini. So, I know you were able to receive a diagnosis through whole genome sequencing in the 100,000 Genomes Project after the alteration in the gene was found, and this was found in the coding region of the genome. But in this study that we are talking about in this podcast, we know that the two genetic changes that were found, they were in the non-coding region of the genome. Gavin, could you tell me in simple terms what the difference is between the coding and non-coding region of the genomes and why these findings are significant in this case?   Gavin: Yes, sure. So, the human genome is made up of about 3 billion letters or nucleotides which are the instructions for life essentially. Now, within that human genome there are the instructions for roughly 20,000-25,000 proteins. This is what we call the coding genome. These are the bits of DNA that directly give the instructions to make a protein. Now, we know that that part of the genome is only roughly 2% of the entire genome, and the remaining 98% is called the non-coding genome. Now, we understand that far less well. We have a far poorer understanding of what the function of the non-coding genome is versus the coding genome. So, typically molecular diagnostic testing or genetic testing is focused on the coding genome, and historically that has been the fact. Now with advances in genome technologies like whole genome sequencing and the 100,000 Genomes Project, we are able to start to look at the non-coding genome and tease out the previously poorly understood causes of genetic diseases that may lie within those regions of the genes.   Naimah: Thanks Gavin, I think you have just really highlighted the possibilities available with looking at the non-coding region of the genome.  Kate, coming to you next. I wanted to talk about the importance of uncovering and understanding genetic causes of inherited retinal dystrophies, and how do discoveries like these change the landscape of care for patients with inherited retinal dystrophies?  Kate: So, getting a genetic diagnosis can really help families affected by inherited retinal dystrophy. It helps them and their ophthalmologists to better understand their condition, and in some cases gain some insight into possible prognosis, which helps people feel a lot more in control. It can also potentially inform family planning decisions and even open up options around access to reproductive technologies for example, not only for the individual, but sometimes also for their close relatives. Of course, researchers are making great strides towards therapies, some of which have reached clinical trials. But a lot of these approaches are gene specific, so for people who know their genetic diagnosis, they are more able to recognise research that is most relevant to them and quickly pick out potential opportunities to take part. At the moment it is still the case that around 30% of our community who have a genetic test will not receive a clear result, and that can feel very frustrating. So, the more discoveries like this that are made, the better.   Naimah: Thanks Kate.  So, now we are going to hear a clip from Martin Hills, our Retina UK patient representative who has been diagnosed with autosomal dominant retinitis pigmentosa. Martin has undergone genetic testing and shares more about his experience.  Martin: My name is Martin Hills, and I was officially diagnosed with autosomal dominant retinitis pigmentosa in 2001, and because of that I immediately had to stop driving which made a huge impact both on myself and my family.  My eyesight has slowly deteriorated over the years. It first started with difficulty seeing at night, and also playing some types of sport, which I think probably was in my 20s. My peripheral vision has been lost slowly and now has completely gone. Fortunately, I still have some reasonable central vision left which is a great help. I am registered as severely sight impaired, and I am also a symbol cane user. My father and aunt were both diagnosed with this condition, and my daughter has been relatively recently, as has altogether eight members of our wider family, and that also includes two younger generations. In 2015 I went for genetic counselling and testing and at that time it was for 176 genes known to be associated with retinal dystrophies. I believe that has now gone up to about 300, but at the time they couldn't recognise what my faulty gene was, and that has still been the case to my knowledge to date.   I have also been part of the 100,000 Genome Project along with several others of my wider family, and I am also a participant in the UK Inherited Retinal Dystrophy Consortium RP Genome Project, which has been sponsored by Retina UK. The impact of not having a positive genetic test result is quite interesting and has really been a rollercoaster. I guess it is all about hope, and to start with when I knew I was going to be genetically tested, I think my first reaction was optimism, and I think if you have a positive test result, that is a real hope for the future. I think that is quite exciting particularly as things seem to be progressing so rapidly. But because I didn't get a positive result, the next reaction I had really was disappointment because I felt one step behind people with a positive result. Of course the natural reactions are one of frustration, and then I guess followed by realisation of the situation, and heading towards trying to adjust and making coping strategies for the future.  I still feel that genetic testing for all forms of medical conditions is so important and has a huge future in understanding and then potential treatments for so many medical issues. I guess it might be a bit too late for me, but if I can contribute to finding a restorative treatment for the younger generations of my family, and for that matter other people, then I think that is good enough for me.   Naimah: So, we have just heard from Martin that although he has not been able to have a positive genetic test result, his involvement in various studies may have benefits in helping others find treatment. So, I guess on that point Bhavini, maybe you could comment, or ask you how you felt whenever you were about to get a diagnosis through whole genome sequencing?  Bhavini: Yes. When I got called in almost three and a half years after the testing that took place was a massive, massive relief because not only did I get genetic counselling before the testing period, but I got called in and I spoke to a genetic counsellor who explained what they had been able to find and what kind of RP it was, how it would progress, and just answer so many questions. I am the mother of two daughters and even having two children, I lost a lot of sight after my first daughter, but at that time there wasn't any evidence or there wasn't any … you know, there was nothing I even knew about what questions to ask or anything, so I did go on to have a second child and drastically lost more sight. I had always been told, because the lack of awareness and understanding of RP in my family, and I am one of four children, and I am the only one that has it, so there is no other family history. Now I know it could have skipped generations, but I was always told things like it was karma. I must have done something in my past life. I was told to kind of have these herbs or these remedies to cure my sight loss, you know my RP. I was even desperate enough to kind of …  all these bogues treatments that you find online. You know, anything. I was so desperate to find anything that would help me.   When I received that testing and the counselling, it explained so much about how my daughters may or may not be affected, how they are carriers, and that was explained to me, how it would progress. So many questions and worries that I had for almost a decade and a half, they were answered. And not only for me, for my family, and all those people that told me all these sorts of things that I used to worry about that could have caused my RP. I was able to explain it to them and they understood that it was nothing to do with me being bad in my past life. It was actually you know, there is something scientific about it. So, it kind of gave me lots and lots of answers, and actually I then created a private Facebook page just with my RP26 CERKL genetic that I have been diagnosed with, just to see if there is anybody else out there, because when I was diagnosed, I think at the time I was told there was only myself and nine other families in the UK diagnosed with this particular gene. Now, I haven't been that active on it, but you know there are people across the world who found my post and joined the group, and we share experiences about the age that we were kind of diagnosed, the kind of rate the symptoms have developed. It is so fascinating because we have got such similar experiences.   There is parents on there who are there on behalf of their children, and it is just so nice to see … I know it is RP, but the specific gene and the rate of which we have experienced all the symptoms, it is quite similar. So, it has been quite supportive and helpful and reassuring to my family including my daughters.  Naimah: That's incredible Bhavini and it's really nice that you have created that group and created kind of like a support network for all the other families that have been affected by the same genetic condition as well. Yeah, that's incredible. Gavin, I know the findings in the study show that the genetic changes in this study are more common in people of African and South Asian ancestry. So, so I want to understand why is this an impactful finding in the study?  Gavin: Yes, so Kate mentioned that around 30% of people with inherited retinal dystrophies who have genetic testing don't get a molecular diagnosis and we are working in my research lab and many other research labs to improve that. Now, that figure is very much higher in patients of for example African ancestry in the UK, and this is partly due to the fact that historically and even now genetic studies have been focused on European individuals and taken place in the US, and the UK, and Europe, and wealthy countries across the world. This means that people of African ancestry are poorly represented in genetic studies, not just genetic studies of genetic disease, but population studies as well. So, we have less of an understanding of the genetic variants found in the genomes of individuals of African ancestry. So, that means we solve less of the genetic cases, particularly at Moorfields we published a paper on this several years ago with the diagnostic rates in European patients versus those of African ancestry, and it was very, very much lower. So, we need to do better for those patients, and this study identified a cause of retinitis pigmentosa in 18 families of African ancestry who were recruited to the 100,000 Genomes Project.   This is a fairly large proportion of the patients with RP of African ancestry seen at Moorfields Eye Hospital, and when we contacted collaborators around the world many more families were identified, and I think we ended up publishing around about 40 families who were affected by this particular mutation. So, we can look at that variant, we can look at the DNA sequence around that variant, and we found there is a chunk of DNA around the mutation in the gene that was coinherited by all of those different individuals. So, this is what we call an ancestral haplotype. It's an ancient variant that goes back many, many generations and it has a fairly high carrier frequency in genomes of African ancestry. So, we think this will be a fairly significant cause of retinitis pigmentosa across the continent of Africa. And so, identifying it will enable us to provide a molecular diagnosis for those families. Potentially there will be many more families out there who don't know they have this cause of disease yet. They may be affected but they haven't yet received genetic testing.   But discoveries like this lead to better clinical management. We understand better the progression of the disease when we can study this in many individuals from a wide spectrum of ages and different backgrounds. We can provide counselling as Bhavini was talking about. We can provide patients with a better idea of what the future may hold for their eye disease, and potentially you know we are all aiming towards being able to develop therapies for particular genes and particular diseases. As Kate mentioned many of the gene therapies are gene specific, so if we identify a cause of disease that is predominant like this and affects many, many people, then of course there is more interest from the pharmaceutical industry to develop a therapy for that specific gene.  Naimah: Thanks Gavin. I think that really does showcase how impactful these findings really are. Kate, can I come to you. So, Gavin touched on it there that people with African and Asian ancestry are significantly less likely to get diagnosed, but why is it important to ensure that these groups are represented in the genomic datasets?  Kate: So, we need to ensure that genetic testing and diagnostic accuracy works for everyone, and not just those of European ancestry. So, as Gavin said if the datasets don't reflect the genetic variations seen in African or Asian populations, then the tests based on those data are more likely to give incomplete results for those groups of people. We really need a diverse range of genetic information for researchers to work on. As it is clear from this study's results, populations from African backgrounds for example may have unique genetic mutations linked to retinal dystrophy. So, if those are really underrepresented in datasets based on European populations, that is obviously going to present a problem. Gavin mentioned access to treatment. We need to overcome some of these disparities in healthcare access, and   inclusion of broad spectrum of genetic data is actually a foundation for that.   Naimah: Thanks Kate.  So underrepresented groups are often less likely to know about genetic testing due to a combination of social economic and systemic factors that create barriers to access information. Cultural taboos can also play a significant role in shaping attitudes towards genetic testing, and I think Bhavini you kind of touched on this slightly with some of your experiences. I wonder, did you experience any of these cultural taboos?  Bhavini: Yes, some of them, but I think by the time I was informed about what genetic testing and counselling is I had come across Retina UK and I had already started having that background knowledge, so when that was offered to me, I actually had a basic understanding. But as Chair of BAME Vision I work with a lot of ethnic communities, and when I speak about my own personal experience about receiving genetic testing and counselling, I kind of break it down into my own language, and the few common themes that always come out is people don't really understand what genetic testing and counselling is. They hear the word counselling, and they think it is the therapy that you receive counselling for your mental health or wellbeing.  So, again there is already a taboo around the terminology. Then it is lack of understanding and awareness, or where to get that information from. Also sometimes in different cultures, if you have been diagnosed with sight loss, you know blindness is one of the worst sensory things that people can be diagnosed with, so they try and hide it. They try and keep that individual at home, because they think they are going to have an outcaste in the community and the wider family, and you will be frowned upon, people will talk really bad.   So, it is not really common knowledge, so they don't even talk about it. So, there is a lot of layers to unpick there. That is one of the priority areas in 2025 that we at BAME Vision are going to be working on to try and raise that awareness in different communities about what genetic testing is, what it could mean, how to get genetic testing if it is not offered to you at your own clinic. There is a lot of work I know Retina UK have done, so working with them, and how we can reach different communities to raise that awareness.  Naimah: That's great. You have touched on how important the education piece is. I wonder, do you have any other examples of how healthcare providers and genetic counsellors might better engage communities to ensure that they are receiving the care that they need?  Bhavini: Yeah, absolutely. So, I think having information in different languages is essential, and I don't expect to have lots and lots of leaflets in different languages. Whether it is audio form or whether there is different professionals within that setting that speak different languages that can communicate to those patients, or even their family or friends that could translate. I think language is definitely something. And having representation, so like different people who have accessed this and sharing their story and going out into community groups and sort of sharing those messages, is definitely what has been working for us, and we have been doing that on other topics that we have used.  Naimah: Yes, they all sound like really important ways to try and engage with different communities. You have already mentioned how amazing that Retina UK have been and the support that you have received from them. So, I wonder Kate, if you could tell us a bit more about the support that is available for those with inherited sight loss, and how these resources can support people from underrepresented groups as well.  Kate: So, we have a range of support services at Retina UK most of which involve our fantastic team of volunteers, one of whom is Bhavini, who are all personally affected by inherited retinal dystrophy themselves. So, they are all experts by experience so to speak. The team also does include members of the Asian community as well. So, if somebody makes a call to our helpline, they will be able to speak to somebody who genuinely understands what they are going through, which can be a lifeline for those who are feeling isolated and especially I think as Bhavini mentioned, if they feel unable to talk openly with their own family and certainly within their community. We have a talk and support service that offers ongoing more regular telephone support as well as in-person and online peer support groups where people can make social connections with others in similar situations. I think Bhavini has mentioned that she herself runs our London and Southeast local group.  We also have an information resource called Unlock Genetics. That explains genetics in understandable language and clearly explains how people can access testing and what that will involve. So, we have stories on there from people who have gone through the process and talk about that. So, that is available on our website, and we can provide it in audio format as well.  Naimah: So Gavin, looking to the future, what does this research mean for patients with sight loss and their families? What does this mean in the future?  Gavin: So, I think now that we have access to whole genome sequencing through projects like the 100,000 Genomes Project, we are able to start the process of understanding new causes of disease that are found outside of the coded region.  So, we can now look for non-coding variants that cause disease which was previously not possible because genetic testing was focused on 2% of the genome. As we make discoveries like this these will inform future studies. So, the more we identify this type of variant and are able to functionally test the effect on the gene or the protein, we are able to use that information to lead future tests. What this needs is large population datasets to be able to analyse these sorts of variants at scale. The more genomes we have the better our understanding will be of our population frequencies, and the key thing is here for inherited retinal dystrophies, all of these variants that we are identifying are very, very rare. So, we only find them in a very small number of individuals affected with disease, and an infinitely smaller number of individuals in the unaffected general population. So, the larger that population dataset is that we can study, the better we can understand the rarity of these variants and pick those out from the many, many millions of non-pathogenic or harmless variants that we find in the genomes of all the individuals.  Naimah: Do you think the paper will help lead the way for diagnosis of other conditions in African and South Asian communities?    Gavin: Yes. The better we understand causes like this, and we are now at the point where most of the genes that cause retinal dystrophy have been identified already, so the remaining causes to be identified will be these more difficult to find cases, non-coding variants, structural variants, which we haven't touched on today which are larger rearrangements of the genome. These things are harder to find, harder to interpret, so the more that we find like this, the better our ability will be to interpret those sorts of variants. There are many similar findings coming out of genome studies like 100,000 Genomes Project. For example, there was a significant finding recently published on a non-coding RNU gene which causes a significant proportion of neurological disorders in the 100,000 Genomes Project. You need these studies to be able to drive forward the research in areas like this.   Naimah: Thanks Gavin, and the discovery that you are mentioning is the RNU4-2 gene that was discovered earlier this year. You can hear more about that on our other podcast on our website which is ‘How has groundbreaking genome work discovery impacted thousands far and wide' to learn more about that as well. But yeah, I agree it is another really great example of how impactful these findings can be. Okay, we'll wrap up there. Thank you to our guests Gavin Arno, Kate Arkell, and Bhavini Makwana for joining me today as we discussed the findings from a recent study which has identified genetic changes responsible for retinal dystrophy, and people commonly of South Asian and African ancestry. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin of Ventoux Digital.

