When Wellcome Sanger Institute geneticist Eugene Gardner set out to look for a specific type of genetic mutation in a massive database of human DNA, he figured itd be a long shot. Transposonsalso known as jumping genes because they can move around the genomecreate a new mutation in one of every 15 to 40 human births, but thats across the entire 3 billion base pairs of nuclear DNA that each cell carries. The sequencing data that Gardner was working with covered less than two percent of that, with only the protein-coding regions, or exons, included. Doing a quick calculation, he determined that, in the best-case scenario, he could expect to find up to 10 transposon-generated variants linked to a developmental disease. And we really might get zero, he says. This whole thing might be for naught.
But Gardner had recently developed the perfect tool to find the sort of de novo mobile element insertions that come about as a result of transposon movements and are often overlooked in genetic screens and analyses. As a graduate student in Scott Devines lab at the University of Maryland, Baltimores Institute for Genome Sciences, he had spent many hours making the software for the mobile element locator tool he dubbed MELT. The program was easy to use, so when Gardner moved across the Atlantic for a postdoc in Matthew Hurless lab at Sanger near Cambridge and gained access to a database of exomes from 13,000 patients with developmental disorders, he figured running the tool was worth a try.
There is tremendous value for these families that get a diagnosis.
Dan Koboldt, Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Childrens Hospital
Of those 13,000, Gardner focused on 9,738 people in the Deciphering Developmental Disorders (DDD) study whose parents exomes had also been sequenced, making it easier to single out variants present in the child but not in mom and dad. And as it turned out, he did get some hits. MELT picked up 40 potentially transposon-generated variants, which Gardner sat down at his computer to review using the raw sequencing data. Nine appeared to be true de novo mobile element insertions. I remember being in my desk doing the visualization of all the putative de novo variants after I got the first results off the pipeline, he recalls. I remember being excited: I think I might have found a diagnostic de novo!
Discussing the literature on the genes affected by such insertions with clinicians and other colleagues, Gardner narrowed the list down to four insertions found in genes that may be causing or contributing to four different patients disorders. He sent these results off to the physicians who had referred each of the patients to the database, and all the doctors confirmed that the results made sense to them given what had been published on those genes and what they knew about other cases involving patients with mutations in the same sequences. In one case, the physician had already linked the patients disorder to the gene Gardner had identified; in the other three cases, the patients were still undiagnosed.
There is tremendous value for these families that get a diagnosis, says human geneticist Dan Koboldt, who has collaborated with Hurles in the past and has used MELT in his studies of rare disease at the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Childrens Hospital in Columbus, Ohio, but who was not involved in Gardners recent study. A genetic answer not only can help physicians connect patients to appropriate medical and counseling resources; it puts an end to the diagnostic odyssey that families affected by rare disease often endure.
Whats more, the finding of four potentially causative hits out of the nearly 10,000 cases provides first estimate of how commonly such mobile element insertions underlie developmental disorders. Whats interesting about this study is that its taking a very broad approach, says Ian Adams, a developmental biologist at the University of Edinburghs MRC Human Genetics Unit who was not involved in the research. Rather than look for transposon activity in a specific disorder, its casting a much broader net in trying to find what type of diseases this class of mutations could be contributing to.
This approach is important, agrees Adamss MRC Human Genetics Unit colleague Jose Garcia-Perez, a transposable elements expert who was also not involved in the new research. In the last few years, two studies have used a tool developed around the same time as MELT to search for de novo mobile elements in people with autism spectrum disorder, but neither identified any that were likely to be responsible for the patients symptoms. [Gardners] study shows that, no matter whats [been found] recently, its something that should be explored in further detail in the future, says Garcia-Perez. [The study] actually shows a real connection between . . . transposition with that particular [type of] disorder. Koboldt adds: The reason this is an important study is that it establishes [that these] variants do occur and [that] they can be pathogenic.
Gardner says he hopes that his methods can be used to explore other diseases, from both a research and a clinical perspective. Adams says MELT does appear to be widely applicable to other datasets. Such a tool could be a boon to research on transposons, given that their movements are often missed by normal screening tools, Adams adds. I think [MELT is] something that could be readily built into existing pipelines.
Jef Akst is managing editor ofThe Scientist. Email her atjakst@the-scientist.com.
