DNA molecule containing genetic material of a cell
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3 episodes with chromosomal
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2 episodes with chromosomal
2 episodes with chromosomal
4 episodes with chromosomal
3 episodes with chromosomal
3 episodes with chromosomal
2 episodes with chromosomal
2 episodes with chromosomal
Chromosomal recombination is an essential part of the life cycle of all sexually reproducing organisms. Yet, the system is complex, involving hundreds to thousands of proteins and RNAs. It also involves DNA repair pathways, which are themselves incredibly complex. The newest available information on recombination tells us it is mutagenic, meaning that recombination erodes the very places where recombination happens. How did such a system arise by chance? Can we assume the recombination rate has always been the same? What happens when a new allele arises in the protein that controls recombination? What is the mutation burden caused by this important system? Finally, how does this affect the creation-evolution debate? Links and notes: 15 Questions for evolutionists, #8 How did sex originate? Geeking out about DNA damage repair, June 2023. Grey et al. 2018 PRDM9, a driver of the genetic map, PLoS Genet 14(8):e1007479. Altemose et al. 2017 A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis, eLife 6:e28383. Robert Carter gets everything wrong?, creation.com, 10 Jul 2021. Hussin et al. 2011 Age-dependent recombination rates in human pedigrees, PloS Genetics 7(9):e1002251. Wang et al. 2012 Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm, Cell 150(2):402–12. African origins and the rise of carnivory, creation.com,19 Dec 2020. Hinch, A.G. et al., The landscape of recombination in African Americans, Nature 476:170–177, 2011. Hinch et al. 2023 Meiotic DNA breaks drive multifaceted mutagenesis in the human germ line, Science 382:eadh2531.
In this eye-opening episode of "Taco Bout Fertility Tuesday," we delve into the complex world of chromosomal issues in pregnancy and how risk factors change as women age. From understanding the statistical odds to exploring diagnostic tests, we unravel the science in a way that's easy to digest. Join us as we dissect the facts, and offer a helping hand through the journey of reproductive health.
In this episode, we review the high-yield topic of Chromosomal Structure from the Biochemistry section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message
References Nature. 2020 Jun; 582(7813): 577–581 Science Immunology 2018.26 Jan Vol 3, Issue 1 --- 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
The Christian Outlook – September 2, 2023 Scott Furrow and Erik Baptist, senior counsel for Alliance Defending Freedom, discuss the legal challenges against the FDA's approval and distribution of the abortion pill, as well as the ethical concerns, and safety issues surrounding it. Scott Furrow and Nicole Hunt of Focus on the Family talk about the abortion industry's opposition to legislation supporting alternatives to abortion and women's choices for life. Despite claiming to be pro-choice, the industry resists measures that don't align with their profit-driven focus, as seen in examples from Colorado and California. Brian From and Aubrey Sampson invite Michael Graham to discuss his co-authored book, The Great Dechurching: Who's Leaving, Why Are They Going, and What Will It Take to Bring Them Back? Georgene Rice talks with Heidi St. John, a homeschool mom of seven, a podcaster, and author of MomStrong 365: A Daily Devotional to Encourage and Empower Everyday Moms., about how everyone has a unique role to play in fulfilling God's purposes, in this time and season in their life. John Hall and Kathy Emmons talk with Grant Horner, a professor at the Master's University in Santa Clarita, California, about how the transgender movement is attempting to erase the way God has designed humanity.See omnystudio.com/listener for privacy information.
Virginie Courtier-OrgogozoBiodiversité et écosystèmes (2022-2023)Collège de FranceColloque - Integrating Evolutionary Genetics and Ecology : How Do Genomic Architecture and Ecological Processes Interplay during Evolution? The Example of Chromosomal Inversions in Seaweed FliesClaire Mérot, université de Rennes, Rennes, France
Human pluripotent stem cells have an unlimited capacity to self-renew in culture. This feature, along with their ability to become any cell type in the adult body, makes them a unique tool to study human biology in health and disease. Unfortunately, human pluripotent stem cells have a propensity to acquire genetic abnormalities in culture that may limit their scientific and clinical use.Among the most prevalent genomic changes found in pluripotent stem cells are various forms of over-representation of sequences on the long arm of chromosome 20, with up to 20% of tested cultures containing such an aberration. One such anomaly, the isochromosome 20 mutation, is also found in amniocentesis analyses. In this episode, Martin Pera is joined by three scientists, who along with their colleagues, authored the recent paper published in Stem Cell Reports entitled, The isochromosome 20q abnormality of pluripotent cells interrupts germ layers differentiation. This publication explores the effects of this particular anomaly on the ability of pluripotent stem cells to differentiate both spontaneously and by directed differentiation. The results were surprising, with implications for understanding early development and the potential therapeutic use of pluripotent stem cells. The authors also discuss some of the challenges of working with pluripotent stem cells. GuestsIvana Barbaric, PhD, University of Sheffield, UK Pete Coffey, PhD, University College London and the University of California, Santa Barbara, US Loriana Vitillo, PhD, University College London, UKHostMartin Pera, PhD, Editor-in-Chief, Stem Cell Reports and The Jackson LaboratoryTwitter: @martinperaJAXSupporting ContentThe isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation, Vitillo, et. al., Stem Cell Reports (2023)About Stem Cell ReportsStem Cell Reports is the open access journal of the ISSCR for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Twitter: @StemCellReportsAbout ISSCRWith more than 4,600 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.ISSCR StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsJack Mosher, Scientific AdvisorVoice WorkBen Snitkoff
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.02.530628v1?rss=1 Authors: Schenkel, L., Wang, X., Le, N., Burger, M., Kroschewski, R. Abstract: In eukaryotes, chromosomes are wrapped in an endoplasmic reticulum (ER)-derived envelope to form the nucleus. Whether any DNA, or only chromosomes, can be enveloped in this way is unclear. Live-cell imaging revealed that DNA transfected into mammalian cells was either captured directly in the cytoplasm, or if it entered the nucleus was soon expelled from it. In the cytoplasm, plasmid DNA was rapidly surrounded by an ER-derived double membrane and frequently colocalized with extra-chromosomal DNA of telomeric origin expelled from the nucleus. Therefore, this structure was termed exclusome. Exclusome membranes contain the inner-nuclear membrane proteins Lap2{beta} and Emerin but differ from the nuclear envelope by the absence of the Lamin B Receptor, nuclear pore complexes (NPCs) and by the presence of fenestrations. Strikingly, Emerin was strongly enriched at exclusomes and overexpression of its LAP2, Emerin, MAN1 (LEM)-domain reduced cells with exclusomes. Together, cells wrap chromosomes and two types of extra-chromosomal DNA into similar yet distinct envelopes. Thereby, they distinguish, sort, cluster, package, and keep chromosomal and extra-chromosomal DNA apart in the nucleus and the exclusome, respectively. We suggest that while all DNA molecules are enveloped through virtually identical mechanisms, only chromosomes somehow promote NPC assembly to form a nuclear envelope. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
(00:31) Could you provide a little bit about yourself and your background? (02:04) Could you provide an overview of the chromosomal microarray assay? (05:49) Why should the chromosomal microarray assay be used over other available assays, such as FISH? (08:56) Does the chromosomal microarray provide good benefits in terms of gain of 7 and loss of 10, and EGFR amplification? (12:03) What's the value of utilizing the test alongside a neuro-specific NGS panel, such as Mayo Clinic Laboratories' NONCP panel? (17:20) How are the results used in patient care? (19:41)Is there anything else you feel it's important to highlight?
Eric Hovind's Creation Today delves into the science of our common ancestors -- the so-called Adam and Eve -- as traced back through our y-chromosomes and our mitochondrial DNA. Dr. Robert Carter guests to give us an estimate of when they lived... does it line up with the young-earth Biblical creation narrative?Using gene sequencing, one can begin to trace backwards to common male ancestors of populations and back far enough to an individual known as the “Y-chromosomal most recent common ancestor”. This individual is also informally called “Y-chromosomal Adam”, invoking the idea of the character Adam from the Bible, but that colloquialism leads to some unfortunate misconceptions.An interesting feature of mitochondria is that is has its own DNA, which is entirely separate from the DNA in the nucleus of cell. While that nuclear DNA is a combination of the mother and father, the mitochondrial DNA comes exclusively from the mother. Since there is no blending of mitochondrial DNA, any variations from mother to child can come from only one source – genetic mutations. As such, it's possible to track the matrilineal most common ancestor. Just like Y- chromosomal Adam, mitochondrial Eve would be the most recent common female ancestor, and would have been one of a larger population.Creation Today Season 5 Episode 6 - https://www.youtube.com/watch?v=pcuMIATlHGEFollow me athttp://www.twitter.com/paulogia0http://www.facebook.com/paulogia0Support the show
Coming in hot for this November month! Today we have with us Dr. Vaughn Cooper, professor and director of the Center for Evolutionary Biology and Medicine at the University of Pittsburgh. Tune in to learn about his deep love for evolution, his background at the Lenski lab, and his current work studying biofilms. For the news section, we first bring you Jenny's recent paper looking at the evolution of resistance to tigecycline and then move on to a UAC paper on the evolution of chromosomal hybrids which result in enlarged chromosomes. For a change, this time we also talk about vaccines, covering a surveillance study looking at the effect of pneumococcal vaccines and COVID-19 on AMR. We finish up the news by mentioning two big things released this month: a follow-up to the report on the global burden of AMR in 2019, this time with numbers on the WHO European Region, and a new WHO Fungal Priority Pathogen List. Buckle up, this episode covers a lot! Check relevant links in the show notes at www.uac.uu.se/the-amr-studio/episode43/. Follow our updates on Twitter on www.twitter.com/uac_uu with #theAMRstudio hashtag! Theme music by Henrik Niss: www.tinyurl.com/henriknissspotify.