About this episode: Since the mapping of the human genome in 2003, scientists have sought data from Indigenous and isolated populations. But often that research doesn't translate into better health care for the groups whose biological specimens informed it. In this episode: all about the Native Biodata Consortium, a research organization that collects, stores, and shares data from indigenous environments and communities. Guest: Joseph Yracheta, Pūrepecha, is a biomedical researcher and the executive director of the Native Biodata Consortium. Host: Dr. Josh Sharfstein is vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, a faculty member in health policy, a pediatrician, and former secretary of Maryland's Health Department. Show links and related content: Rapid Acceleration of Diagnostics (RADx)—The National Institutes of Health Native Americans Graves Protection and Repatriation Act—National Park Service Tribal Data Repository—Data for Indigenous Innovations, Interventions and Implementations Contact us: Have a question about something you heard? Looking for a transcript? Want to suggest a topic or guest? Contact us via email or visit our website. Follow us: @‌PublicHealthPod on Bluesky @‌JohnsHopkinsSPH on Instagram @‌JohnsHopkinsSPH on Facebook @‌PublicHealthOnCall on YouTube Here's our RSS feed

1/2: #BIOWEAPON. PRC suspect of weaponizing genomic research/technology acquired from America. Craig Singleton, FDD. 1940

2/2: #BIOWEAPON. PRC suspect of weaponizing genomic research/technology acquired from America. Craig Singleton, FDD. 1961

Preview: Colleague Craig Singleton (FDD) on Xi Jinping's Ambition to Harness Genomic Research for Potential PLA Weaponization. More Tonight. 1930

  Three years ago David Mittelman came on Unsupervised Learning to talk about emerging possibilities on the frontiers of genomics, and his new startup at the time, Othram. Since then, Othram's work has been featured widely in the media, including in a Law & Order episode, and the firm has solved thousands of unsolved cases, with nearly 500 public. For over a decade, Mittelman has been at the forefront of private-sector genomics research. He trained at Baylor College of Medicine and was previously faculty at Virginia Tech. Razib and Mittelman discuss the changes that the rapid pace of genomic technology has driven in the field of genetics, from the days a $3 billion dollar draft human genome in the year 2000 to readily available $200 consumer genomes in 2024. One consequence of this change has been genetics' transformation into information science, and the dual necessities of increased data storage and more powerful, incisive data analysis. Genomics made information acquisition and analysis so easy across the research community that it allowed for the pooling of results and discoveries in big databases. This has pulled genetics out of the basic science lab and allowed it to expand into an enterprise with a consumer dimension. Mittelman also discusses the improvements and advances in DNA extraction and analysis techniques that allow companies like his to now glean insights from decades-old samples, with bench sciences operating synergistically with computational biology. Razib and Mittelman talk about how he has helped solve hundreds of cold cases with new technology, in particular, at the intersection between new forensic techniques and both whole-genome sequencing and public genetic databases. They also discuss the future of genetics, and how it might touch our lives through healthcare and other domains, passing from inference to fields like genetic engineering  

BUFFALO, NY - January 22, 2025 – A new #review was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms." Researchers Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala, and Andrew A. Davis from the University of Missouri-KC School of Medicine and Washington University in St. Louis School of Medicine explore HER2-low breast cancer, a recently recognized type of breast cancer that is changing the way clinicians should approach treatment. The review explains what makes HER2-low breast cancer different and highlights new treatment options that are helping patients. “Breast cancer, which has been historically classified as HER2-positive versus HER2-negative, is currently facing a paradigm shift in both the definition of HER2 status and in the existing treatment algorithms.” Breast cancer is usually classified into two main types based on the HER2 protein: HER2-positive or HER2-negative. HER2-low breast cancer falls somewhere in between. Thanks to new targeted treatments, such as a drug called trastuzumab deruxtecan, patients with HER2-low breast cancer now have more options and better chances of responding to treatment. The review looks at recent studies on the genetics of HER2-low breast cancer. Researchers found that these tumors are often hormone receptor (HR)-positive, meaning they respond to hormones like estrogen. Some tumors also carry a common genetic change called a PIK3CA mutation, which could affect how well treatments work. However, experts say HER2-low breast cancer is not a completely separate breast cancer type but rather an opportunity for more personalized treatment. “Despite evidence from existing literature that HER2-low breast cancer does not represent a distinct biologic and prognostic subtype, the introduction of HER2-low expression as a therapeutic target has expanded patient eligibility for a potent class of anti-HER2 drugs, HER2-directed ADCs, with potential for significant efficacy.” Despite these advances, diagnosing HER2-low breast cancer can still be difficult. Current testing methods are not always accurate, and different laboratories may get different results. The review calls for better detection methods to make sure patients who can benefit from these new treatments are correctly identified. With cancer treatments becoming more personalized, the review also explains how clinicians can fit HER2-low treatments into existing guidelines to help patients. The success of targeted therapies is changing how breast cancer is treated, especially for patients whose cancer has metastasized. In conclusion, experts believe ongoing research will continue to improve the way HER2-low breast cancer is diagnosed and treated. However, they stress the need for better detection methods and continued exploration of new therapies to help patients get the best possible care. DOI - https://doi.org/10.18632/oncotarget.28680 Correspondence to - Andrew A. Davis - aadavis@wustl.edu About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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We're thrilled to share a special episode drop from one of our producers, Kira Dineen, and her flagship podcast, DNA Today! As a multi award winning genetics podcast with over 12 years of groundbreaking episodes, DNA Today explores the latest in genetics and genomics through expert interviews and engaging discussions.    To celebrate the new year, this episode reflects back on the top genetics and genomics news stories during 2024. The top stories we chatted about are from the American Journal of Human Genetics' “Genomic medicine year in review: 2024” paper.    Joining Kira Dineen for this discussion are two leaders in genomics: Dr. Bruce Gelb and Dr. Eric Green. In this reflective conversation, Kira Dineen, Dr. Bruce Gelb, and Dr. Eric Green discusses the significant developments in genetics and genomics over the past year, including the recent American Society of Human Genetics (ASHG) conference. They explore themes such as variable expressivity, the integration of genomics in human genetics, and the importance of diversity in genomic research.    The discussion also highlights key publications in genomic medicine and the evolving landscape of genetic research, emphasizing the need for continued focus on prevention and the implications of polygenic risk scores. They converse about the evolving landscape of genomic medicine, highlighting key advancements in research, particularly in areas like hemochromatosis and CRISPR technology. They reflect on the rapid progress made in genomic sequencing, especially in newborns, and the transformative impact it has on healthcare, particularly in NICUs. The discussion emphasizes the importance of diverse studies and scalable solutions in genetic counseling, as well as the future potential of genomic medicine to save lives and improve health outcomes.    Top 2024 Genomic Medicine Advancements Testing and managing iron overload after genetic screening-identified hemochromatosis Actionable genotypes and their association with lifespan in Iceland Impact of digitally enhanced genetic results disclosure in diverse families Chronic disease polygenic risk scores for clinical implementation in diverse US populations Skeletal Muscle Ryanodine Receptor 1 Variants and Malignant Hyperthermia Treating inherited retinal disease with gene-editing Validation of a clinical breast cancer risk assessment tool for all ancestries Broader access to clinical genome sequencing benefits diverse individuals with rare diseases Benefits for children with suspected cancer from routine whole-genome sequencing Clinical signatures of genetic epilepsies precede diagnosis in electronic medical records   The Guests:    Bruce D. Gelb, M.D. is the Director and Gogel Family Professor of the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai. He is Professor of Pediatrics and of Genetics and Genomic Sciences. Dr. Gelb completed a pediatric residency and pediatric cardiology fellowship at Babies Hospital of Columbia-Presbyterian Medical Center and Texas Children's Hospital at the Baylor College of Medicine, respectively. He joined the faculty at Mount Sinai in 1991 after fellowship and has remained there since. He developed and now oversees an extensive program in genomics/gene discovery for congenital heart disease. Dr. Gelb has received the E. Mead Johnson Award from the Society for Pediatric Research and the Norman J. Siegel New Member Outstanding Science Award from the American Pediatric Society. He was elected to the American Society of Clinical Investigation and the National Academy of Medicine (formerly, the Institute of Medicine). Dr. Gelb is the President for the American Pediatric Society, Immediate Past President for the International Pediatric Research Foundation and Treasurer-Elect for the American Society of Human Genetics. In addition to his research, he co-directs the Cardiovascular Genetics Program at Mount Sinai.   Dr. Eric Green is the director of the National Human Genome Research Institute (NHGRI) at the U.S. National Institutes of Health (NIH). As NHGRI director, Dr. Green leads the Institute's research programs and other initiatives. He has played an instrumental leadership role in developing many high-profile efforts relevant to genomics. Dr. Green received his B.S. degree in bacteriology from the University of Wisconsin - Madison in 1981, and his M.D. and Ph.D. degrees from Washington University in 1987. Coincidentally, 1987 was the same year that the word “genomics” was coined. Dr. Green's relationship with the Institute began long before his appointment as director. He served as the Institute's scientific director (2002 - 2009), chief of the NHGRI Genome Technology Branch (1996 - 2009) and founding director of the NIH Intramural Sequencing Center (1997 - 2009). Prior to that, he played an integral role in the Human Genome Project. Dr. Green is a founding editor of the journal Genome Research (1995 - present) and a series editor of Genome Analysis: A Laboratory Manual (1994 - 1998), both published by Cold Spring Harbor Laboratory Press. He is also co-editor of Annual Review of Genomics and Human Genetics (since 2005). Throughout his career, he has authored and co-authored over 385 scientific publications.    Dr. Green is a recurring guest on DNA Today, and he might hold the title as the guest who has been on the show the most times! He was featured on Episode #182 when we chatted about the Human Genome Project and the recent completion of the human genome sequence -- from telomere to telomere. Dr. Green was a panelist on the PhenoTips Speaker Series installment that our host Kira Dineen moderated about population genomics in clinical practice, this was also released on the DNA Today podcast feed as Episode #260. He was also on the last couple years for our genetics wrapped 2022 (#214) and 2023 (#263).    Be sure to subscribe to DNA Today wherever you get your podcasts to explore hundreds of episodes on topics ranging from genetic counseling to cutting-edge research in genomics. New episodes are released every Friday. In the meantime, you can binge over 300 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, this includes some episodes recorded at NBC Universal Stamford Studios.    DNA Today is hosted and produced by Kira Dineen. Our video lead is Amanda Andreoli. Our social media lead is Kajal Patel. Our Outreach Intern is Liv Davidson. And our logo Graphic Designer is Ashlyn Enokian, MS, CGC.    See what else we are up to on Instagram, X (Twitter), Threads, LinkedIn, Facebook, YouTube and our website, DNAToday.com. Questions/inquiries can be sent to info@DNAtoday.com. 