Trigger warning: In this episode, our guest shares her journey with the loss of her unborn daughter. If you or someone you love has recently experienced a miscarriage or the tragic loss of a child, please feel free to skip this episode during your healing process. We have 80+ other powerful conversations to enjoy at www.warriorsunmasked.com Welcome back to another episode of Warriors Unmasked! Today while Clint is out changing the world, Chuck sits down with author, mother, and woman of extraordinary faith, April Fore. April will take a deep dive into her journey from living a fun life as a nanny to finding out she was expecting a child of her own. It wasn't long after the exciting news that April found herself at the Doctors office for a routine checkup where she would learn her future daughter had Turner Syndrome. (A Chromosomal disorder in which a female is partially or completely missing an X chromosome) This devastating diagnosis would ultimately result in the loss of her unborn daughter… However, the story does not end there. Through the power of prayer, her faith in God the creator, and the understanding that all things, even the deepest pain of losing a child could result in a beautiful testimony if she did not give up and stay in her pain and depression. Hit play to hear the exact steps April took to turn her tragedy into a testimony, how you can help spread awareness of Turner Syndrome, practical ways to heal and build your faith and so much more! To learn more about April, and how her daughter's legacy is changing lives all over the world, or to connect with us follow the links below! More Of What's Inside: How April managed her anger with God Finding the good in any situation The true power of prayer Pain can have a beautiful purpose We are all God's children Turner Syndrome Awareness Letting others have their own healing journey A look into April's next book Have faith even if it looks bad And much more! GUEST LINKS: https://www.instagram.com/theeggstories http://facebook.com/theadventuresofegg What Is Turner Syndrome? - Turner Syndrome Foundation LINKS: malarchuk.com/book malarchuk.com www.thecompassionateconnection.com www.warriorsunmasked.com Follow us on Instagram Like us on Facebook Subscribe To Our YouTube My Community Contact Episode Minute By Minute: 0:02 A look into today's episode 1:28 Thank you to today's sponsors 2:24 Get to know April Fore 5:26 When April heard the diagnosis 12:23 The importance of staying active 21:00 Handling life after the loss of a child 26:16 Overcoming depression and bad coping habits 33:00 We are all perfect just the way we are 37:33 How April learned to love after loss 44:55 The importance of feeling your feelings
References Mechanisms of Ageing and Development.2006. Volume 127, Issue 9, Pages 705-718 J Bioenerg Biomembr. 2015 April ; 47(1-2): 173–188 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
$5 Q-BANK: https://www.patreon.com/highyieldfamilymedicine Aneuploidy, Robertsonian translocation, mosaicism, prenatal screening, physical exam findings, Down's syndrome, Edward's syndrome, Patau syndrome, Klinefelter syndrome, Turner syndrome, Triple X syndrome, XYY syndrome, Cri Du Chat syndrome, Wolf-Hirschhorn syndrome, Jacobsen and Paris-Troussaeu syndromes, Charcot-Marie-Tooth syndrome, Prader-Willi and Angelman syndromes, trinucleotide repeat disorders, Fragile X syndrome, Huntington Disease, Myotonic dystrophy Type I, spinocerebellar ataxia, and Friedrich ataxia.
Dr. Shannon M. Clark discusses the following with genetic counselor, Liz Sheehan @agirlsnameisbizbiz: •what are fetal chromosomal aneuploidies •different types of antenatal screening tests •cell-free DNA screening •NT measurement plus serum screening in first trimester •quad screen in second trimester •screening PGT tested embryos •ultrasound soft markers: choroid plexus cysts, echogenic intracardiac focus, echogenic bowel, pylectasis, single umbilical artery --- Support this podcast: https://anchor.fm/adoctordeliverspodcast/support
Hello everyone in this episode I will be talking about living life with chromosomal abnormalities and how it affects me and so much more etc --- Send in a voice message: https://anchor.fm/wondergirlsaida/message
Professor Simon Fishel is the Founder, President, and Head of R&D at CARE Fertility in the UK. CARE is celebrating its 20th anniversary and apparently, a CARE baby is delivered every 4hours! Simon's early works were as Deputy Scientific Director of the world's first ‘test-tube baby clinic' at Bourn Hall, Cambridge, the first to demonstrate that embryos are capable of responding to their environment and communicating with the uterus and external factors. In our chat, we discuss what this means. Simon was also the first to show that the human embryo in vitro synthesizes and secretes the pregnancy hormone HCG (Science, 1984), and early in the 1990's he was the first to demonstrate conclusively the need to permanently immobilize the sperm tail for efficient and successful ICSI in humans, and during the late 1980s and early 1990's he pioneered human sperm microinjection. We discussed the efficiency of the endometrial scratch as well as eating pineapple post embryo transfer. Simon also gave his views on studies regarding Vitamin B3 and its impact on preventing miscarriage. One, in particular, was in Australia, where scientists identified a major cause of miscarriages and multiple birth defects that could change the way women prepare for pregnancy. Having low levels of a vital molecule called Nicotinamide Adenine Dinucleotide (NAD) damages embryos in the crucial first weeks of pregnancy when organs start forming, the scientists at Victor Chang Cardiac Research Institute have discovered. Simon has said - “While an intriguing and potentially important scientific study, which has been well conducted, it must be recognized that miscarriage has many causes.” In our chat, Simon discusses CARE's research which has shown a Male Marker for miscarriage and explained the blood test that could be carried out to determine whether a couple is carrying the marker. We also discussed the mental health aspect of failed fertility treatment and Simon gave his views on the postcode lottery in the UK, as well as how he feels IVF is looking in its 40th year of existence. It was interesting to hear him say " I have a great sadness that in the country that created IVF and made it available to the world that we still can't have a single unified policy" To follow Simon on Twitter visit I also referred to a previous episode I had released where I had covered the impact of fertility treatment on mental health, with blogger Strength and Infertility which you can visit here Don't forget to join my closed Facebook group Plus if you don't mind helping me out, a quick review on iTunes and clicking subscribe to this podcast would be AMAZING... just click here
TEACHING CARE 1-TO-1 ONLINE TUITION AND COACHING CLASSES by top teachers of India
Please see You Tube Video here for Chromosomal Mutations - NEET BIOLOGY For more free online class videos, you can visit our You Tube Channel here Teaching Care provides Online classes by best teachers; online tuition classes, online tutors and live 1-to-1 coaching classes for CBSE, ICSE, IGCSE, IB, state boards, NTSE, Olympiads, JEE and NEET. Best tutorials for English, Mathematics, Science, Physics, Chemistry, Biology, Coding Classes, Computer Science, Accountancy, Business Studies, Economics, Hindi, Engineering etc for class 4th to class 12th to UG & PG levels. Book free trial class at Teaching Care or Call +91-9811000616, +91-9821126195 or Sign Up here for free demo class or email us at hr@teachingcare.com --- Send in a voice message: https://anchor.fm/teachingcare/message
TEACHING CARE 1-TO-1 ONLINE TUITION AND COACHING CLASSES by top teachers of India
Please see You Tube Video here for Chromosomal Mutations - NEET BIOLOGY For more free online class videos, you can visit our You Tube Channel here Teaching Care provides Online classes by best teachers; online tuition classes, online tutors and live 1-to-1 coaching classes for CBSE, ICSE, IGCSE, IB, state boards, NTSE, Olympiads, JEE and NEET. Best tutorials for English, Mathematics, Science, Physics, Chemistry, Biology, Coding Classes, Computer Science, Accountancy, Business Studies, Economics, Hindi, Engineering etc for class 4th to class 12th to UG & PG levels. Book free trial class at Teaching Care or Call +91-9811000616, +91-9821126195 or Sign Up here for free demo class or email us at hr@teachingcare.com --- Send in a voice message: https://anchor.fm/teachingcare/message
Kelly is a mum of four. She has two living children – Brooklyn and Jake, and two children who she had to say goodbye to within hours of them being born – Nina and Molly.Kelly learned in her early life that she was a carrier of a Chromosomal issue running in the family, passed down from her dad. She is a carrier but when she has children they could either be totally fine, a carrier like her, or incompatible with life, ending in miscarriage, stillbirth or death shortly after birth. A 50 % chance of her baby not surviving.Her first three attempts to have a baby ended in miscarriage but after that she went on to have two healthy children. They are both carriers too but healthy in themselves.After this, Kelly just didn't feel that he family was finished and she desired to have another baby. So she and her husband tried again.They became pregnant but the CVS results at 14 weeks showed that this baby was affected and was incompatible with life. They had to make decisions around terminating the baby or carrying to term.They chose to carry their baby to term and with the help of a supportive team she was born at 36 weeks, alive and with her eyes open. She lived for 1 hour and 46 minutes. Her name is Nina.After this experience of losing Nina the feelings of wanting to try for another child just wouldn't go away. Her husband was not on board with her but in the end they did try again and Kelly became pregnant again and the CVS results showed that this baby also was not compatible with life.They gave this baby what they gave Nina. Kelly carried her to term in the hopes of also meeting her alive. She was born alive at 36 weeks and lived for 1 hour and 30 minutes. Her name is Molly.Kelly shares with us the isolation, the grief and the heartache she and her family have been through but also how they are doing well now and she finally feels herself again.Connect with Kelly: Instagram -https://www.instagram.com/thegriefdebrief/Blog - https://eitsirhc.wixsite.com/bestillandknowkcConnect with Janine:Instagram - https://www.instagram.com/waitingforyou.podcast/Janine's photography instagram - https://www.instagram.com/janinefoxphotography/Share your story on the podcast - https://www.janinefoxphotography.co.nz/podcastMusic written and recorded by Alan Meharry and Stu Fox