In this episode of The ASHE Podcast, we explore how innovative approaches in infection prevention are reshaping healthcare practices. Guests Graham Snyder, Elise Martin, and Ashley Ayers join the discussion to discuss their study titled "Impact of Discontinuation of Contact Precautions on Surveillance- and Whole Genome Sequencing-Defined Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections" and what it means for the future of infection control. The conversation explores the evolving role of contact precautions (CP) in managing MRSA transmission. The discontinuation of CP has sparked debates in infection prevention, with this study providing a fresh perspective through whole genome sequencing (WGS). Unlike traditional surveillance methods, WGS offers deeper insights into MRSA transmission dynamics, unveiling patterns that can redefine how we approach infection control in acute care settings. The study's findings revealed a surprising drop in MRSA healthcare-associated infections (HAIs) post-discontinuation of CP, raising questions about how to balance infection prevention with resource management and patient safety. By reducing reliance on CP, hospitals may gain advantages such as cost savings and fewer adverse effects for patients, without compromising care quality. Finally, the episode delves into challenges faced during the study and the need for further research to refine infection prevention strategies. Future efforts could focus on tailoring CP to specific risks and developing more precise methods for tracking and preventing MRSA transmission. Be sure to read the full article available at Cambridge.org/ASHE. And for the official SHEA recommendations for MRSA treatment and prevention visit: https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/sheaidsaapic-practice-recommendation-strategies-to-prevent-methicillinresistant-staphylococcus-aureus-transmission-and-infection-in-acutecare-hospitals-2022-update/5DB835D2E13F7E813A8A2FD7CB8386BD

In this week's episode we'll learn more about how clonal hematopoiesis affects prognosis in patients with telomere biology disorders, consider recently uncovered molecular subtypes of extracutaneous juvenile xanthogranulomas, and discuss a clinical trial of the BCMA-CD3 bispecific antibody teclistamab in patients with relapsed/refractory multiple myeloma who have received previous BCMA-targeted therapy.Featured Articles:Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutationsRecurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissueEfficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies

In a conversation with CancerNetwork® during Pancreatic Cancer Awareness Month, Tanios S. Bekaii-Saab, MD, spoke about various developments in the pancreatic cancer treatment field. Throughout the discussion, Bekaii-Saab weighed the benefits of currently available chemotherapeutic regimens for patients with metastatic disease, discussed research on the potential for precision medicine in those with KRAS wildtype pancreatic ductal adenocarcinoma (PDAC), and detailed ongoing initiatives to improve outcomes among those with RAS mutations and other targetable genomic alterations. Bekaii-Saab is the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research, chair and consultant in the Division of Hematology and Medical Oncology at Mayo Clinic in Arizona, and co-leader of Advanced Clinical and Translational Science at Mayo Clinic Cancer Center. Given the prevalence of RAS mutations and other alterations in patients with pancreatic cancer, Bekaii-Saab especially emphasized the use of genomic analysis to inform personalized treatment decision-making in the field. Screening patients to detect aberrations such as microsatellite instability-high tumors, BRAF 600E mutations, KRAS G12C mutations, and NRG1 fusions can open the door for the development and use of targeted agents, which may consequently improve patient outcomes.  Looking ahead, Bekaii-Saab noted the need to adapt the therapies that have shown activity in the later stages of the disease to earlier treatment settings. Although “great work” has been achieved with chemotherapy and surgical techniques, he highlighted the importance of bringing targeted agents to earlier lines of therapy to further increase the likelihood of positive outcomes for patients.  “I have never been more optimistic. I'm always the eternal optimist, but I'm even more optimistic today that we're going to move the needle for our patients with pancreatic cancer and continue to enhance that likelihood of living longer, having a better quality of life, or even increasing the level of a cure for this cancer,” Bekaii-Sabb stated. “Certainly, the future looks bright. We're chipping away, one drug at a time. We can now remove that whole concept of nihilism in pancreatic cancer and look quite optimistically on the future.”

Paul Wheatley-Price, BSc, MBChB, MD, FRCP (UK) / Parneet K. Cheema, MD - Addressing Key Challenges to Improve Outcomes in Patients With NSCLC With Rare Actionable Genomic Alterations

In this explainer episode, we've asked Adrianto Wirawan, Director of Bioinformatics Engineering at Genomics England, to explain what the term 'no primary findings' means. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you've got any questions, or have any other topics you'd like us to explain, feel free to contact us on info@genomicsengland.co.uk. You can download the transcript or read it below. Florence: What does ‘no primary findings' mean? I'm joined by Adrianto Wirawan, Director of Bioinformatics Engineering for Genomics England, to find out more. So firstly, Adrianto, when we speak about findings from genomic tests, what does this mean? What are we looking for when we do a genomic test?  Adrianto: Our DNA is made up of a long sequence of letters that act like instructions for your body.  Genomic testing analyses these letters to see if there are any unusual patterns or changes that might change your health. You can imagine your DNA as a book full of recipes for your body. Every recipe tells your body how to make proteins that keep you healthy, and sometimes there might be a typo in the recipe, like missing an ingredient or mixing up the steps. This could result in a health problem, just like how a changed recipe can lead to a bad dish.  On average, we would expect about 5 million out of our 3 billion DNA letters to be different. And each of these, we call them a genetic variant. Genomic testing is designed to examine some of these variants to help inform our healthcare. So, for example, in understanding why certain health problems happen and in choosing the best treatment based on our unique genetic makeup.  Florence: And what do we mean by primary findings?  Adrianto: Primary findings mean that in a patient's genomic testing, we identified a set of variants that is linked to the patient's condition. The variants that we have makes us who we are. However, not all of them cause a disease or contribute to a health problem. our bioinformatics pipelines will automatically prioritise variants of potential relevance to the patient's conditions. Using this data, the NHS clinical scientists will then determine whether any of these prioritised variants are linked to the patient's condition and whether a genetic diagnosis has been identified, which would explain why certain health problems happen.  Florence: So, then what happens when there are no primary findings?   Adrianto: When no primary findings are found, that means that no genetic diagnosis has been identified. As developments are made and our knowledge of the variance improves over time, additional findings might be identified in the future.  The clinical team responsible for a patient's care may request reanalysis of data according to the national guidance, following a change in the patient's clinical status to inform reproductive decisions, or after significant new disease gene associations have emerged.  In addition, Genomics England also provides the diagnostic discovery pathway where we focus on uncovering new diagnosis, where the participants of the 100,000 Genomes Project, as well as the patient's sequenced through the NHS Genomic Medicine Service   This is meant to be more equitable as we don't rely on the clinical teams to raise individual separate requests.  Florence: And finally, what do we mean by secondary findings?   Adrianto: Secondary findings are additional findings not related to the conditions in which the patient was recruited for. For example, if a patient was recruited for one type of cancer, but perhaps we found variants linked to a different condition. We explored secondary findings for the 100,000 Genomes Project but we do not do secondary findings for the Genomic Medicine Service.   Florence: That was Adrianto Wirawan explaining what we mean by ‘no primary findings'. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk.  Thank you for listening. 

Send us a textUnlocking the Secrets of Personalized Nutrition with Amanda Archibald, Nutrigenomics ExpertIn this captivating episode of the Joint Dynamics podcast, host Andrew Cox sits down with Amanda Archibald, the visionary Founder of The Genomic Kitchen, Author of the book of the same name (The Genomic Kitchen), & registered dietitian specialising in the cutting-edge field of nutrigenomics. As a pioneer in this rapidly evolving area, Amanda shares her expertise on how understanding our unique genetic makeup can revolutionise the way we approach health, nutrition, & wellness.Throughout the conversation, Amanda delves into the science behind nutrigenomics, explaining how specific genes, metabolic pathways, and dietary factors interact to influence our body's response to food, movement & mood. She provides practical advice on how listeners can leverage this knowledge to make more informed decisions about their diet, lifestyle, & overall well-being.Listeners will gain valuable insights into personalized nutrition strategies, and how to optimise their “ROI” (Return on INGESTION) with food choices which can powerfully assist addressing potential genetic predispositions to chronic conditions, optimise athletic performance, & enhance mental clarity & cognitive function. Amanda's holistic & practical approach emphasizes the importance of considering an individual's unique genetic blueprint, their lifestyle, & environmental factors when designing targeted nutritional interventions.Whether you're an athlete seeking to enhance your training, a health-conscious individual striving for optimal wellness, or simply someone curious about the transformative power of nutrigenomics, this episode promises to be a game-changer. Prepare to be inspired by Amanda's passion, practicality, & expertise as she guides you through the cutting-edge world of personalised nutrition and unlocks the secrets to further revealing your full genetic potential.Show sponsor is Muvitality Medicinal Mushrooms. Go to muvitality.com and use the code JD10 to receive a 10% discount on your purchase of Mu Functional mushrooms such as Lions Mane, Cordyceps, Chaga, Reishi, and Turkey tailhttps://www.muvitality.com/EnjoyLinks for this podcasthttps://www.genomickitchen.com/who-what-whyIG @genomickitchenLI - https://www.linkedin.com/in/amandaarchibald/Relevant episodesEpisode 106 with Harvard Immunologist Dobri Kiprov on Longevity & Therapeutic Plasma Exchange https://open.spotify.com/episode/3qDLIfHvE7hcr7ugDmQdtj?si=f2c4562fc2184beaEpisode 95 with Futurist, Inventor & Research Scientist Ian Mitchell of Wizard Sciences - https://open.spotify.com/episode/0o82kUirhF5pe5atUn9Hyx?si=d5ac8b4a00c84794JOINT DYNAMICS links:Joint Dynamics Facebook - https://www.facebook.com/JointDynamicsHongKong/Joint Dynamics Instagram -https://www.instagram.com/jointdynamics/Joint Dynamics Youtube - https://www.youtube.com/channel/UCRQZplKxZMSvtc6LxM5WckwJoint Dynamics Website - www.jointdynamics.com.hk Host - Andrew Cox - https://www.jointdynamics.com.hk/the-team/trainers/andrew-

We have New Genomic INFO!

In episode 246, Prep Dish founder Allison Schaaf welcomes Amanda Archibald, dietitian and founder of The Genomic Kitchen, to talk about genes and how they play such a profound role in how our bodies respond to nutrition and food. Amanda talks about the fascinating world of nutrigenetics and nutrigenomics, explaining what they are and how they can be used to manipulate food around genetic patterns.   Connect with Allison: PrepDish.com Instagram: Instagram (@prepdish) Join our FB group- Prep Dish Meal Planning (Gluten Free, Paleo & Keto) | Facebook Resources mentioned in this episode: Genomickitchen.com Gene-ius In Your Kitchen Course: https://www.genomickitchen.com/geneius-experience The Genomic Kitchen Express Course: https://www.genomickitchen.com/the-genomic-kitchen-express-course Fundamentals Course: https://www.genomickitchen.com/self-paced-course Want to try Prep Dish meal plans for FREE? Go to ---> PrepDish.com/MPM

In this episode of the Micro binfie Podcast, host Andrew Page sits down with Tim Dallman at the 10th Bioinformatics Hackathon in Bethesda, Maryland. Tim shares insights from his work at Utrecht University in the Netherlands, where he focuses on genomic surveillance and machine learning models to predict disease risk and severity. They discuss the challenges of integrating genomic variation into predictive models, the importance of high-quality metadata, and the complexities of working with pathogens like Shiga toxin-producing E. coli. Tim also talks about his role at the WHO Pandemic and Epidemic Intelligence Hub and how global collaboration can drive innovation in public health genomics. Tune in to hear about cutting-edge research, the importance of interdisciplinary teamwork, and how genomic data can be harnessed for future pandemic preparedness.

Barney Balmforth's journey is a testament to calculated risk-taking, resilience, visionary leadership, and two pivotal lessons: the importance of taking calculated risks and pursuing meaningful endeavors. These values, along with the inspiration to work hard, drove Barney's career in the high-stakes world of tech and biotech startups. His latest startup, Biofidelity, has attracted funding from top-tier investors like Agilent Technologies, Octopus Ventures, BlueYard Capital, and SBI Investment.

How do Vitamin D and genomic ancestry impact cancer cells? Dr. Moray J. Campbell, a research scientist at Cedars-Sinai Cancer, joins the podcast to explain… Dr. Campbell is a cancer biologist who studies the genomic and epigenomic drivers of hormone-dependent cancers. By utilizing high-dimensional data approaches and bioinformatic analyses, Dr. Campbell is on a mission to uncover the scientific mysteries of cancer. Jump into the conversation now to find out: How Vitamin D and genomic ancestry influences prostate cancer.  How prostate cancer cells bind to patients depending on their genetic makeup. How gene expression in prostate cancer works. Where people get most of their Vitamin D from.  Want to learn more about Dr. Campbell and his research? Click here now! Episode also available on Apple Podcasts: http://apple.co/30PvU9C

The pandemic served as a catalyst for a revolution in genomic surveillance for tracking pathogens. The technology proved vital in aiding understanding of the evolution of and spread of virus in real time to inform public health measures, ultimately accelerating drug and vaccine development. In today's podcast, web editor Nicole Raleigh speaks with Dr Evan Floden, CEO and co-founder of Seqera, a data orchestration and genomics analysis company, about barriers of entry to genomic surveillance in public health labs and how these can be lowered to support future bioinformaticians, aiding acceleration and quality and accuracy in R&D.

A new study reveals human and animal hair in the teeth of the famous ‘man-eater' lions that were killed in 1898, and what we can learn from a rare well-preserved Viking burial site. Plus, on This Day in History, Teddy Roosevelt delivers an hour-long campaign speech in Milwaukee AFTER being shot in the chest. Genomic study identifies human, animal hair in 'man-eater' lions' teeth | ScienceDaily In Denmark, 50 well-preserved Viking Age skeletons have been unearthed, a rare discovery | AP News Teddy Roosevelt survived shooting, assassination attempt in Milwaukee (jsonline.com) Contact the show - coolstuffcommute@gmail.com Learn more about your ad choices. Visit megaphone.fm/adchoices

Advances in DNA sequencing and the vast amounts of genomic data being produced by next-generation sequencing (NGS) technology have created a startup opportunity to build software for biologists so they can more easily analyze this big data and take the next leap. Learn more about your ad choices. Visit podcastchoices.com/adchoices

In this explainer episode, we've asked Amanda Pichini, Clinical Director at Genomics England and Genetic Counsellor, to explain which healthcare professionals you may come into contact with in your genomic healthcare journey. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you've got any questions, or have any other topics you'd like us to explain, feel free to contact us on info@genomicsengland.co.uk. You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/Which-healthcare-professionals-are-involved-in-my-genomics-healthcare-journey.docx  Florence: Which healthcare professionals are involved in my genomic healthcare journey? I'm joined with Amanda Pichini, Clinical Director for Genomics England, and genetic counsellor to find out more. So firstly, when someone has a genetic or genomic test, what kind of healthcare professionals might they come into contact with?  Amanda: Well, everyone has a different journey, and it can depend on the type of test you have and the reason for having it. Some tests might only look for a single gene. Some might look at many genes, and some look for a very specific gene change that's already known to be in someone's family. Some genomic tests are there to find the cause of a person's diagnosis, understand more about their cancer, or maybe to predict a future health problem that they may have or that's in their family.  So usually people start with their GP, who they go to with a question about their health or their child's health, and this could lead to them being referred to a clinical genetic service or perhaps another specialist team.   Florence: So, then what is the purpose of a clinical genetics team?  Amanda: Well, a clinical genetics team, in brief, aims to provide people that have a genetic condition or are at risk of one with health information, including information about prevention, counselling support, and genomic testing, and they focus on the whole family.  Adults and children can both be seen in a genetic service. Clinical genetics teams tend to focus on rare conditions and rare predispositions to certain types of cancers, so really anything that might have a strong genetic basis and could impact someone at any stage of their life. A clinical genetics team is made up of a range of roles, and that could include clinical genetics, doctors, genetic counsellors, clinical scientists, and administrative staff.  Florence: Could you tell me a little bit more about each of those roles?   Amanda: Sure. I am a genetic counsellor, so I'll start with that. Genetic counsellors are specially trained healthcare professionals that help patients and families understand information about their genomic health, as well as provide guidance and emotional support.  So, this could be about understanding their family history, making informed choices about having a genetic or genomic test, or helping them to come to terms with a result or a new diagnosis and the impact that could have on them or their family. Clinical geneticists are medically trained doctors that specialise in genetic conditions.  They understand the underlying ways that genetics can affect health, and they use that to help make diagnoses for patients. How about genomic scientists? These are often not seen directly by patients, but they're vital to someone's genomic healthcare journey. So clinical genomic scientists and genetic technologists work in labs, and they're involved in processing patient samples, working with those other healthcare professionals to select the most appropriate genomic tests to perform and interpreting those results based on the variance or genetic changes that are seen in patients, which are usually summarised in a lab report.  There's lots of other healthcare professionals that can also, um, be in a clinical genetics team. That could include administrative staff, family history coordinators, genomic practitioners or genomic associates. They might help arrange appointments, gather medical and family history details after a referral to help the clinical team know what might be done next.  Some genetic services also have psychologists, nurses, or other allied health professionals embedded in their team or in specialty clinics that they work with, and it's really important that everyone is working together as a multidisciplinary team to help those patients and families in their healthcare journey.  Florence: So, we know there are lots of different healthcare professionals within the clinical genetics team. Are there any other professionals involved in genomic healthcare as well?   Amanda: Absolutely. As genomics becomes part of routine healthcare, that means there's lots of other healthcare professionals involved in arranging genomic tests and giving back results, or at least having initial discussions about genomic tests before referring on to another specialist.  So, some examples might be midwives, arranging screening tests for women in pregnancy, a number of those screening tests have a genetic or genomic basis. They might also refer families with a history of a genetic condition whilst they're pregnant for more specialist genetic testing. Many paediatricians are ordering genomic tests for children that might be suspected to have a syndrome or an underlying cause for their health or developmental issues.  And many nurse specialists like those who work with people with cardiac conditions or neurological conditions. Might be involved in arranging or discussing genetic testing. Final example in the cancer world is oncologists who might often arrange genetic tests that will help give information about someone's cancer.  The last thing to call out isn't necessarily healthcare professionals, but patient charity organisations are super crucial to someone's genetic healthcare journey. It's really important for families when they've had a new diagnosis or when they're seeking information, and there are some charities that do have healthcare professionals that work for them, like a nurse or genetic counsellor or psychologist that may help to run a helpline, for example.  Florence: That was Amanda Pichini explaining which healthcare professionals are involved in a genomic healthcare journey. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

This interview introduces Helen Taylor who has a master's degree in Genomic and Regenerative Medicine in Biomedical Science. Helen made the switch to carnivore lifestyle in February 2024. She talks about how a hysterectomy led her to learn more about diet and nutrition and how epigenetics plays a role in our health. Helen states that our bodies are like a library, remembering everything we put it through. Helen recalls her personal experience with veganism and how it led her to question her health and that lead to studying epigenetics, which can predict disease and trauma. Transitioning to Carnivore improved Helen's overall health, cleared her brain, calmed her down, reduced pain and inflammation, and helped her be more energetic and live in the present. She admits that it took a while for the results to show, but now she feels like she's been given a new life! Helen is a biomedical scientist who specializes in cellular and molecular immunology. She shares how her interest in immune disorders, including thyroid issues and hormone imbalances, led her to focus on personalized medicine. She explains epigenetics and how it can help identify the root causes of health issues, and the importance of addressing environmental toxins, such as glyphosate, in our diet. She also discusses her own journey with a hysterectomy and how it affected her hormones, and how she loves carnivore for its simplicity and effectiveness.