Emily, a self-professed “Chemical Queen”, shares her fertility journey over the last four years, in which she has been pregnant seven times. Emily has a chromosome abnormality called "Robertsonian Translocation" of chromosomes 14 and 22 which puts her at higher risk of early miscarriage but following 4 chemical pregnancies she finally found a team who looked further. After putting her on a variety of medications to support her hormones around the start of her pregnancies, one stuck! Emily is trying again for number 2 and devastatingly, has had another 2 miscarriages. This story has all the feels.Episode notes:Bulk billed IVF clinic: https://www.adorafertility.com.au/Join me on Instagram: @wombroom.podcastIf you're enjoying the show please leave a review! Takes a mere few minutes and will help get these stories into more ears that really need them.You can listen to host Laksmi Wilson's story here:https://podcasts.apple.com/au/podcast/why-does-this-keep-happening-recurrent-miscarriages/id1484930949?i=1000528572349Support the show (https://www.patreon.com/wombroom)
Evaluation and Credit: https://www.surveymonkey.com/r/MedChat32 Target Audience This activity is targeted toward primary care and oncology specialties. Statement of Need According the National Human Genome Research Institute, genomic factors play a role in nine of the ten leading causes of death in the U.S.; e.g. heart disease, cancer and diabetes. If providers have a better understanding of genomic testing and applications, it can result in earlier diagnosis, interventions and targeted treatments for specific diseases, improving overall patient outcomes. Objectives At the conclusion of this offering, the participant will be able to: Differentiate between genetic and genomic testing. Describe the essentials of genomic testing. Define key applications in clinical medicine where genomic testing is utilized: constitutional, oncology and microbiological. Moderator Steve Patton, D.O. Family Medicine Norton Community Medical Associates Speaker Charles Myers, D.O. Clinical and Laboratory Pathology Norton Medical Group Moderator and Planner Disclosures The moderator, speakers and planners for this activity have no relevant relationships to disclose. Commercial Support There was no commercial support for this activity. Physician Credits American Medical Association Accreditation Norton Healthcare is accredited by the Kentucky Medical Association to provide continuing medical education for physicians. Designation Norton Healthcare designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Resources for Additional Study Candida auris: Diagnostic Challenges and Emerging Opportunities for the Clinical Microbiology Laboratory https://pubmed.ncbi.nlm.nih.gov/34178208/ Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG) https://pubmed.ncbi.nlm.nih.gov/34131312/ Norton Healthcare, a not for profit health care system, is a leader in serving adult and pediatric patients throughout Greater Louisville, Southern Indiana, the commonwealth of Kentucky and beyond.. Five Louisville hospitals provide inpatient and outpatient general care as well as specialty care including heart, neuroscience, cancer, orthopedic, women's and pediatric services. A strong research program provides access to clinical trials in a multitude of areas. More information about Norton Healthcare is available at NortonHealthcare.com. Date of Original Release |October 2021 Course Termination Date | October 2023 Contact Information | Center for Continuing Medical, Provider and Nursing Education; (502) 446-5955 or cme@nortonhealthcare.org
Welcome to My AP Biology Thoughts podcast, my name is Stefanie Ribecca and I am your host for episode # 104 called Unit 5 Heredity: Chromosomal Inheritance. Today we will be discussing how inheritance occurs in the chromosomal level. Segment 1: Introduction to Chromosomal InheritanceChromosomal inheritance is an extension of Mendelian genetics. Chromosomes contain DNA which carry the genetic information that code for proteins. Chromosomes are found in pairs, and increase genetic variation during meiosis. Segment 2: More About Chromosomal InheritanceDuring meiosis, non sister chromatids in homologous pairs exchange information during crossing over. Certain genes may be close together on the chromosome and may appear to be inherited together. Segment 3: Connection to the CourseChromosomal inheritance allows for a combination of traits from both parents. Genetic diversity from chromosomal inheritance allows individuals in a population to adapt to the environment. Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com). Music Credits:"Ice Flow" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/ Subscribe to our Podcasthttps://podcasts.apple.com/us/podcast/my-ap-biology-thoughts/id1549942575 (Apple Podcasts) https://open.spotify.com/show/1nH8Ft9c9f6dmo75V9imCk (Spotify) https://podcasts.google.com/search/my%20ap%20biology%20thoughts (Google Podcasts ) https://www.youtube.com/channel/UC07e_nBHLyc_nyvjF6z-DVg (YouTube) Connect with us on Social MediaTwitterhttps://twitter.com/thehvspn ( )https://twitter.com/thehvspn (@thehvspn)
Research and articles, I've attached to my Twitter page, regarding chromosomes 11 and 3 in relation to alcoholism, depression and suicidality. Possibly relates to successive bubonic plagues in 1625 and 1665. --- Send in a voice message: https://anchor.fm/benjamin-allen-belzer/message Support this podcast: https://anchor.fm/benjamin-allen-belzer/support
In this episode, we review the high-yield topic of Chromosomal Diseases from the Biochemistry section. --- Send in a voice message: https://anchor.fm/medbulletsstep1/message
This episode covers chromosomal translocations!
Compare the causes, processes and effects of different types of mutation, including but not limited to: - point mutation - chromosomal mutation Distinguish between somatic mutations and germ-line mutations and their effect on an organism. Thanks to STEM Reactor for sponsoring this podcast. They provide everything you need to do biotechnology at school, check them out at www.stemreactor.com.au
Practice Bulletins #226 - Published October 2020 1. Cell-free DNA screening has the best sensitivity and specificity of all screening methods. But before you order it, it's best to get a prenatal ultrasound 2. Best non-cell-free screening modality is the sequential integrated serum screen (1st-tri serum + NT ultrasound + 2nd-tri serum) 3. Formal anatomy survey should be offered at 18 - 22 wga; can identify soft markers for T21 and T18 4. Prenatal genetic screening should be offered to all pregnant women regardless of risk profile 5. Anything that doesn't add up, it's best to just refer to a genetics counselor or even your friendly MFM for clarification. Show Notes Wine pairing: 2017 Garnacha from Las Rocas Theme music by Evan Handyside Logo design by JD Dotson (jddotson1@gmail.com)
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.390930v1?rss=1 Authors: Das Roy, R., Hallikas, O., Christensen, M. M., Renvoise, E., Jernvall, J. Abstract: Exploration of genetically modified organisms, developmental processes, diseases or responses to various treatments require accurate measurement of changes in gene expression. This can be done for thousands of genes using high throughput technologies such as microarray and RNAseq. However, identification of differentially expressed (DE) genes poses technical challenges due to limited sample size, few replicates, or simply very small changes in expression levels. Consequently, several methods have been developed to determine DE genes, such as Limma, RankProd, SAM, and DeSeq2. These methods identify DE genes based on the expression levels alone. As genomic co-localization of genes is generally not linked to co-expression, we deduced that DE genes could be detected with the help of genes from chromosomal neighbourhood. Here, we present a new method, DELocal, which identifies DE genes by comparing their expression changes to changes in adjacent genes in their chromosomal regions. Our results show that DELocal provides distinct benefits in the identification of DE genes. Furthermore, our comparative analysis of the dispersal of genes with related functions suggests that DELocal is applicable to a wide range of developmental systems. With increasing availability of genomic data, gene neighbourhood can become a powerful tool to detect differential expression. Copy rights belong to original authors. Visit the link for more info
In this week’s episode I chat to Nadia about her three births including her most recent; a maternal-assisted cesarean. Nadia’s first son, a boy named Pio, was diagnosed with a rare chromosomal abnormality and was born via cesarean at 20weeks. She discusses her disbelief at the diagnosis and the subsequent grief of her loss followed by the healing arrival of her rainbow baby, Riviera. Nadia found her mothering groove when Riviera was six-months-old so the last thing she expected was to fall pregnant again. Her second daughter, Florencia, was born in the middle of Melbourne’s Covid lockdown but despite restrictions, she was delighted to have the opportunity to experience a natural cesarean and admits that the bond and connection was instant.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.06.328039v1?rss=1 Authors: Prost, J. A., Cameron, C. J., Blanchette, M. Abstract: Genomic organization is critical for proper gene regulation and based on a hierarchical model, where chromosomes are segmented into megabase-sized, cell-type-specific transcriptionally active (A) and inactive (B) compartments. Here, we describe SACSANN, a machine learning pipeline consisting of stacked artificial neural networks that predicts compartment annotation solely from genomic sequence-based features such as predicted transcription factor binding sites and transposable elements. SACSANN provides accurate and cell-type specific compartment predictions, while identifying key genomic sequence determinants that associate with A/B compartments. Models are shown to be largely transferable across analogous human and mouse cell types. By enabling the study of chromosome compartmentalization in species for which no Hi-C data is available, SACSANN paves the way toward the study of 3D genome evolution. SACSANN is publicly available on GitHub: https://github.com/BlanchetteLab/SACSANN Copy rights belong to original authors. Visit the link for more info
** Thanks for downloading this episode. If you'd like to stay in touch with our continuing story, Season 2 continues at This Medical Life, in which Dr Travis Brown continues his exploration of diseases and our approaches to treatment from history to the modern day. Have a look in your podcast app now for This Medical Life, and hit subscribe so you never miss an episode ** Chromosomal abnormalities are often incompatible with life. However, there are a few exceptions to this rule and history has shown us that certain paired chromosomes can include a third. These conditions are known today as Down syndrome (Trisomy 21), Edwards' syndrome (Trisomy 18) and Patau syndrome (Trisomy 13). These syndromes are routinely screen for in pregnancy with NIPT (Non-Invasive Prenatal Testing). This podcast includes an interview discussing the application of NIPT with Professor Graeme Suthers and the path ahead for foetal screening and this section of the podcast is eligible for 1 RACGP CPD point – self reporting. Professor Graeme SuthersBSc (Med), MBBS, PhD, FRACP, FRCPA, GAICDclinpath.com.au/about-us/clinpath-leadership/our-pathologists/professor-graeme-suthers/ This Pathological Life is produced by Clinpath Pathology in South Australia.See omnystudio.com/listener for privacy information.
Chromosomal abnormalities are often incompatible with life. However, there are a few exceptions to this rule and history has shown us that certain paired chromosomes can include a third. These conditions are known today as Down syndrome (Trisomy 21), Edwards' syndrome (Trisomy 18) and Patau syndrome (Trisomy 13). These syndromes are routinely screen for in pregnancy with NIPT (Non-Invasive Prenatal Testing). This podcast includes an interview discussing the application of NIPT with Professor Graeme Suthers and the path ahead for foetal screening and this section of the podcast is eligible for 1 RACGP CPD point – self reporting. Professor Graeme Suthers BSc (Med), MBBS, PhD, FRACP, FRCPA, GAICD clinpath.com.au/about-us/clinpath-leadership/our-pathologists/professor-graeme-suthers/ This Pathological Life is produced by Clinpath Pathology in South Australia. See omnystudio.com/listener for privacy information.
Today’s episode will inspire you yet again! I chat to Natalie Masson, a woman like you and I who struggled to get pregnant, and against the odds of being 45, with low AMH and high FSH and much more, managed to get pregnant naturally and now has a beautiful family she has always wished for. Natalie doesn’t have Endometriosis, but she does have an awful lot to share from her experience and is why she then went on to focus on helping women with their fertility struggles. Dr Natalie Masson, PhD is a Psychotherapist & Fertility Coach, and founder of Fertility from the Soul, which is a resource for women who are longing for a child, struggling to conceive, and are interested in exploring natural ways to boost fertility. Natalie draws from the experience of many philosophies and healing modalities from both the East and the West to provide coaching, meditations, affirmations, guidance, and resources for improving fertility naturally from a holistic mind-body perspective. Natalie is based in the USA but works with women all over the world. We had a great conversation and talked about: Natalie’s background as an engineer and psychotherapist Natalie’s fertility journey against all the odds including two devastating miscarriages Cognitive behavioural therapy and mind-body awareness Learning to listen to our bodies through awareness Affirmations when you find yourself obsessing about your cycle Chromosomal abnormalities and improving egg quality Nourishment other than nutrition such as emotional help, spirituality and relationships How scientific evidence is lagging anecdotal evidence infertility Benefits of taking 3 months out to improve egg quality Understanding your energy losses and gains Natalie read some example affirmations Meditations and guided imagery Resources Mentioned: Week by Week Fertility Affirmations: https://www.youtube.com/playlist?list=PLcK63CNsBaOx9oX_FpAEFQx2RQ5DcO2hA Affirmations for Improving Egg Quality and Cultivating Optimal Fertility: https://www.youtube.com/watch?v=wwfRo6c34fY&t=576s Meditations and Guided Imagery: https://www.youtube.com/playlist?list=PLcK63CNsBaOw96kjnfkomAhfGSII0C4PQ Connect with Dr Natalie Masson at: Website: http://www.fertilityfromthesoul.com Facebook: https://www.facebook.com/fertilityfromthesoul You Tube Channel: https://www.youtube.com/channel/UCrJynvX1U5wM2BgSC9csVsA Email: info@fertilityfromthesoul.com Further EndoFertility links and resources: Join my Endo Fertility community! Find us in the Thrive and Conceive with Endometriosis Facebook Group. The Endo Fertility Specialist website: https://www.endofertilityspecialist.com Follow me on Instagram (@endofertilityspecialist) and Facebook (@endofertilityspecialist) Intro/Outro Music Credits: Optimistic Future This episode is sponsored by the Endo Fertility Resource Library where you can get your 3 amazing freebies: E-Book: 5 Things I Learnt to Drop My Pain & Optimise My Fertility, Your Guide to Super Sperm, and 88 Ways I Dropped My Pain and Got Pregnant. Make sure you hit SUBSCRIBE so you don’t miss out on any future episodes – which will be out weekly on Wednesdays! And, if you enjoyed this episode, please leave me a rating and a review, it will help it reach many more that need help on their Endometriosis and fertility journeys. Thank you! If you want to be on the podcast or have feedback please email: info@endofertilityspecialist.com This podcast is for educational purposes only. The host claims no responsibility to any person or entity for any liability, loss or damage caused or alleged to be caused directly or indirectly as a result of the use, application, or interpretation of the information presented herein.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.24.264747v1?rss=1 Authors: Iakovlev, M., Faravelli, S., Becskei, A. Abstract: Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single cell RNA-seq data with a simple metric. Chromosomal segments and families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.262121v1?rss=1 Authors: Gerak, C. A. N., Cho, S. Y., Kolesnikov, M., Okon, M., Murphy, M. E. P., Sessions, R. B., Roberge, M., McIntosh, L. P. Abstract: ETV6 is an ETS family transcriptional repressor that self-associates by its PNT domain to facilitate cooperative DNA binding. Chromosomal translocations frequently generate constitutively active oncoproteins with the ETV6 PNT domain fused to the kinase domain of one of many protein tyrosine kinases. Although an attractive target for therapeutic intervention, the propensity of the ETV6 PNT domain to polymerize via the tight head-to-tail association of two relatively flat interfaces makes it challenging to identify suitable small molecule inhibitors of this protein-protein interaction. Herein we provide a comprehensive biophysical characterization of the ETV6 PNT domain interaction interfaces to aid future drug discovery efforts and help define the mechanisms by which its self-association mediates transcriptional repression. Using NMR spectroscopy, X-ray crystallography, and molecular dynamics simulations, we demonstrate that ETV6 PNT domain variants with monomerizing mutations adopt very stable helical bundle folds that do not change in conformation upon self-association. Amide hydrogen exchange and surface plasmon resonance-monitored alanine scanning mutagenesis studies identified hot spot regions within the self-association interfaces. These regions include both central hydrophobic residues and flanking salt-bridging residues. Collectively, these studies indicate that small molecules targeted to these hydrophobic or charged regions within the relatively rigid interfaces could potentially serve as orthosteric inhibitors of ETV6 PNT domain polymerization. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.20.258525v1?rss=1 Authors: Gerak, C. A. N., Zhang, S. M., Balgi, A. D., Sadowski, I. J., Sessions, R. B., McIntosh, L. P., Roberge, M. Abstract: ETV6 is an ETS family transcriptional repressor for which head-to-tail polymerization of its PNT domain facilitates cooperative binding to DNA by its ETS domain. Chromosomal translocations frequently fuse the ETV6 PNT domain to one of several protein tyrosine kinases. The resulting chimeric oncoproteins undergo ligand-independent self-association, autophosphorylation, and aberrant stimulation of downstream signaling pathways leading to a variety of cancers. Currently, no small molecules inhibitors of ETV6 PNT domain polymerization are known and no assays targeting PNT domain polymerization have been described. In this study, we developed complementary experimental and computational approaches for identifying such inhibitory compounds. One mammalian cellular approach utilized a mutant PNT domain heterodimer system covalently attached to split Gaussia luciferase fragments. In this protein fragment complementation assay, inhibition of PNT domain heterodimerization reduces luminescence. A yeast assay took advantage of activation of the reporter HIS3 gene upon heterodimerization of mutant PNT domains fused to DNA-binding and transactivation domains. In this two-hybrid screen, inhibition of PNT domain heterodimerization prevents cell growth in medium lacking histidine. The Bristol University Docking Engine (BUDE) was used to identify virtual ligands from the ZINC8 library predicted to bind the PNT domain polymerization interfaces. Over 75 hits from these three assays were tested by NMR spectroscopy for binding to the purified ETV6 PNT domain. Although none were found to bind, lessons learned from this study may facilitate future approaches for developing therapeutics that act against ETV6 oncoproteins by disrupting PNT domain polymerization. Copy rights belong to original authors. Visit the link for more info
Sexual reproduction increases genetic diversity in Episode 37. Chromosomes are tightly coiled DNA (1:00) and organized in homologous pairs (1:45). The three primary sources of variation within the population are chromosome segregation, independent assortment, and random fertilization (2:15). Do you remember Mendel’s laws? Some chromosomal errors cause genetic disorders (3:20). We can use pedigrees to find patterns in genetic traits (4:20).The Question of the Day asks (5:42) “During what phase of meiosis does crossing over occur? ”Thank you for listening to The APsolute RecAP: Biology Edition!(AP is a registered trademark of the College Board and is not affiliated with The APsolute RecAP. Copyright 2020 - The APsolute RecAP, LLC. All rights reserved.)Website:www.theapsoluterecap.comEMAIL:TheAPsoluteRecAP@gmail.comFollow Us:INSTAGRAMTWITTER
Welcome to another episode of The Hormone Heartbeat Podcast! Today's episode in my fertility series is about miscarriage and understanding what hormonal condition can put you at an increased risk of miscarriage, and what labs you should consider asking your fertility doctor for if you have experienced one or multiple miscarriages. My guest today Dr. Anna D'intino shares her personal experience with miscarriage and how she works with couples on their fertility journey. Dr. Anna D'Intino is a Naturopathic Doctor practicing in Nova Scotia who helps women feel better by optimizing their hormones, supporting them through hormonal challenges and changes and helping them on their fertility journeys. Anna believes that when we are feeling our best, we can achieve anything we want, and she works with her patients to remove their obstacles to health. In today's episode: Introduction from Dr. Anna and her personal experience with miscarriage Language around having a miscarriage and how to talk to love ones Understanding the frequency of miscarriage Defining the different types of miscarriage like chemical pregnancy, spontaneous abortion, blighted ovum The pain of having a miscarriage (in comparison to birth) Explaining the various causes of miscarriage Chromosomal abnormality and miscarriage Predisposing conditions that increase your risk of miscarriage Autoimmune diseases and increased risk Paternal health and its correlation to miscarriage risk Causes of uterine abnormalities Luteal Phase Defect and what to look for in your chart Recommends for staying positive after experiencing 1 miscarriage What to do after you had your first miscarriage What does a fertility workup post-miscarriage look like Top 3 general fertility tips that all couples could benefit from *******Free Gift for Listeners: Guide on How to Support your Fertility Everyday!******* Connect with Guest: Dr. Anna D'intino, ND: Website: www.annadintino.com | Facebook: Dr. Anna D'Intino, ND | Instagram: @annadintino Connect with host: Dr. Antoinette Falco, ND Download your copy of Antoinette's Post-pill Guidebook. Website: www.antoinettefalco.com. Instagram: @drantoinettefalco Please send all inquiries and suggestions, including topics you'd like to see covered on the podcast to thehormoneheartbeatpodcast@gmail.com If you'd like to be a guest on the show and you think you'd be a good fit, please reach out!