This week on Data in Biotech, we're joined by Mo Jain, the Founder and CEO of Sapient, a biomarker discovery organization that enables biopharma sponsors to go beyond the genome to accelerate precision drug development.  Mo talks us through his personal journey into the world of science, from school to working in academia to founding his business, Sapient. He explains how and why Sapient first started and the evolution of the high-throughput mass-spectrometry service it provides to the biopharmaceutical sector.  Together with our host Ross, they explore the technology that's allowed scientists to explore one's medical history like never before via metabolome, lipidome, and proteome analysis. They look at how the technology developed to allow data testing to go from running twenty tests per blood sample to twenty thousand. How have Sapient built themselves up to such a renowned status in biopharmaceuticals for large-scale data projects? They discuss Sapient's process when working with clients on genome projects. We learn about Sapient's relationship with their clients, how they understand the targets and aims of each project, why they put so much importance on proprietary database management and quality control, and Sapient's three pillars for high quality data discovery. Finally, Mo takes the opportunity to give us his insights on the future of biomarker discovery and mass-spectrometry technology - and how AI and Machine Learning are leading to enhanced data quality and quantity.  Data in Biotech is a fortnightly podcast exploring how companies leverage data innovation in the life sciences. Chapter Markers [1:33] Introduction to Mo Jain, his journey, Genomics, and Sapient's use of Genomics data to accelerate Medicine and Drug Development  [6:50] The types of data generated at Sapient via metabolome, lipidome & proteome, and why that data is generated [12:30] How Sapient generates this data at scale, via specialist mass-spectrometry technology  [14:48] The problems Sapient can solve for pharma and biotech companies with this data [21:03] Sapient as a service company: the questions they're asked by pharmaceutical businesses, why they come to Sapient, and Sapient's process for answering those questions.  [26:23] computational frameworks and data handling side of things, and how the team interact with the client [29:59] Proprietary database development and quality control  [35:27] The future of biomarker discovery and mass-spectrometry technology, and how AI and Machine Learning are leading the way at Sapient

In this episode of the Vital Health podcast, we dive deep into the world of genomic data and its transformative impact on healthcare. Join host Duane Schulthess as he sits down with Judsen Schneider, CTO of Nashville Biosciences, and Curt Allen, VP of Sales, to explore the origins and growth of Nashville Biosciences. Discover how this pioneering company, in collaboration with Vanderbilt University, is leveraging vast amounts of clinical data to drive innovation in drug development and treatment strategies. Learn about the unique healthcare ecosystem in Nashville, the challenges of coastal bias, and the significant role of data diversity in their success. The discussion also touches on the evolving landscape of AI in healthcare, the global reach of their data, and what the future holds for genomic discovery. Whether you're a healthcare professional, biotech enthusiast, or just curious about the future of medicine, this episode is packed with insights you won't want to miss!Don't forget to like, comment, and subscribe for more episodes of the Vital Health podcast!See omnystudio.com/listener for privacy information.

Aldo de Pape, co-founder and CEO of Genomes.io, joins The Agenda podcast to discuss the genomic mapping industry's privacy challenges and their impact on users, including why people should be more cautious with their genetic data amid an atmosphere of hacks and companies selling your DNA data.The Agenda is brought to you by Cointelegraph and hosted/produced by Ray Salmond and Jonathan DeYoung. Follow Cointelegraph on X (Twitter) at @Cointelegraph, Jonathan at @maddopemadic and Ray at @HorusHughes. Jonathan is also on Instagram at @maddopemadic, and he makes the music for the podcast — hear more at madic.art.Follow Aldo on X @aldodepape and Genomes.io at @genomesdao.Check out Cointelegraph at cointelegraph.com.(00:00:00) Introduction to The Agenda podcast and this week's episode(00:01:34) What is genetic sequencing?(00:03:21) What sets Genomes.io apart from its competitors?(00:07:29) The genomic sequencing industry is still the Wild West(00:14:13) Aldo's thoughts on why the industry needs a universal regulatory framework(00:16:06) Not protecting your data could make you the next Henrietta Lacks(00:18:56) How do users know that the Genomes.io platform is secure? (00:22:29) How Genomes.io data sourcing and compensation work(00:25:04) Genomic mapping use case examples(00:27:47) Why does the project have a token and a DAO?(00:42:06) The future role of AI and quantum computing in genomicsIf you like what you heard, rate us and leave a review!The views, thoughts and opinions expressed in this podcast are its participants' alone and do not necessarily reflect or represent the views and opinions of Cointelegraph. This podcast (and any related content) is for entertainment purposes only and does not constitute financial advice, nor should it be taken as such. Everyone must do their own research and make their own decisions. The podcast's participants may or may not own any of the assets mentioned.

Welcome to episode 059 of Life Sciences 360.In this episode of Life Sciences 360, Harsh Thakkar is joined by John Finn, Chief Scientific Officer at Tome Biosciences. John shares his inspiring journey of overcoming challenges, like his stutter, while making groundbreaking strides in gene therapy. They dive deep into Tome's unique technology, PGI (Programmable Genomic Integration), which is revolutionizing how large-scale gene insertions are done with pinpoint accuracy. Learn how Tome Biosciences is leading the charge in curing genetic disorders and advancing cell therapy with cutting-edge science.Chapters:00:00 - Introduction to the Episode00:29 - The Vision Behind Gene Therapy01:13 - John's Journey and Challenges with Stuttering03:14 - How Stuttering Shaped John's Career in Science05:43 - Introduction to Tome Biosciences07:02 - The Origins of Tome and Founding Vision09:49 - Why Large-Scale Gene Editing Matters14:12 - How Tome's PGI Technology Works20:29 - What Sets Tome Apart in Gene Therapy24:31 - Future Milestones for Tome Biosciences30:49 - Overcoming Challenges in Genomic Integration36:47 - The Power of Team Culture at Tome Biosciences40:20 - Advice for Aspiring Scientists and Entrepreneurs42:52 - Where to Connect with John Finn and Learn More About Tome- Follow John Finn: *Linkedin - ( https://www.linkedin.com/in/jonathan-john-finn-8b3bb23/ ) *Tome Bio Linkedin -  ( https://www.linkedin.com/company/tome-biosciences/ ) * Tome Bio Website- ( https://tome.bio/ )---Links:*Harsh Thakkar LinkedIn ( https://www.linkedin.com/in/harshvthakkar/ )*Listen to this episode on the go! 

In this episode, we delve into the impact of the new groundbreaking research uncovering the RNU4-2 genetic variant linked to neurodevelopmental conditions. The discovery, made possible through whole genome sequencing, highlights a genetic change in the RNU4-2 gene that affects about 1 in 200 undiagnosed children with neurodevelopmental conditions, making it more prevalent than previously thought. This discovery represents one of the most common single-gene genetic causes of such conditions. Our host, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Lindsay Pearse who shares her journey through the diagnosis of her son Lars. They are also joined by Sarah Wynn, CEO of Unique, and Emma Baple, Clinical Genetics Doctor and Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub. We also hear from the 2 research groups who independently discovered the findings: Dr Andrew Mumford, Professor of Haematology at the University of Bristol Link to the research paper: https://www.nature.com/articles/s41591-024-03085-5  Assistant Professor Nicky Whiffin, Big Data Institute and Centre for Human Genetics at the University of Oxford Link to the research paper: https://www.nature.com/articles/s41586-024-07773-7 To access resources mentioned in this podcast:  Unique provides support, information and networking to families affected by rare chromosome and gene disorders - for more information and support please visit the website. Connect with other parents of children carrying a variation in RNU4-2 on the Facebook group.   "I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future."   You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/How-has-a-groundbreaking-genomic-discovery-impacted-thousands-worldwide.docx  Naimah: Welcome to Behind the Genes. Lindsay: So, this feeling that like we've been on this deserted island for eight years and now all of a sudden, you're sort of looking around through the branches of the trees. It's like, wait a minute, there are other people on this island and in this case actually there's a lot more people on this island. Yeah, it's very exciting, it's validating. It gives us a lot of hope and, you know, it has been quite emotional too and also a bit of an identity shift. Being undiagnosed had become quite a big part of our identity, and so now that's kind of shifting a little bit that we have this new diagnosis and are part of a new community. Naimah: My name is Naimah Callachand and I'm Head of Product Engagement and Growth at Genomics England. On today's episode, I'm joined by Lindsay Pearse whose son Lars recently received a genetic diagnosis, made possible by research using data from the National Genomic Research Library, Sarah Wynn CEO of Unique, and Emma Baple, a clinical genetics doctor. Today we'll be discussing the impact of recent research findings which have found a genetic change in the non-coding RNU4-2 gene, to be linked to neurodevelopmental conditions. If you enjoy today's episode, we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. Naimah: And first of all, I would like everyone to introduce themselves. So, Lindsay, maybe if we could come to you first. Lindsay: Great, thank you. So, thank you for having me. I'm Lindsay Pearse, I live outside of Washington DC and I'm a mum to 3 boys. My oldest son Lars who is 8, he was recently diagnosed with the de novo variant in the RNU4-2 gene. Naimah: Thank you. And Emma? Emma: My name is Emma Baple. I'm a Clinical Genetics Doctor which means I look after children and adults with genetic conditions. I'm also a Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub. Naimah: And Sarah? Sarah: Hi, thank you for having me. I'm Sarah Wynn, I'm the CEO of a patient organisation called Unique, and we provide support and information to all those affected by rare genetic conditions. Naimah: Great, thank you. It's so great to have you all here today. So, first of all Lindsay, I wonder if we could come to you. So, you mentioned in your introduction your son Lars has recently been diagnosed with the de novo variant. I wondered if you could tell us a bit about your story, and what it's been like up until the diagnosis. Lindsay: Sure, yeah. So, Lars is, he's a wonderful 8 year-old boy. With his condition, his main symptoms he experiences global developmental delays, he's non-verbal. He's had hypertonia pretty much since birth and wears AFO's to support his walking. He has a feeding disorder and is fed by a G-Tube. Cortical vision impairments, a history of seizures and slow growth, amongst other things. So, that's just a bit of a picture of what he deals with day to day. But he's my oldest child, so first baby. When I was pregnant, we were given an IUGR diagnosis. He was breech, he had a hernia soon after birth, wouldn't breastfeed. But all of these things aren't terribly uncommon, you know. But once he was about 3 or 4 months old, we noticed that he wasn't really able to push up like he should, and we were put in touch with early intervention services for an assessment. So, we went ahead and did that when he was about 4 or 5 months old. And as parents, we could just kind of tell that something was off from the assessors. And, you know, they were very gentle with us, but we could just get that sense that okay, something is off, and they're worried here. So, that kind of kickstarted me into making appointments left, right and centre with specialists. The first specialist that we saw was a neurologist. And yeah, again, that's another appointment that I'll never forget. She referred us to genetics and to get an MRI and some lab work but at the end of the appointment, she said to us, ‘Just remember to love your child.' And, you know, that was quite shocking to us at the time because it wasn't something that had ever crossed our mind that we wouldn't do or felt like we needed to be told to do this. But on the other hand, it certainly set off a lot of worry and anxiety of okay, well, what exactly are we dealing with here? So, fast forward, we saw genetics and that was about when Lars was about 8 months old. We went through a variety of genetic testing, a chromosomal micro-array, a single gene testing, then the whole exome testing. Everything came back negative, but it was explained to us that what was going on was likely an overarching genetic diagnosis that would explain his like, multi-system symptoms. And so meanwhile as he was getting older his global delays were becoming more pronounced and we were also in and out of the hospital a lot at this time. At first, he was in day care and, you know, any sort of cold virus would always turn into like a pneumonia for him. So, we were just in and out of hospital seeing a myriad of specialists, trying to put together this puzzle of what's going on and it was really hard to accept that nobody could figure it out. That was just, you know, sort of mind-blowing to us I guess. So, we applied for and were accepted into the Undiagnosed Diseases Programme at the National Institute of Health over here. The NIH as it's commonly referred to. So, we first went there when Lars was 2. He was one of their youngest patients at the time. But that was a really great experience for us because we felt like they were looking at him holistically and across a bunch of all of his systems, and not just seeing a specialist for sort of each system. So, we really appreciated that. We also did the whole genome sequencing through this research study. Although that also came back negative and so at that point, we were told to kind of keep following up symptomatically. Keep seeing the specialists and eventually maybe one day we'll find an overarching diagnosis, but that science just hadn't quite caught up to Lars. It was hard for me again to believe that and to sort of wrap my head around that. But certainly, it was an education from all of the doctors and geneticists and everyone we saw at NIH, to realise like how far there still was to go in terms of genetic research. How it wasn't also that uncommon to be undiagnosed in the rare disease community. I would say that being undiagnosed sort of became part of our identity. And it's, you know, it was something that, you know, you had to explain to like insurance companies and to his school, and it became part of our advocacy around him. Because without being able to say oh, it's this specific thing and if it was someone who hadn't met Lars before, trying to explain to them that, you know, yeah, within the range of this community you can be undiagnosed, and they just haven't found it yet, but I promise you there is something going on here. And I'd say the other thing too without a diagnosis you have no prognosis, right? And so, trying to figure out what the future would look like. Also, family planning. We waited 5 and a half years before we had another child and, you know, it was certainly an anxiety ridden decision. Ultimately after seeing as many specialists as we possibly could, we still were left with the same answer of well, we just don't really know if it will happen again. So, that was a big decision to make. But again, it just kind of became part of our identity and something that you did eventually accept. But I would say in my experience I feel like the acceptance part also of Lars' disabilities perhaps took me a little bit longer. Because again, I didn't have a prognosis, so I didn't exactly know what we were dealing with. Only as he has become older and, you know, you're sort of getting a better sense of what his abilities might be than being able to understand, okay, this is what I'm dealing with. I need to accept that and do what I can to care for him and our family in the best way that we can. Naimah: Thanks so much for sharing that, Lindsay. I feel like you've touched on a lot of really, you know, a lot of complications and difficulties for your family. Especially, you know, with regards to keeping hopeful and things about the prognosis as well, I'm sure it was really difficult. You've mentioned that Lars was able to be diagnosed recently due to recent research efforts. So, Sarah, I wonder if you can tell us a bit more about these and what the findings have meant for patients with neurodevelopmental conditions. Sarah: Yes. So, I think we know that there are lots of families that are in Lindsay and Lars' position where they know that there is almost certainly an underlying genetic condition, and it just hasn't been found yet. And so, I think we know that lots of researchers are working really hard to try and find those causes. I think over time we know that as time goes on and research goes on, we'll find more of these new genetic causes for neurodevelopmental conditions. I think particularly as we start to look at regions of the genome that we haven't looked at so much so far. But I think one of the things that's really extraordinary about this one is that actually it turns out to be much more common than we might have expected, for one of these new conditions that we haven't found before. But I think it's about one in 200 of those undiagnosed children with neurodevelopmental conditions, have this diagnosis so that's not a small number. That's not a rare finding at all actually, that's much more common than we could ever have anticipated. But I think one of the things that we do know is that as we look further and deeper into that genomic sequence, so, we've started off looking at the bits of the sequence that are genes that code for proteins. This changes in a gene that actually doesn't code for protein, so it's less obvious that it would be important but clearly it is important in development because we know when it has a spelling mistake in it, it causes this neurodevelopmental condition. But there will be as researchers look more and more at these kinds of genes, and also the other part of the genome that is not genes at all, we'll find out more and more the underlying genetic causes of these neurodevelopmental conditions. I think it's also really important to stress why this is so important to find these genetic changes and it's because families really need a diagnosis. Lindsay talked quite eloquently and a lot about that knowing something was off and really wanting to know the reason why. Getting these diagnoses might change care management or treatment, but actually really importantly it just gives an answer to families who have often been looking for an answer for a really long time. Naimah: I just wanted to go back to the point that Sarah made that actually this genetic change is relatively common. Emma, I wondered if you could tell us a bit more about maybe why it took us so long to discover it? Emma: That's an interesting question actually. I suppose the sort of slightly simplified answer to that question is we haven't been able to sequence the whole of a person's genetic information for that long. And so, children like Lars would have had, as Lindsay described lots and lots of genetic tests up until they had a whole genome sequencing which is what Sarah was talking about. The types of tests that we had up until the whole genome sequencing wouldn't have allowed us to look at that bit of the genetic code where this RNU4-2 gene can be found. So, we can only really find that using whole genome sequencing. So, before that existed, we wouldn't have been able to find this cause of developmental condition. Naimah: Okay, thanks Emma. Naimah: Now we're going to hear from one of the two research groups who are responsible for these research findings. First of all, let's hear from Nicky Whiffin. (Clip - Nicky Whiffin) Naimah: How were the findings possible using the Genomics England dataset? Nicky: So, most previous studies have only looked at genetic variants that, in genes that make proteins, but only a subset of our genes actually do makes proteins. The Genomics England dataset we have sequencing information on the entire genome, not just on these protein coding genes and that means we can also look at variants in other genes. So, those that make molecules other than proteins. And RNU4-2 for example, makes an RNA molecule. Naimah: These findings translated to direct patient benefit for patients like Lars who were able to receive support from Unique. How does this demonstrate the value of the dataset? Nicky: Yes. So, it was incredible that we could find so many patients with RNU4-2 variants so quickly. This was enabled by access to Genomics England data but also to other large sequencing datasets around the world. So, we worked with people in the US, in Australia and also in mainland Europe. These large datasets enabled us to spot consistent patterns in the data and by looking across multiple datasets we can also make sure that our findings are robust. When we realised how significant this was and how many families would be impacted, we very quickly contacted Sarah at Unique to see if we could direct patients to them for support. (End of clip) Emma: There's one thing I wanted to raise. It's important to recognise the way that was discovered was through the National Genomic Research Library that Genomics England hosts. To highlight the value of that, and the value of having this centralised resource where families have been kind enough really to allow their data to be shared with some limited clinical information that allowed these researchers to be able to pull this out. And I think it highlights the power of the National Health Service in that we were able to create such a resource. It's really quite astounding that we've found such a common cause of a rare genetic condition, and it wouldn't have happened in the same timescale or in this way without that resource. And then to just say that as Sarah talked about the fact that we've been able to get that information out there, also the researchers were able to get out there and contact the NIH and all of these other programmes worldwide. In Australia, America, everywhere in the world and quickly identify new patients who had this condition and get those diagnoses out really rapidly to people. But all that came from that power of sharing data and being able to have that all in one place and making it accessible to very clever people who could do this work and find these answers. It's so important for families like Lindsay's, and all the families in England and around the world that have got these answers. So, I guess it's a big plug for the value of data sharing and having a secure place where people feel that it's trusted and safe, that enables these diagnoses to be made. Lindsay: If I could just echo that, we're so grateful that that exists in the UK. Just acknowledging like the privilege here that we have had to be able to, I mean for our family in the US, that we've been able to, you know, get ourselves into the NIH study and into the study at Children's National. That takes a lot of work. I feel like not everybody has that opportunity to be able to spend the time to do these applications and to go to all the appointments and get the testing done and have the insurance to cover it. So, very grateful that the system exists in a way in the UK that made this sort of research possible. I just hope that that can be replicated in other places, and also to what Emma was saying earlier, come up with a lower cost test as well for this to further the growth of the community and of course then the corresponding research. Sarah: I think firstly we have to sort of thank all of those families that took part and do share their data, because I think it's not always clear why you might want to do that as a family. I think this is really a powerful example of the benefit of that. I also think the data sharing goes one stage further. So, it's partly about getting the diagnosis, but the data sharing going forward about how this condition impacts families, both clinically and sort of day to day lived experience, is how we'll be able to learn more about these conditions. And so, when families get this diagnosis next week or next year, not only will they get a diagnosis, but they'll get a really good idea about what the condition is and how it might impact their child. Naimah: And Lindsay, coming back to you. So, we've talked about, you know, what it meant for your family before the diagnosis, but what has it meant to have a diagnosis and how did you feel? And what happened whenever you received the diagnosis? Lindsay: Sure. Lars was again part of the NIH Undiagnosed Diseases Research study. So, once you attend this programme and if you are not diagnosed like at the end of your stay, they keep your details on file and you're part of this database at the NIH Undiagnosed Diseases Programme. So, if you're undiagnosed after your sort of week-long work up, your samples stay within the research programme. We were also part of a research programme at Children's National Medical Centre, the Rare Disease Institute. So, our samples were sort of on file there in their database as well. And so, at the end of March I was really quite shocked to receive a call from our long time and trusted geneticist at Children's National that they had found a diagnosis. It was quite emotional. I really kind of didn't believe it. I just kept asking, you know, ‘Are you sure? Is this it?' you know, ‘How confident are we?' Because I think in my head, I sort of always thought that we would eventually find a diagnosis, but I thought that Lars would be, you know, a 30- or 40-year-old adult. I thought it would be decades from now. Like I felt like for whatever reason we had to wait decades for the science to sort of catch up to him. So, we were very, very grateful. It felt very validating, I guess. I had always kind of had this intuition feeling that we were sort of missing something and it's more that the science just hadn't quite caught up yet. But, you know, it was validating to know that okay, Lars is not the only person in the entire world with this, it is something that is relatively common in fact within the rare disease community. That is also very exciting to me personally because I'm hopeful that that will lead more researchers to be interesting in this, given how, quote on quote, common it is. I've sort of been describing it as like a mass diagnosis event but also more so this feeling that like we've been on this deserted island for eight years and now all of a sudden, you're sort of like looking around through the branches of the trees. It's like, wait a minute, there are other people on this island ad in this case, there's actually a lot more people on this island. Yeah, it's very exciting, it's validating. It gives us a lot of hope. And, you know, it has been quite emotional too and also a bit of an identity shift. Because I spoke earlier about how like being undiagnosed had become quite a big part of our identity. So, now that's kind of shifting a little bit that we have this new diagnosis and are part of a new community. But yeah, we're just very grateful that the research had continued. And, you know, I think sometimes you sort of have this feeling of okay, our files are up on a shelf somewhere, you know, collecting dust and are people really looking at them? And actually, it turns out that the research was ongoing and yeah, we're just very grateful for that. Naimah: Thanks so much for sharing, Lindsay. It sounds like it's been a real rollercoaster of emotions for your family and I'm glad to hear that, you know, you've got some hope now that you've got a diagnosis as well. So, moving onto the next question. Emma, I wanted to ask you then, how will these findings improve clinical diagnostic services for those for neurodevelopmental conditions? Emma: So, you asked me earlier about why it had taken so long to find this particular cause of neurodevelopmental condition, and I gave you a relatively simple answer. The reality is one of the other reasons is that almost eight out of ten children and adults who have RNU4-2 related neurodevelopmental condition have exactly the same single letter spelling change in that gene. So, actually that in itself means that when researchers are looking at that information, they might think that it's actually a mistake. Because we know that when we sequence genetic information, we can see mistakes in that sequencing information that are just because the machine has, and the way that we process that data, it's not perfect. So, sometimes we find these little mistakes and they're not actually the cause of a person's problems, they're just what we call an artefact or an issue with the way that that happens. So, that is part of the reason for why it was tricky for us to know whether this was, or rather the researchers to know whether this was or was not the cause of this particular condition. But that in itself is quite helpful when we think about how we might identify more people who have this going forwards. Because unlike in Lars' case where we didn't know what the cause was and so we were still searching, and we didn't know where to look in the billions of letters that make up the genetic code to find that answer, we now know that this is really very common. It's unbelievably common. I think we didn't think we would be finding a cause of a rare genetic condition that was this commonly occurring at this stage. But the fact that it's just a single, it's commonly this one single change in the gene means that we can set up pretty cheap diagnostic testing. Which means that if you were somewhere where you wouldn't necessarily have access to whole genome sequencing, or a more comprehensive testing in that way, we could still be able to pick up this condition. And it's common enough that even if you didn't necessarily recognise that a person had it, you could still have this as part of your diagnostic tool kit for patients who have a neurodevelopmental condition. It's common enough that just doing a very simple test that could be done in any diagnostic lab anywhere in the world, you would be able to identify the majority of people who have this. Naimah: Now let's hear from the other research group who are responsible for these findings. Here is Dr Andrew Mumford. (Clip - Dr Andrew Mumford) Naimah: Why are these research findings significant? Andrew: It offers genetic diagnosis not just for a handful of families but potentially for many hundreds of families, who we all know have been searching often for many, many years for a genetic diagnosis. But actually, there are other gains from understanding how this gene causes neurodevelopmental disorder. We know that there's GRNU4-2 in codes, not a protein actually, but a small nuclear RNA which is unusual for rare, inherited disorders. It's a component of a very complicated molecule called the spliceosome which in turn regulates how thousands of other genes are regulated, how they're made into proteins. So, fundamentally this discovery tells us a lot about the biology of how the spliceosome works. We already know that some other components of the spliceosome can go wrong, and result in diseases like neurodevelopmental disorders. This gives us an extra insight and actually opens the door to, I hope, a whole load of more discoveries of genetic diagnosis possible from other components of this complicated molecule. Naimah: Your research group used a mathematical modelling approach. Can you tell me a bit about this, and what this means for other rare conditions, Andrew? Andrew: So, identifying relationships between changes in individual genes and different kinds of rare, inherited disease is notoriously difficult because of the volume of data that's involved and the need to be absolutely certain that observed genetic changes are actually the cause of different rare, inherited disease. So, applying statistics to that kind of problem isn't new. But what my collaboration group have achieved here, is to develop, actually developed some years ago a completely new approach to applying statistics to genetic data. We call that BeviMed and we've been working for many years on the genes in code that make individual proteins. Most rare disorders are caused by genetic changes in genes that make proteins. What this discovery comes from is actually we've applied the BeviMed statistical technique to genes that don't make proteins, they're non-coding genes. For example, genes that make small nuclear RNA, it's just like RNU4-2. What's unusual about the BeviMed approach is that it's very sensitive to detecting links between genetic changes and rare diseases, and it can detect statistical associations really driven by very, very small numbers of families. So, we apply it to datasets like the 100,00 Genomes dataset and identify associations using statistics that have got a very high probability of association. Other members of the team then seek to corroborate that finding by looking at if we can see the association in other datasets, and we certainly achieve that with RNU4-2. But also, assessing biological plausibility by investigating what we understand already about in this case, a small nuclear RNA, and how it can possibly result in a disease. And we normally try and employ other independent evidence such as experimental investigation. Or going back to our families and asking for additional data to help really test this sort of theory that changes in this particular gene have resulted in a problem with neurodevelopment. (End of clip) Naimah: Emma, are there any other ways that we can identify these conditions based on their clinical presentation? Emma: So, Lindsay and I were talking with you just yesterday, wasn't it? And I asked Lindsay about what sorts of things Lars had in common with other children and adults who have been diagnosed with this condition? I actually think Lindsay probably gives a better summary than I would, so I might ask you to maybe repeat what you said to me yesterday. But the bit of it that really stood out to me was when you said to us that a lot of parents have said, ‘I'm not sure how we weren't all put together in the first place because you notice so many things that were in common.' So, maybe if you can give that summary and then I can translate that back into medical terms, if that's okay Lindsay. Lindsay: Sure, of course. Yeah, it been again, kind of mind blowing, some of the similarities. Especially as we've exchanged pictures and such, and baby pictures especially where some of the children like look like siblings. So, definitely some similarities in facial features, you know, everyone seems to experience some of the slow growth, so a short stature or quite skinny. There's feeding issues also that seem to be quite common. Also, you know, things like the global developmental delays, that's certainly across the board and histories of seizures, that's also quite common. Some people have experienced also some, like, bone density issues, that's not something that we've experienced so far, but that also seems to be quite common. But then also, behaviourally, there's a lot of similarities which has been, I think, quite exciting to a lot of us because you've always thought okay, so this is just my child. And of course, some of that is true but it's also interesting to find out some of these other things that are, you know, are quite similar. So, a lot of people have mentioned their child having, like, an interesting sense of humour. Kind of like a very slapstick sense of humour which is quite interesting. Or everyone seems to love water, everybody loves swimming pools and bathtime, and all of that. Lars loves a windy day. Something about the wind, he just loves it and plane noises and things like that have also come up with other people. So, yeah, it's been really interesting and cool to see. Emma: So, I guess Lindsay's sort of very beautifully summed up what is written in the research publication. So, there's only two research publications so far on this condition, it's all really new. And I am definitely not claim to be a clinical expert on this condition, and I don't think there are any yet. It will take people time to see lots of children and adults who have this particular condition. But ultimately what Lindsay summarised was the common clinical features that have been described by parents. In my job as a clinical genetics doctor, part of what we look at is a person's appearance. So, Lindsay described the photographs of children particularly when they were little, looked very similar. In the photographs that I've seen, I would agree with that. And so obviously those children look like their mum and dad, but they have other features that are in common. They have a characteristic appearance and that helps doctors like me to have an idea as to whether a child or an adult might have a particular condition. Then put together with the sorts of information that Lindsay gave us around the low tone, so being a little bit floppier particularly when they're little. The slow growth and growth problems, problems with eating, also with seizures. Those are all common things that were pulled out of both of the two research publications on this condition and putting that all together into one picture helps doctors to have an idea whether somebody may have a particular condition. That would help us in this case to potentially request that simple test I was talking about, if maybe we were practicing in a part of the world where we wouldn't have the resources that we thankfully do have in the United Kingdom, and in the USA. Naimah: So, Sarah, just coming to you next. How does this research spread awareness and help other patients with these conditions? Sarah: So, I think one of the things that's been really great about research now is that we are able to, you know, social media and things like that mean that we can spread this information really quickly across the world basically. I think what that does is that as well as helping bring people together that they've got this diagnosis, what it does is I think it provides hope for all of those people that Lindsay was talking about at the beginning who don't have a diagnosis. So, that piece around people are still looking, the researchers are working hard and that even if you don't have a diagnosis today you might get one in the future. Lindsay talked about your sample being dusty and not being looked at. I think it gives lots of families, not just those that get this diagnosis but all of those that haven't got a diagnosis, hope, that hopefully in the future they will get a diagnosis. I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future. That prognosis information that Linsday said is really missing when you don't have a diagnosis. And I think the other thing that hopefully is the next stage in this journey with this discovery is that those two science publications that Emma talked about, what we will want to do here at Unique working with the researchers and those families that have got a diagnosis, is to produce a patient family friendly information leaflet about this condition. One of the things we know is really important about those patient leaflets is including the photos. Because as both Emma and Lindsay have said that idea that they have facial features in common. And so, if you look at a leaflet and you can recognise your child in it, and you can see others that look like it, that can be a really sort of quite heartwarming experience in what often is a lonely experience with a rare condition. Naimah: And I think kind of on that point about it being a lonely experience, I wondered Lindsay if you could talk a bit more if this research has allowed you to connect with other parents and families who have received a diagnosis, and what impact that's had on your family? Lindsay: Yeah. I mean, and I think everything that Sarah has said was spot on. It's wonderful to have resources like Unique to connect families and have those diagnoses on the platform, so other clinicians can look for it and sort of grow this group. I think that has definitely been the highlight of getting this diagnosis at this stage, right. Because there's not much more you can do with it, with someone so brand new so being able to connect with the other families has been wonderful. One amazing mum who with this diagnosis set up a Facebook group, RNU4-2 Family Connect. And, you know, it's just been amazing to see people from all over the world joining this as they receive this diagnosis, you know, sharing their stories. We've spent countless hours on the weekends over the past couple of months on Zoom calls with total strangers, but just you find that you can just talk for hours and hours because you have so much in common. It's great to see what has worked well for other families and, you know, what has not worked. Sharing resources, just kind of all learning together. Also seeing the spectrum of this diagnosis, I think most genetic disorders have a spectrum and this seems to be the same here. So, that's been very interesting. And of course, our son is 8, Lars is 8. There's now a 33-year-old and a 29-year-old in the Facebook group. Speaking for me personally it's just amazing to see them and like it's very cool to see where they're at. That sort of helps you answer some of those questions about that before were quite unknown when you were thinking about the future. Obviously, everybody's development whether you have a genetic disorder or not, it is going to be what it's going to be, and everybody is going to do their own thing. But being able to see what a path might look like is just so helpful. And, you know, we all want community and connection, and so this has been really, really great to have that now. Sarah: I don't think there's much more that I can add because Lindsay articulated so well. But it's really heartwarming for us to hear the benefits of those connections because that's really why Unique and other support groups exist. Is to provide, partly to provide information, but I think predominantly to put families in touch with other families so that they can find a new home and connect and share experiences. And, you know, stop feeling as alone as they might have done before. Naimah: Okay, we'll wrap up there. Thank you to our guests, Lindsay Pearce, Sarah Wynn and Emma Baple for joining me today as we discussed the research findings which found a genetic change in the RNU4-2 gene which has been linked to neurodevelopmental conditions. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin of Ventoux Digital.