Join Matt Hurttado and myself for part 1 of 2 Pathology Review. The following review will be pertaining to the material covered for our 2nd Lecture Exam, which is as follows;Genetic and Chromosomal Disorders- Trisomy 21 (Down Syndrome)- KlineFelter's Syndrome- Turner Syndrome - Autosomal Dominant Vs. Recessive - Sickle Cell Disease Vs. Sickle Cell Trait- Glycogen Vs. Lysosomal Storage Disorders- X-Linked DisordersImmune Disorders- I-IV Hypersensitivity Reactions ( A-llergy C-ytotoxic I-mmune complex D-elayed)- MHC Classes- Heat Shock Proteins- Human Leukocyte Antigen- Crest Syndrome (C-alcinosis Cutis R-aynauds E-sophageal dysmolity S-clerodactyly T-elangiectesia)- Four Phases of Acquired Immunodeficiency Syndrome (AIDS)Reference: Pathology Review (3rd Edition) JR LaRose (For educational/entertainment purposes only, NOT medical advice.)
Cam bravely shares about a chromosomal disorder she was born with that causes female infertility, called Turner Syndrome. This podcast episode is special for two reasons, Cam is the youngest guest to be on the podcast so far. As a member of Gen Z, she is proactively researching her options to grow a family long before she is ready to start one. Interviewing Cam made me realize how much our dialogue around infertility has change over the past decade and how proud I am to be part of this ongoing campaign. Cam was 8 years-old when I started doing this work. That fact and my looming birthday (tomorrow) are making me feel old. More importantly, I'm super proud that conversations like this continue to make a difference for others. Don’t miss Episode 18 of Three Makes Baby Podcast, available on all the podcast platforms.
Today we get to review Non-Mendelian genetics For detailed notes (PowerPoints) visit www.BiologyForBastards.com --- Send in a voice message: https://anchor.fm/bioforbastards/message
Flies and mutations and sex-linked genes, oh my! Different ways things get inherited that AREN'T like Mendel said For detailed notes (PowerPoints) visit www.BiologyForBastards.com --- Send in a voice message: https://anchor.fm/bioforbastards/message
Doom Doom! Nostalgia. The Martian moons Crappy moons that can barely form a potato. Phobos and Deimos. Delineating between moons, planets, and all the other stuff. The likely origin of the Martian moons. Space marines Corporate space settlement and operations. Space Force. Josh reviews space marines; again. Martian weaponry. Settling mars Where to build? The cost of scratch settlement construction. Caves and lava tubes. Teleporting resources changes the game. Ancient aliens The Prometheus Problem, again. Doom humans-on-mars hypotheses: aliens developed humans on Mars vs humans originated on Mars. Species resurrection. Gene therapy. Chromosomal addition and subtraction. Martian miscellany Nano walls! Water on Mars! Telefragging! Science Fiction Film Podcast: LSG Media The X-Files Podcast: LSG Media Masters of Doom by David Kushner: iTunesAmazon Support the show!
Cancer Grand Rounds Lectures from the Norris Cotton Cancer Center Podcasts
Norris Cotton Cancer Center Grand Rounds presented on November 28, 2017 by Samuel Bakhoum, MD, PhD Senior Resident and Holman Research Fellow in Radiation Oncology Memorial Sloan Kettering Cancer Center
Chase has Chromosomal Deletion 9Q, a rare genetic condition, and a cleft lip and palate. Despite all the unknowns, his parents live each day to the fullest.
Nicole Hoppman, Ph.D. discusses ordering scenarios of the Cell-Free DNA Prenatal Screen. This test detects common chromosome abnormalities without the risk of pregnancy loss associated with invasive prenatal procedures. Chromosomal aneuploidy is the leading known genetic cause of miscarriage and congenital birth defects, including Down syndrome, trisomy 13, and trisomy 18. This fetal DNA screening test is not diagnostic. Abnormal results should be confirmed with invasive prenatal diagnostic testing (such as chorionic villi sampling or amniocentesis). Genetic consultation is recommended.
Nicole Hoppman, Ph.D. provides an overview of the Cell-Free DNA Prenatal Screen. This test detects common chromosome abnormalities without the risk of pregnancy loss associated with invasive prenatal procedures. Chromosomal aneuploidy is the leading known genetic cause of miscarriage and congenital birth defects, including Down syndrome, trisomy 13, and trisomy 18. This fetal DNA screening test is not diagnostic. Abnormal results should be confirmed with invasive prenatal diagnostic testing (such as chorionic villi sampling or amniocentesis). Genetic consultation is recommended.
Nicole Hoppman, Ph.D. discusses advantages of the Cell-Free DNA Prenatal Screen. This test detects common chromosome abnormalities without the risk of pregnancy loss associated with invasive prenatal procedures. Chromosomal aneuploidy is the leading known genetic cause of miscarriage and congenital birth defects, including Down syndrome, trisomy 13, and trisomy 18. This fetal DNA screening test is not diagnostic. Abnormal results should be confirmed with invasive prenatal diagnostic testing (such as chorionic villi sampling or amniocentesis). Genetic consultation is recommended.
Nicole Hoppman, Ph.D. discusses clinical application of Cell-Free DNA Prenatal Screen. This test detects common chromosome abnormalities without the risk of pregnancy loss associated with invasive prenatal procedures. Chromosomal aneuploidy is the leading known genetic cause of miscarriage and congenital birth defects, including Down syndrome, trisomy 13, and trisomy 18. This fetal DNA screening test is not diagnostic. Abnormal results should be confirmed with invasive prenatal diagnostic testing (such as chorionic villi sampling or amniocentesis). Genetic consultation is recommended.
Chromosomal microarray technology (CMA) facilitates the genetic diagnosis of intellectual disabilities, autism spectrum disorder, and congenital abnormalities in children. Previously, G-band karyotyping was the test performed for this purpose but it could only identify very large chromosomal abnormalities and was not very sensitive. Being a molecular rather than microscopic technique, CMA is far more sensitive for identifying genetic abnormalities and is now the test of choice. We interview David H. Ledbetter, MD, and Christa Lese Martin, PhD, from Geisinger Health System, authors of this JAMA Insights article. Articles discussed in this episode: Chromosomal Microarray Testing for Children With Unexplained Neurodevelopmental Disorders New Approaches to Molecular Diagnosis
Dr. Katherine Hyland explains the basics of the sex chromosomes and supplies some food for thought regarding the pairing of these chromosomes and the consequences of their vastly different structures. Series: "Wellbeing " [Health and Medicine] [Show ID: 31240]
Dr. Katherine Hyland explains the basics of the sex chromosomes and supplies some food for thought regarding the pairing of these chromosomes and the consequences of their vastly different structures. Series: "Wellbeing " [Health and Medicine] [Show ID: 31240]
Guest Dr. Eirini Papapetrou, an associate professor at the Icahn School of Medicine at Mt. Sinai where she discusses her work and latest paper on using stem cells to model blood diseases containing a chromosomal…
Extreme sports, extreme eating, extreme weight loss, extreme makeovers, just when you think you've heard it all, how about Extreme PCR?
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 05/06
Fri, 6 Sep 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16812/ https://edoc.ub.uni-muenchen.de/16812/1/Kuznetsova_Anastasia.pdf Kuznetsova, Anastasia ddc:570, ddc:500, Fakultät für Biologie
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 15/19
Chromosomal translocations are common in human leukemias. Detailed studies of chromosomal translocation have been useful in understanding the pathogenesis and identifying therapeutic targets in hematologic malignancies. Some translocations result in the formation of fusion genes. These fusion proteins play an important role in leukemogenesis. The t(10;11)(p12;q14) translocation is rare but recurring and results in the formation of the CALM/AF10 fusion protein. Patients with this translocation have a bad prognosis. To understand how CALM/AF10 leads to leukemia, various mouse models have been established. In a murine bone marrow retroviral transduction and transplantation model Deshpande et al. (2006) showed that mice expressing CALM/AF10 in their bone marrow cells developed an acute myeloid leukemia with a penetrance of 100% and a short latency period of 110 days. Using a transgenic mouse model, in which CALM/AF10 was under the control of Vav promoter, Peter Aplan and colleagues demonstrated that only 40% to 50% of mice developed leukemia after a long latency of 10 to 12 months. Two classical transgenic CALM/AF10 models were established in our group using the immunoglobulin heavy chain enhancer/promoter (IgH-CALM/AF10) and proximal murine LcK promoter (pLck-CALM/AF10) to drive CALM/AF10 expression. These transgenic mice did not show any leukemic phenotype even after an observation period of 15 months. Taken together these studies strongly suggest that additional collaborating factors are required for the CALM/AF10 fusion gene to induce leukemia. Meis1, a Hox cofactor, is known to collaborate with several Hox genes and Hox fusion genes such as HOXA9 and NUP98-HOXD13. In these studies, Meis1 played a critical role in accelerating the development of leukemia. It could also be shown that MEIS1 is highly expressed in CALM/AF10 positive human leukemia cells. Therefore, I sought to determine whether the homeobox gene Meis1 collaborates with CALM/AF10 in inducing leukemia. In order to achieve this goal, lethally irradiated non-transgenic mice were transplanted with IgH-CALM/AF10 transgenic bone marrow cells transduced with a Meis1 expressing retrovirus. The transplanted mice developed an acute leukemia with a penetrance of 100% and a median latency period of 187 days. The leukemia showed predominantly myeloid features such as the presence of myeloid marker positive cells. The myeloid blast cells infiltrated in multiple hematopoietic as well as non-hematopoietic organs. The leukemic cells were also positive for the B-cell marker B220. Cells that were positive for both lymphoid and myeloid markers, a characteristic feature of CALM/AF10-induced leukemia, were also detected in all the mice. The leukemic cells had clonal DJH rearrangements. Overall, these data suggest that the transformed cell might be an early progenitor cell capable of lymphoid as well as myeloid differentiation or that the leukemia was initiated by a B220+ IgH DJ rearranged cell with blocked lymphoid differentiation, which started a default myeloid differentiation program. By performing serial secondary and tertiary transplantations the leukemic nature of the disease could be confirmed. Colony forming cell assays showed that CALM/AF10 in collaboration with Meis1 failed to induce the transformation of hematopoietic progenitors in vitro. This could either be due to the lack of required growth factors and conditions necessary for the proliferation of the transformable cell or lack of additional events essential for progression towards leukemia development. In conclusion, I have demonstrated that Meis1 collaborates with CALM/AF10 in inducing acute myeloid leukemia. Additional, detailed analyses of the leukemia initiating cell in these models would help to better understand the pathogenesis of CALM/AF10-induced leukemia.
Pregnant women identified as high risk based on the prenatal screen can then undergo invasive procedures such as amniocentesis to confirm the diagnosis. Unfortunately, a large number of women with unaffected pregnancies undergo invasive procedures, putting the fetus at unnecessary risk for miscarriage.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 14/19
Morbus Fabry wird X-chromosomal vererbt und führt durch einen Defekt des lysosomalen Enzyms α-Galaktosidase A zu einer Störung im Glykosphingolipid-Katabolismus. Neutrale Glykosphingolipide, v.a. Gb3 (Globotriaosylceramid), akkumulieren in Lysosomen verschiedenster Gewebe. Mit zunehmender Ablagerung dieser Stoffe im Gefäßendothel und in den Organen kommt es zur Ausprägung der Krankheitssymptome. In der Kindheit beginnt die Erkrankung häufig mit Akroparästhesien und Angiokeratomen. Im weiteren Verlauf treten dann die lebenslimitierenden Manifestationen dieser Erkrankung auf, wie terminale Niereninsuffizienz und, durch Ischämie- und Infarktereignisse, Myokardinfarkt und zerebrale Ischämie. Im Gegensatz zur überwiegenden Mehrzahl anderer X-gebundener Erkrankungen zeigen bei Morbus Fabry nahezu alle heterozygoten Mutationsträgerinnen im Laufe der Zeit klinische Manifestationen dieser Erkrankung, teils in gleich schwerer Form wie männliche Patienten. Da bisherige Hypothesen davon ausgingen, dass eine Verschiebung der X-Inaktivierung zugunsten des mutierten GLA-Allels am Auftreten von Symptomen bei heterozygoten Fabry-Mutationsträgerinnen beteiligt sei, wurden die X-Inaktivierungsmuster von durch Mutationsanalyse gesicherten Morbus Fabry-Patientinnen mit Hilfe des Androgenrezeptor-Tests untersucht. Bei diesem Assay wird genomische DNA mit methylierungssensitiven Restriktionsenzymen inkubiert. Diese verdauen nur die unmethylierte DNA des aktiven X-Chromosoms, so dass in der anschließenden PCR-Amplifikation eines hochpolymorphen CAG-Repeats im Exon 1 des Androgenrezeptor-Gens lediglich Allele des inaktiven X-Chromosoms amplifiziert werden. Nach der automatisierten Auswertung mittels Fragmentanalyse, ermöglicht durch einen mit einem Fluoreszenzfarbstoff markierten PCR-Primer, zeigt das Verhältnis der zwei Androgenrezeptor-Allele zueinander die relative Häufigkeit eines jeden Allels auf dem aktiven oder inaktiven X-Chromosom in den Zellen des untersuchten Materials. Erstmals wurden im Rahmen der vorliegenden Arbeit die X-Inaktivierungsmuster heterozygoter Mutationsträgerinnen von Morbus Fabry im Vergleich zu einem nichtverwandten Kontrollkollektiv untersucht. 13 (46%) der 28 Fabry-Mutationsträgerinnen zeigten eine random X-Inaktivierung, 10 (36%) eine moderate Verschiebung der X-Inaktivierung und 5 (18%) eine ausgeprägte Verschiebung der X-Inaktivierung zugunsten eines Allels. Es zeigte sich kein statistisch signifikanter Unterschied zu den Inaktivierungsmustern gleichaltriger Kontrollen (p = 0,669). Segregationsanalysen konnten anhand der Familien von sechs Frauen mit ausgeprägter oder moderater Verschiebung der X-Inaktivierung durchgeführt werden. Hier zeigte sich bei vier dieser Frauen eine Verschiebung der X-Inaktivierung zugunsten des Wildtyp GLA-Allels, während bei zwei weiteren eine Verschiebung zugunsten des mutierten Allels in Leukozyten erkennbar war. Bei jeder der Fabry-Patientinnen war sowohl der klinische Schweregrad der Erkrankung mittels MSSI (Mainz Severity Score Index), einem detaillierten Scoring-System für Morbus Fabry, als auch die Enzymaktivität der α-Galaktosidase A bestimmt worden. Eine Korrelation zwischen dem Ausmaß der X-Inaktivierung in Leukozyten heterozygoter Fabry-Mutationsträgerinnen und deren klinischen oder biochemischen Krankheitsparametern konnte jedoch nicht nachgewiesen werden. In dieser Studie konnte gezeigt werden, dass heterozygote Fabry-Patientinnen random X-Inaktivierungsmuster ähnlich denen gesunder Frauen aufweisen. Anhand unserer Daten konnte nicht belegt werden, dass das Auftreten und der Schweregrad der Erkrankung bei der Mehrzahl der heterozygoten Fabry-Patientinnen auf eine Verschiebung der X-Inaktivierung zugunsten des mutierten Allels als Pathomechanismus zurückzuführen ist. X-Inaktivierungsstudien können jedoch dazu beitragen, jene Frauen frühzeitig herauszufiltern, welche aufgrund einer bei ihnen möglicherweise rascher progredient verlaufenden Erkrankung von einer sehr teuren Enzymersatztherapie am meisten profitieren könnten.
Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL) system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs) lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Wed, 18 May 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13089/ https://edoc.ub.uni-muenchen.de/13089/1/Kemkener_Claus.pdf Kemkemer, Claus Stefan Oliver ddc:570, ddc:500, Fakultät für
Video PodcastAired date: 2/9/2011 3:00:00 PM Eastern Time
Audio PodcastAired date: 2/9/2011 3:00:00 PM Eastern Time
What are Y-Chromosomal Adam and Mitochondrial Eve? Is there really scientific evidence that everyone alive descended from one woman? Is there really scientific that every man alive today can trace his ancestry back to one man?
The histone methyltransferase SU(VAR)3-9 plays an important role in the formation of heterochromatin within the eukaryotic nucleus. Several studies have shown that the formation of condensed chromatin is highly regulated during development, suggesting that SU(VAR)3-9's activity is regulated as well. However, no mechanism by which this may be achieved has been reported so far. As we and others had shown previously that the N-terminus of SU(VAR)3-9 plays an important role for its activity, we purified interaction partners from Drosophila embryo nuclear extract using as bait a GST fusion protein containing the SU(VAR)3-9 N-terminus. Among several other proteins known to bind Su(VAR)3-9 we isolated the chromosomal kinase JIL-1 as a strong interactor. We show that SU(VAR)3-9 is a substrate for JIL-1 in vitro as well as in vivo and map the site of phosphorylation. These findings may provide a molecular explanation for the observed genetic interaction between SU(VAR)3-9 and JIL-1.