Jasmin, Janet and Reese talk about controversial changes to how residents can and can't get trees cut down in Westchester, the police murder of a Black woman in Illinois who called 911 for help, the violent state crackdown on student protesters in Bangladesh, and advances in cancer treatment for children.

In Episode 093 of the #kilnroadtrip, created and produced by The Swell Pod, hosts Spencer McKeown and Josh Taylor interview Julie Collens, VP Commercial Operations AMR at Oxford Nanopore Technologies   Check out today's episode and every other installment of the Kiln.Roadtrip by listening, watching, and subscribing to the podcast here - https://linktr.ee/theswellpod   Location: Kiln. Leucadia   The Kiln Road Trip: Uncovering Deep Truths with 100 Pleasantly Rebellious Humans. 10 days. 5 States. 3,580 Miles.100 Interviews! Daily episodes starting on March 5, Monday to Friday, for the next 100 days, followed by a short documentary and a book about the journey.   Thank you to the partners and sponsors who made the kiln.roadtrip possible: KILN, MOTERRA, TORUS   And thank you to the crew who helped us document and share the journey: DENISSE LEON, TY COTTLE, NATHAN CLARK, FINDLAY MCKEOWN   #SwellPod, #KilnRoadTrip, #Kiln, #MotorraCamperVans, #podcast, #interview, #innovation, #resilience, #communitybuilding, #passion, #purpose, #community, #diversity, #collaboration, #thoughtleadership, #100interviews, #entrepreneur, #CEO, #leadership

In this episode, CJ dives deep into one of the hallmarks of aging: genomic instability. Whether you're new to biohacking or a seasoned enthusiast, understanding genomic instability is crucial for promoting longevity and a healthy life.What is Genomic Instability?Genomic instability refers to the increased rate of mutations within our genes. These mutations can be caused by various factors such as environmental toxins, radiation, and the natural process of cell division. Over time, these genetic changes accumulate and contribute to age-related diseases and conditions.Key Concepts Discussed:DNA Replication Errors: Every time a cell divides, it copies its DNA. This process isn't perfect, leading to replication errors that accumulate over time.Oxidative Stress: An imbalance between free radicals and antioxidants in the body can damage DNA, leading to mutations.Environmental Factors: Exposure to UV radiation, pollution, and toxins can directly damage DNA.Impact of Genomic Instability: Conditions like cancer and Alzheimer's disease are linked to accumulated DNA damage and genomic instability.How to Protect Your DNA:Diet: Consuming antioxidant-rich foods like berries, leafy greens, and protein-packed foods can help neutralize free radicals.Exercise: Regular physical activity can repair DNA damage and reduce the risk of mutations by boosting enzymes that maintain DNA integrity.Quality Sleep: Adequate sleep is essential for DNA repair, with melatonin playing a crucial role as a powerful antioxidant.Avoid Toxins: Reducing exposure to environmental toxins like cigarette smoke and UV radiation can prevent DNA damage.Lifestyle Practices: Traditional practices like qigong and Ayurveda offer natural ways to support antioxidant systems and protect against DNA damage.Recommended Supplements:NAD Precursors: Molecules like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) boost NAD levels, crucial for DNA repair and energy production.Resveratrol: Found in red wine, resveratrol protects against DNA damage by activating proteins that maintain DNA integrity.Vitamins C and E: These antioxidants help neutralize free radicals and protect against oxidative stress and membrane damage.Biohacking Tools:Red Light Therapy: Stimulates cellular repair processes and enhances mitochondrial function.Cryotherapy: Reduces inflammation and oxidative stress, promoting DNA repair.Hyperbaric Oxygen Therapy: Increases oxygen levels in the blood, encouraging DNA repair and reversing aspects of aging.Key Takeaways:Start with Your Diet: Focus on incorporating antioxidant-rich foods into your daily meals.Exercise Regularly: Aim for moderate physical activity to boost DNA repair processes.Prioritize Sleep: Ensure you get quality sleep to support overall health and DNA repair.Minimize Toxin Exposure: Avoid harmful environmental factors to protect your DNA.Explore Traditional Practices: Consider incorporating practices like qigong and Ayurveda for additional support.Understanding and addressing genomic instability can significantly enhance your health and longevity. Small, consistent changes lead to long-term benefits.