Keith Caldecott, Genome Damage and Stability Centre, University of Sussex, Brighton, East Susses, UK speaks on "Chromosomal single-strand break repair and human genetic disease". This seminar has been recorded by ICGEB Trieste
Dr. Michael Cleary discusses this work on the role of chromosomal aberrations in causing cancer and its implications for cancer treatment. (September 18, 2008)
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Fri, 16 Jan 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/12589/ https://edoc.ub.uni-muenchen.de/12589/1/Klein_Ulf.pdf Klein, Ulf ddc:570, ddc:500, Fakultät für Biologie
Dosage compensation in male Drosophila relies on the X chromosome-specific recruitment of a chromatin-modifying machinery, the dosage compensation complex (DCC). The principles that assure selective targeting of the DCC are unknown. According to a prevalent model, X chromosome targeting is initiated by recruitment of the DCC core components, MSL1 and MSL2, to a limited number of so-called ``high-affinity sites'' ( HAS). Only very few such sites are known at the DNA sequence level, which has precluded the definition of DCC targeting principles. Combining RNA interference against DCC subunits, limited crosslinking, and chromatin immunoprecipitation coupled to probing high-resolution DNA microarrays, we identified a set of 131 HAS for MSL1 and MSL2 and confirmed their properties by various means. The HAS sites are distributed all over the X chromosome and are functionally important, since the extent of dosage compensation of a given gene and its proximity to a HAS are positively correlated. The sites are mainly located on noncoding parts of genes and predominantly map to regions that are devoid of nucleosomes. In contrast, the bulk of DCC binding is in coding regions and is marked by histone H3K36 methylation. Within the HAS, repetitive DNA sequences mainly based on GA and CA dinucleotides are enriched. Interestingly, DCC subcomplexes bind a small number of autosomal locations with similar features.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Mon, 31 Mar 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/8391/ https://edoc.ub.uni-muenchen.de/8391/1/Epanchintsev_Alexey.pdf Epanchintsev, Alexey ddc:
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Nasonia vitripennis is a small parasitic hymenopteran with a 50-year history of genetic work including linkage mapping with mutant and molecular markers. For the first time we are now able to anchor linkage groups to specific chromosomes. Two linkage maps based on a hybrid cross (N. vitripennis x N. longicornis) were constructed using STS, RAPID and microsatellite markers, where 17 of the linked STS markers were developed from single microdissected banded chromosomes. Based on these microdissections we anchored all linkage groups to the five chromosomes of N. vitripennis. We also verified the chromosomal specificity of the microdissection through in situ hybridization and linkage analyses. This information and technique will allow us in the future to locate genes or QTL detected in different mapping populations efficiently and fast on homologous chromosomes or even chromosomal regions. To test this approach we asked whether QTL responsible for the wing size in two different hybrid crosses (N. vitripennis x N. longicornis and N. vitripennis x N. giraulti) map to the same location. One QTL with a major effect was found to map to the centromere region of chromosome 3 in both crosses. This could indicate that indeed the same gene/s is involved in the reduction of wing in N. vitripennis and N. longicornis. Copyright (C) 2003 S. Karger AG, Basel.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
The aim of this work was to describe the importance of the estimation of the quality of cattle embryos in embryo transfer as well as to discuss the causes of the appearance of the variable embryo qualities after superovulation and the different possibilities to assess the embryo quality. After superovulation there are always variable embryo quality observed. The reasons for this are versatile. An important, the result of a superovulation treatment influencing factor, is the donor cow. Both the individual disposition, the age and as well healthy status and the stressexposition of the animals are playing an important role. The ovary reactions are rather essentially influenced by the existence of a dominant follicle at the moment of introduction of a superovulation treatment. By removal of dominant follicle the results can significant be improved. Another important factor is the sort of a gonadotrophin used for superovulation. The reaction to a superovulation treatment is not just depending on the selection of the gonadotroph hormone, but also on the composition of the preparations, the doses und the way of application. Because the morphological evaluation of embryo quality is subjected to subjective influences, it should attach importance to the training of the evaluating persons, to receive comparable results. The importance of assessment of embryo quality to select embryos is considerable. The results of embryo transfer, the pregnancy rates, are essentially depending on the quality of the transferred embryos. The survival of embryos after kryopreservation is also influenced by the embryo quality. Embryo quality can be evaluated by different approaches: if the selected embryo has to be transferred, the technique to estimate embryo quality must not be invasive. In the practice of the embryo transfer embryo quality is estimated before transfer by gross embryo morphology. However, this method is a rather subjective possibility for assessment of the embryo quality. More accurate date can be obtained by the use of invasive techniques. Metabolic tests to evaluate embryo viability include measurement of nutrient uptake, energy metabolism and oxygen uptake. Enzyme leakage and hormone or growth factor production can also give more details on the quality of embryos. Techniques which might partially are able to affect the embryo are the determination of the freezing resistance and vital staining. With vital staining, membrane integrity, which is critical for embryo survival, can be assessed by means of fluorescent probes. The most common staining methods for evaluating embryo quality are DAPI and FDA. These two fluorescent probes do not alter the embryo, so that you can still transfer the embryo after these examinations. Invasive assessment of the embryo quality mostly involves a kind of fixation or staining of the embryo and so they are not suitable for the practical use of the embryo transfer. Cytogenetic analysis of embryos is an important issue for caryotyping. Chromosomal deviations are known to cause early embryonic mortality in cattle. Determination of the total cell number and the allocation of these cells to the inner cell mass (ICM) and trophectoderm (TE) after differential staining of these cells give more details on the quality of an embryo.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 01/19
Die X-chromosomal gebundene Adrenoleukodystrophie stellt eine vererbte Störung der peroxisomalen ß-Oxidation von Fettsäuren dar, die zu einer Akkumulation von überlangkettigen Fettsäuren in allen Körperflüssigkeiten führt. X-ALD wird durch Mutationen im ALD-Gen verursacht, welches ein peroxisomales Membranprotein aus der Superfamilie der ABCTransporter (ATP-binding cassette) kodiert. Die Erkrankung führt zu einer fortschreitenden Demyelinisierung des ZNS, einer peripheren Neuropathie sowie adrenokortikaler Insuffizienz. Es findet sich jedoch eine sehr hohe Variabilität phänotypischer Verlaufsformen. Aus bislang unklaren Gründen zeigt ein Großteil der heterozygoten Überträgerinnen - im Gegensatz zu der überwiegenden Mehrzahl anderer X-chromosomal vererbter Erkrankungen - sowohl die biochemischen als auch die klinischen Merkmale einer X-ALD in abgemilderter Form. Zur Erklärung dieses Phänomens sollte die Untersuchung der X-Inaktivierung heterozygoter Überträgerinnen beitragen, da in der Vergangenheit postuliert wurde, daß eine zugunsten des mutierten ALD-Allels verschobene X-Inaktivierung (mit-)verantwortlich sei für das Auftreten erhöhter Konzentrationen überlangkettiger Fettsäuren und neurologischer Symptome bei ALDÜberträgerinnen. Zur Untersuchung der X-Inaktivierung wurde der hochinformative Androgenrezeptor-Test etabliert und in einigen Punkten modifiziert und verbessert. Das Testprinzip beruht auf der PCRAmplifikation eines hochpolymorphen CAG-Repeats im Exon 1 des Androgenrezeptor-Gens nach einer Inkubation von genomischer DNA mit methylierungssensitiven Restriktionsenzymen. Die Verwendung eines fluoreszenz-markierten Primers in der PCR ermöglichte eine präzise automatisierte Auswertung mittels Fragmentanalyse. Neben einer Bestimmung der überlangkettigen Fettsäuren im Plasma wurde der Heterozygotenstatus der ALD-Überträgerinnen durch eine Mutationsanalyse des ALD-Gens eindeutig belegt. Dabei konnten in allen 15 untersuchten Familien Mutationen im ALD-Gen identifiziert werden. Bei 8 Familien fanden sich neue, bislang unveröffentlichte Mutationen. Das Mutationsspektrum umfaßte 10 Missense- (67 %), zwei Nonsense- (13 %), zwei Splice-Site- Mutationen (13 %) und eine Frameshift-Mutation (6 %). Die X-Inaktivierungsmuster in Leukozyten heterozygoter ALD-Überträgerinnen wurden erstmals im Vergleich zu einem verwandten und einem nicht-verwandten Kontrollkollektiv untersucht. Bei 7 von 22 Überträgerinnen (32 %) zeigte sich eine ausgeprägte Verschiebung der X-Inaktivierung (Skewing) zugunsten eines Allels (> 80:100). Im Gegensatz dazu war ein ausgeprägtes Skewing weder bei den Nicht-Überträgerinnen aus ALD-Familien noch bei den Kontrollen zu beobachten. In diesen Gruppen fanden sich nur random X-Inaktivierung und mildes Skewing zu annähernd gleichen Teilen. Bei beiden Gruppen glich die Verteilung der XInaktivierungsmuster einer Gauss’schen Normalverteilungskurve. Die Unterschiede zwischen ALD-Überträgerinnen und unverwandtem Kontrollkollektiv erwiesen sich als statistisch hochsignifikant. Eine Korrelation zwischen dem Grad der X-Inaktivierung in Leukozyten heterozygoter ALDÜberträgerinnen und deren biochemischen Parametern (Konzentration überlangkettiger Fettsäuren im Plasma) war nicht nachweisbar. Unsere Daten belegen, daß das häufige Auftreten einer Verschiebung der X-Inaktivierung zugunsten eines Allels bei ALD-Überträgerinnen mit dem mutierten ALD-Allel in Zusammenhang steht und wahrscheinlich durch Selektionsmechanismen verursacht wird. Diese Selektionsmechanismen wirken nach dem primären X-Inaktivierungsprozeß. Andere sekundäre Einflußvariablen wie Alter oder genetische Faktoren des X-Inaktivierungsprozesses selbst wurden mit hoher Wahrscheinlichkeit ausgeschlossen. Anhand von Transkriptanalysen in kultivierten Fibroblasten konnte darüberhinaus gezeigt werden, daß einerseits eine Selektion zugunsten des Wildtyp-Allels, andererseits jedoch auch eine Selektion zugunsten des mutierten Allels vorkommt. Der bislang in der Literatur postulierte Selektionsvorteil des mutierten ALD-Allels wird somit in Frage gestellt.
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Eleven uveal melanomas were analyzed using comparative genomic hybridization (CGH). The most abundant genetic changes were loss of chromosome 3, overrepresentation of 6p, loss of 6q, and multiplication of 8q. The smallest overrepresented regions on 6p and 8q were 6pterp21 and 8q24qter, respectively. Several additional gains and losses of chromosome segments were repeatedly observed, the most frequent one being loss of 9p (three cases). Monosomy 3 appeared to be a marker for ciliary body involvement. CGH data were compared with the results of chromosome banding. Some alterations, e.g., gains of 6p and losses of 6q, were observed with higher frequencies after CGH, while others, e.g., 9p deletions, were detected only by CGH. The data suggest some similarities of cytogenetic alterations between cutaneous and uveal melanoma. In particular, the 9p deletions are of interest due to recent reports about the location of a putative tumor-suppressor gene for cutaneous malignant melanoma in this region.
Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue.