References J Biomed Sci 2017. 24, 63. Cell Death & Disease 2014. volume 5, page e1416 Haematologica. 2022 Mar 1; 107(3):721–732 Nucleic Acids Res. 2022 Jan 7; 50(D1): D413–D420 Oncogene 2017. volume 36, pages 5593–5608 Cell. 2021 Apr 1; 184(7):1790–1803.e17. Van Zant and Collins. 1973. "Tuesday's Gone" Lynyrd Skynyrd. https://youtu.be/LJrFxnvcWhc?si=EoL42Pw72Qe_atsz Lennon-McCartney. 1967. "I am the Walrus" Beatles. [Magical Mystery Tour, lp.] https://youtu.be/Ws5klxbI87I?si=QGe84-nMLK4dqgFy Hayward, J. 1967. "Tuesday Afternoon" [Days of Future Passed lp.] Moody Blues https://youtu.be/jmMPBQ4kYKk?si=FjZfDQ6KwCNecphw Mendelsshon, F. 1842 Wedding March C major op 61. https://youtu.be/Z-yUOBft96Y?si=ldxpuxPYTlAExXez --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

This episode we chat about the thousands of frog ancestors whose stories can still be heard in the DNA of modern frogs. How did these frogs from the past deal with dramatic changes, and is modern urbanisation having a sizable effect today? Become a Patreon: https://www.patreon.com/herphighlights Merch: https://www.redbubble.com/people/herphighlights/shop Full reference list available here: http://www.herphighlights.podbean.com Main Paper References: Moran PA, Bosse M, Mariën J, Halfwerk W. 2024. Genomic footprints of (pre) colonialism: Population declines in urban and forest túngara frogs coincident with historical human activity. Molecular Ecology 33:e17258. DOI: 10.1111/mec.17258. Editing and Music: Podcast edited by Alex – https://www.fiverr.com/alexanderroses Intro/outro – Treehouse by Ed Nelson Species Bi-week theme – Michael Timothy Other Music – The Passion HiFi, https://www.thepassionhifi.com

Welcome to a brand-new Family Edition of The Tony Robbins Podcast! Join Tony Robbins, his wife Sage Robbins, and their dear friend and podcast host turned surrogate, Mary B., for an intimate, at-home conversation on the topic of CONSCIOUS PARENTING. In honor of Mother's Day 2024, Tony takes the interviewer's seat and talks to both Sage and Mary about the principles, strategies, tools, and learnings derived from their own journey as mothers. This enlightening conversation transcends traditional notions of parenting, as the trio explores the complexities of modern family dynamics. From blended families, stepparents, same-sex relationships, and co-parenting arrangements, Tony, Sage, and Mary discuss tips for how to make it work on the evolving landscape that is parenthood today. One of the highlights of this conversation is their working definition of MODERN CONSCIOUS PARENTING -- the shift from stress and fear-based parenting to an empowering and integrative awareness-based parenting.  The family discuss the helpfulness of evolving from high-resistance parenting towards a more mindful, self-reflecting, and self-aware approach. By prioritizing both presence and connection, they explain how parents can create an environment that nurtures the growth of beautiful little human beings – an inside out job. The three also emphasize the significance of our language choices around children, advocating for curiosity over fury and mindfulness over fear. They also share personal anecdotes from their own experiences as parents, highlighting the impact of screen and other stimulus on children's emotional development, creativity, imagination and worldview. This episode offers invaluable insights for parents, prospective parents, and anyone interested in creating meaningful connections within their families. By embracing conscious parenting practices, Tony, Sage, and Mary invite listeners to embark on a journey of personal growth, self-discovery, and lasting harmony. Join us as we explore the transformative power of intentional parenting and discover how a slight shift in our focus can lead to profound changes with children and within ourselves! To watch this episode, you can go to: https://www.youtube.com/watch?v=b-mZ6I6OU-8 SHOW NOTES: 3:58  What is “Conscious Parenting” 6:52  Most parents are in survival 8:16  Genomic imprinting and intention for parents-to-be 11:23  Sage explains their modern family arrangement 13:44  Library Story - the impact of language on kids 17:44  Fiji happiness we can all model 17:49  Who's afraid of the dark? (And why) 22:43  Kids want to watch movies over and over and… 24:05  Rudolph Steiner, Waldorf dolls, passive toys/active kids 25:56  Mary B's galloping on straws story 27:09  Children's autonomy and decision making 31:05  Magda Gerber's respectful parenting 31:40  How to handle kids' big waves of emotion 33:14  Mary B's Parenting Hack: Broccoli or Mac-N-Cheese Game 35:47  Esther Perel's 7 Verbs that shape Intimacy 37:44  A wave has a beginning and an end 38:28  Dadda Tony Story: Context is everything 41:15  Read the Room 44:18  Disneyland Dads and dynamics of parenting partners 46:55  Card of the Week: Don't cave to her demands! 49:20   Becoming parents later in life 52:44  Daddy/Father and Mommy/Mother 57:41  Tony's disappearing thumb 59:40  Profound Knowledge: Set each other up to win 1:00:48  Mary B on The Terrible Twos 1:02:48  Sage on How To Apologize (after I trip her, or bump her, or…) 1:05:15  Captain and Co-Captain 1:06:44  Dial-in affection aggression (because they're so cute!) 1:08:25  Giving hierarchy to elders and combatting The Pleaser 1:12:12  Tony's Summary: Conscious Parenting Principles 1:15:20  Sage's Summary: The Dance of Parenting DELETED SCENES AND OUTTAKES: 1:21:20  #1  Story of Tony's 64th Birthday dinner, The Super Silly Tango on the potty, Polaroid pictures, and our ancestors 1:25:09 #2  Center yourself first. Especially when “stuff came out of her mouth” 1:32:03 #3  More on last night 1:33:26 #4  Led Zepplin and becoming our parents 1:33:55 #5  Babytalk, bright lights and big screens 1:34:44 #6  The Noticing Game 1:35:52 #7  “Dadda's a nakey baby!”

In this episode, Heather E. Williams, PhD, MBA, MS, PgD, ErCLG, CG (ASCP) MB, the Chief Operating Officer of Cache DNA, chats about her career journey and the importance of always learning. Heather's passion for medicine and genetics has led her from childhood dreams of being like Dr. Quinn, Medicine Woman to training as a clinical laboratory geneticist and eventually becoming a COO. She talks about the value of making connections, grabbing every chance to learn, and how genetic results can really make a difference in patient care. Tune in to hear more about Heather's career story and get a sneak peek into what she does at Cache DNA.Link In with HeatherCache DNAConnect with us!Link In with CarinaLink In with AlisonCheck out our three most downloaded episodes:Applying the Flagship “What If” Approach to Talent Acquisition With Leslie Martin, VP of Talent Acquisition at Flagship PioneeringA Biotech Built on Culture & Community with Adam Thomas, Chief People Officer at SynlogicIngraining Diversity into the Business Bloodline with Tiffany Summerville at Sherlock BiosciencesSubscribe here:AppleSpotifyGoogle PodcastRSS feedLearn more about Recruitomics ConsultingCheck out our reading listDownload our free startup resources guide to grow your biotech efficientlyIf you're on the job market, visit the Collaboratory Career Hub

News items read by Laura Kennedy include: 18th Century cleft palate prosthesis found in mouth of Polish crypt skeleton (details)(details)(details) Excavations off Great Barrier Reef prove early Aboriginal Australians crafted pottery (details)(details) Analysis of pyramid damage suggests Teotihuacan suffered through five damaging earthquakes (details)(details) Genomic study proves Blackfoot Confederacy historical rights with lineage tracing to Late Pleistocene (details)(details)

ONCE UPON A GENE - EPISODE 221 BeginNGS - Newborn Genomic Sequencing to End the Diagnostic Odyssey with Dr. Stephen Kingsmore, Wendy Erler and Tom DeFay I'm joined by Dr. Stephen Kingsmore, Wendy Erler and Tom DeFay to discuss BeginNGS, a ground-breaking initiative that stands at the forefront of genetic sequencing and rare disease diagnosis.  EPISODE HIGHLIGHTS What led to the creation of BeginNGS? Rare genetic diseases are an immense health ecosystem challenge- receiving a timely diagnosis. On average, it takes 4.8 years to diagnose a child with a genetic disease, and meanwhile, symptoms continue to worsen and the disease progresses. The goal of BeginNGS is to prevent or reduce the impact on children with rare genetic diseases, minimizing suffering, cost and delay of diagnosis.  Why is BeginNGS an important initiative to support? Anyone connected to the rare disease community shares the same vision for a world where every rare disease patient receives the right effective treatment at the right time. That starts with changing the diagnostic odyssey and ensuring early, fast diagnosis. What is the mission of the BeginNGS Consortium? The BeginNGS Consortium is a partnership of pharmaceutical and biotech companies, sharing a vision of the right effective treatment at the right time. Our vision is ultimately to ensure every baby born in the United States has the opportunity to be screened for rare disorders. What differentiates this program and the consortium is that the patient communities have been represented from the beginning and the patient population communities has been impressive. Some of our working groups are led by members of the patient community to make sure that what's delivered is valuable to the patients.  What are the major pain points to leveraging newborn screening for preventable disorders and broad use of rapid diagnostic genome sequencing? Pediatricians rarely order genome sequencing. We estimate only 2% of children who need the testing get it. Additionally, even when testing is ordered, it doesn't always translate into optimal treatments and there can still be delays in life-saving treatments.  What does the future look like for BeginNGS? The BeginNGS Consortium is comprised of rare disease advocacy organizations, parent support groups, healthcare systems, policy makers, experts in academic medicine, biotech companies developing new genome sequencing methods and pharmaceutical companies developing new treatments for rare genetic diseases. We hope to increase the size of the consortium so we can grow the organization and capture every voice and represent every genetic disease. Another strong aspiration is to raise grant support and funding to complete and deploy our pivotal clinical trial.  LINKS AND RESOURCES MENTIONED BeginNGS https://radygenomics.org/begin-ngs-newborn-sequencing/ Alexion https://alexion.com/ ONCE UPON A GENE - EPISODE 213 - Finding Strength In Every Step https://effieparks.com/podcast/episode-213-finding-strength-in-every-step Frontiers 2024 Conference https://radygenomics.org/frontiers-conference/ CONNECT WITH EFFIE PARKS Website https://effieparks.com/ Twitter https://twitter.com/OnceUponAGene Instagram https://www.instagram.com/onceuponagene.podcast/?hl=en Built Ford Tough Facebook Group https://www.facebook.com/groups/1877643259173346/