We have isolated a full-length mouse cDNA encoding a lysine-rich protein of 1,131 amino acids with a calculated molecular mass of 126 kDa. The protein binds in a sequence-unspecific manner to DNA, is localized exclusively in the nucleus, and contains a putative ATP binding site and a stretch of 80 amino acids with homology to the carboxy terminus of prokaryotic DNA ligases. On the basis of the following facts, we conclude that the isolated cDNA encodes the 140-kDa subunit of mouse replication factor C (mRFC140). (i) The sequence around the ATP binding site shows significant homology to three small subunits of human replication factor C. (ii) Polyclonal antibodies raised against the protein encoded by this cDNA cross-react with the 140-kDa subunit of purified human replication factor C (hRFC140) and recognize in mouse cell extracts an authentic protein with an apparent molecular mass of 130 kDa. (iii) Sequence comparison with a human cDNA isolated by using tryptic peptide sequence information from purified hRFC140 revealed 83% identity of the encoded proteins. The mRFC140 gene is ubiquitously expressed, and two mRNAs approximately 5.0 and 4.5 kb long have been detected. The gene was mapped by in situ hybridization to mouse chromosome 5, and its human homolog was mapped to chromosome 4 (p13-p14).
The frequency of DNA double-strand breaks (dsb) was determined in yeast cells exposed to γ-rays under anoxic conditions. Genomic DNA of treated cells was separated by pulsed field gel electrophoresis, and two different approaches for the evaluation of the gels were employed: (1) The DNA mass distribution profile obtained by electrophoresis was compared to computed profiles, and the number of DSB per unit length was then derived in terms of a fitting procedure; (2) hybridization of selected chromosomes was performed, and a comparison of the hybridization signals in treated and untreated samples was then used to derive the frequency of dsb.
Colored chromosome staining patterns, termed chromosomal ‘bar codes’ (CBCs), were obtained on human chromosomes by fluorescence in situ hybridization (FISH) with pools of Alu-PCR products from YAC dones containing human DNA inserts ranging from 100 kbp to 1 Mbp. In contrast to conventional G- or R-bands, the chromosomal position, extent, Individual color and relative signal intensity of each ‘bar’ could be modified depending on probe selection and labeling procedures. Alu-PCR amplification products were generated from 31 YAC clones which mapped to 37 different chromosome bands. For multiple color FISH, Alu-PCR amplification products from various clones were either biotinylated or labeled with digoxigenin. Probes from up to twenty YAC clones were used simultaneously to produce CBCs on selected human chromosomes. Evaluation using a cooled CCD camera and digital image analysis confirmed the high reproducibility of the bars from one metaphase spread to another. Combinatorial FISH with mixtures of whole chromosome paint probes was applied to paint seven chromosomes simultaneously in different colors along with a set of YAC clones which map to these chromosomes. We discuss the potential to construct analytical chromosomal bar codes adapted to particular needs of cytogenetic investigations and automated image analysis.
A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1–q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5′ and 3′ regions of the genes, are as follows: cen/3′-CGM7-5′/3′-CGM2-5′/5′-CEA-3′/5′-NCA-3′/5′- CGM1-3′/3′-BGP-5′/3′-CGM9-5′/3′-CGM6-5′/5′-CGM8-3′/PSGcluster/qter.
The existence of an apomorphic reciprocal chromosomal translocation in the gorilla lineage has been asserted or denied by various cytogeneticists. We employed a new molecular cytogenetic strategy (chromosomal in situ suppression hybridization) combined with high-resolution banding, replication sequence analysis, and fluorochrome staining to demonstrate that a reciprocal translocation between ancestral chromosomes homologous to human chromosome 5 and 17 has indeed occurred.
Chromosomal in situ suppression (CISS) hybridization was performed with library DNA from sorted human chromosomes 8, 9, 15, 17, 21, and 22 on immunologically stained bone marrow cells of four patients with a hematologic neoplasm, including two patients with myelodysplastic syndrome and trisomy 8, one patient with promyelocytic leukemia bearing the translocation t(15;17)(q22;q11-12), and one patient with chronic myeloid leukemia and the translocation t(9;22)(q34;q11). In all patients, the results of conventional karyotype analysis could be confirmed by one- or two-color CISS hybridization using the appropriate chromosome-specific libraries. Our results show that CISS hybridization can detect both numerical and structural chromosome changes in immunologically classified cells with high specificity and reliability. The fact that chromosome spreads of very poor quality can now be included in such analyses is a decisive advantage of this approach. In addition, the suitability of this approach for interphase cytogenetics is discussed.
In situ suppression hybridization with recombinant bacteriophage DNA libraries for chromosomes 8 and 21 was performed in two cases of acute nonlymphocytic leukemia, type FAB M2. In both cases, cytogenetic analysis by conventional G-banding revealed t(8;21)(q22;q22). In situ suppression hybridization was able to prove the reciprocal nature of the translocation in both cases by identifying the terminal end of chromosome 21 translocated to the derivative chromosome 8q−.
Tue, 1 Jan 1991 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9347/1/9347.pdf Cremer, Thomas; Greulich, K. O.; Lichter, Peter; Ponelies, N.; Endlich, N.; Weith, A.; Eckelt, A.; Lengauer, Christoph
A new strategy for analyzing chromosomal evolution in primates is presented using chromosomal in situ suppression (CISS) hybridization. Biotin-labeled DNA libraries from flow-sorted human chromosomes are hybridized to chromosome preparations of catarrhines, platyrrhines, and prosimians. By this approach rearrangements of chromosomes that occurred during hominoid evolution are visualized directly at the level of DNA sequences, even in primate species with pronounced chromosomal shuffles.
Chromosomal in situ suppression (CISS)-hybridization of biotinylated phage DNA-library inserts from sorted human chromosomes was used to decorate chromosomes 1 and 7 specifically from pter to qter and to detect structural aberrations of these chromosomes in irradiated human peripheral lymphocytes. In addition, probe pUC1.77 was used to mark the Iq12 subregion in normal and aberrant chromosomes 1. Low LET radiation (60Co--rays; 1.17 and 1.33 MeV) of lymphocyte cultures was performed with various doses (D = 0, 2, 4, 8 Gy) 5 h after stimulation with phytohaemagglutinin. Irradiated cells were cultivated for an additional 67 h before Colcemid arrested metaphase spreads were obtained. Aberrations of the specifically stained chromosomes, such as deletions, dicentrics, and rings, were readily scored after in situ hybridization with either the 1q12 specific probe or DNA-library inserts. By the latter approach, translocations of the specifically stained chromosomes could also be reliably assessed. A linear increase of the percentage of specifically stained aberrant chromosomes was observed when plotted as a function of the square of the dose D. A particular advantage of this new approach is provided by the possibility to delineate numerical and structural chromosome aberrations directly in interphase nuclei. These results indicate that cytogenetic monitoring of ionizing radiation may be considerably facilitated by CISS-hybridization.
DNA libraries from sorted human gonosomes were used selectively to stain the X and Y chromosomes in normal and aberrant cultured human cells by chromosomal in situ suppression (CISS-) hybridization. The entire X chromosome was stained in metaphase spreads. Interphase chromosome domains of both the active and inactive X were clearly delineated. CISS-hybridization of the Y chromosome resulted in the specific decoration of the euchromatic part (Ypter-q11), whereas the heterochromatic part (Yq12) remained unlabeled. The stained part of the Y chromosome formed a compact domain in interphase nuclei. This approach was applied to amniotic fluid cells containing a ring chromosome of unknown origin (47,XY; +r). The ring chromosome was not stained by library probes from the gonosomes, thereby suggesting its autosomal origin. The sensitivity of CISS-hybridization was demonstrated by the detection of small translocations and fragments in human lymphocyte metaphase spreads after irradiation with 60Co-gamma-rays. Lymphocyte cultures from two XX-males were investigated by CISS-hybridization with Y-library probes. In both cases, metaphase spreads demonstrated a translocation of Yp-material to the short arm of an X chromosome. The translocated Y-material could also be demonstrated directly in interphase nuclei. CISS-hybridization of autosomes 7 and 13 was used for prenatal diagnosis in a case with a known balanced translocation t(7;13) in the father. The same translocation was observed in amniotic fluid cells from the fetus. Specific staining of the chromosomes involved in such translocations will be particularly important, in the future, in cases that cannot be solved reliably by conventional chromosome banding alone.
Repeated DNAs from the constitutive heterochromatin of human chromosomes 1 and 18 were used as probes in nonradioactive in situ hybridization experiments to define specific numerical and structural chromosome aberrations in three human glioma cell lines and one neuroblastoma cell line. The number of spots detected in interphase nuclei of these tumor cell lines and in normal diploid nuclei correlated well with metaphase counts of chromosomes specifically labeled by in situ hybridization. Rapid and reliable assessments of aneuploid chromosome numbers in tumor lines in double hybridization experiments were achieved, and rare cells with bizarre phenotype and chromosome constitution could be evaluated in a given tumor cell population. Even with suboptimal or rare chromosome spreads specific chromosome aberrations were delineated. As more extensive probe sets become available this approach will become increasingly powerful for uncovering various genetic alterations and their progression in tumor cells.
Fri, 1 Jan 1988 12:00:00 +0100 https://epub.ub.uni-muenchen.de/5375/1/Zimmermann_Wolfgang_5375.pdf Thompson, John A.; Kleist, Sabine von; Shively, John E.; Fiebig, Heinz-Herbert; Schempp, Werner; Rudert, Fritz; Ortlieb, Barbara; Weber, Bernhard; Zimmermann, Wolfgang
Plasmid clones containing up to 94 kilobases of single-copy DNA from band q22.3 of chromosome 21 and a complete pool of insert DNA from a chromosome 21 recombinant library have been used to rapidly detect numerical and structural aberrations of chromosome 21 by in situ hybridization in both metaphase and interphase cells. A trisomic karyotype, diagnostic of Down syndrome, is readily detected in nonmitotic cells because the majority of their nuclei exhibit three discrete foci of hybridization, in contrast to normal diploid cells, which show two foci. Chromosomal translocations involving chromosome 21 sequences were also detected with these probes, and the intranuclear location of 21q22.3 DNA sequences in "normal" human brain neurons was established with the plasmid DNA probe set. These results suggest that chromosome 21-specific probes may have utility in clinical diagnostics, especially by facilitating the direct analysis of interphase cells.
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