View original post here:
Transposons Identified as Likely Cause of Undiagnosed Diseases - The Scientist
- 1st draft of a human 'pangenome' published, adding millions of ... - May 17th, 2023
- A Brief Guide to Genomics - National Human Genome Research Institute - May 17th, 2023
- Human genetics - Immunogenetics | Britannica - April 23rd, 2023
- A Troublesome Inheritance - Wikipedia - April 23rd, 2023
- Human - Simple English Wikipedia, the free encyclopedia - January 29th, 2023
- Human Genetics and Genomics Training Program - Hopkins Medicine - January 4th, 2023
- Genetics vs. Genomics Fact Sheet - Genome.gov - December 18th, 2022
- Human Genetics and Molecular Biology, PhD - Johns Hopkins University - December 18th, 2022
- Race (human categorization) - Wikipedia - December 2nd, 2022
- Human Y-chromosome DNA haplogroup - Wikipedia - November 24th, 2022
- Abstracts | International Congress of Human Genetics 2023 - November 24th, 2022
- Human genetic variation - Wikipedia - November 6th, 2022
- Genetics | The Smithsonian Institution's Human Origins Program - October 29th, 2022
- Fluent BioSciences showcasing breakthrough solutions to enable unprecedented scale, cost-efficiency and access for single-cell RNA sequencing at the... - October 29th, 2022
- Researchers seek to unravel the mystery of susceptibility to drug addiction - Newswise - October 4th, 2022
- NIH initiative to systematically investigate and establish function of every human gene - National Institutes of Health (.gov) - October 4th, 2022
- ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma | Communications Biology - Nature.com - October 4th, 2022
- Does obesity have more to do with the brain than we initially thought? - Medical News Today - October 4th, 2022
- Who will get the call from Stockholm? It's time for STAT's 2022 Nobel Prize predictions - STAT - October 4th, 2022
- Solving medical mysteries: Physicians and researchers collaborate to study the most challenging cases - AAMC - October 4th, 2022
- Mystery gene matures the skeleton of the cell - EurekAlert - October 4th, 2022
- What Is The Most Important factor Driving The Global Human Genetics Market? - PharmiWeb.com - September 25th, 2022
- How Africa's genetic diversity can be harnessed to close the continent's 'drug and treatment gap' - Genetic Literacy Project - September 25th, 2022
- Ability to move to the pulse of music has genetic link - DTNEXT - September 25th, 2022
- Is the Spike Protein Changing Our Gene Expression? - The Epoch Times - September 25th, 2022
- How prehistoric DNA is helping to unlock the secrets of human evolution - EL PAS USA - September 25th, 2022
- Personalised medicine and the advantages of big data and AI-based diagnostics - Medical Device Network - September 25th, 2022
- Viewpoint: In the post Roe v Wade world, what changes should a biology textbook writer make to address the medical repercussions of Dobbs? - Genetic... - September 25th, 2022
- Bears' ability to regulate insulin narrowed down to eight proteins WSU Insider - WSU News - September 25th, 2022
- Sex, Selection and Biodiversity - Syracuse.edu - Syracuse University - September 25th, 2022
- Was the Russian Flu the first coronavirus pandemic? Find out at next Science Caf - University of Nebraska at Kearney - September 25th, 2022
- University of Chicago South Side Science Fest created to show off the fun, myriad pathways into field. - Chicago Tribune - September 25th, 2022
- The genetics of human personality - PubMed - August 14th, 2022
- Genetics - The Harvey Institute for Human Genetics - GBMC HealthCare in ... - August 14th, 2022
- Degrees of the Future 2022: Genetics - Gizmodo - August 14th, 2022
- U of U Health-Led Research Awarded $28 Million to Explore HIV's Inner Workings and Vulnerabilities - University of Utah Health Care - August 14th, 2022
- Revisiting Companies That Had Their IPO in 2018 - Investment U - August 14th, 2022
- Monkeypox Myth Busting: Here's What You Need to Know - The Mighty - August 14th, 2022
- Relay Therapeutics Reports Second Quarter 2022 Financial Results and Corporate Highlights - Yahoo Finance - August 5th, 2022
- Baylor receives NCI grant to study liver cancer risk and prevention - Baylor College of Medicine News - August 5th, 2022
- Whole Exome Sequencing Market reach a valuation of US$ 4,256.30 Mn, at a CAGR of 19.24% in the Forecast 2030 - BioSpace - August 5th, 2022
- Mendels Genetic Revolution and the Legacy of Scientific Racism - NewsClick - August 5th, 2022
- AMGEN TO ACQUIRE CHEMOCENTRYX FOR $4 BILLION IN CASH - BioSpace - August 5th, 2022
- Cotton Buds Market Value Is Estimated to Reach USD 747.16 BN By 2028, With 3.2% CAGR Credence Research - Digital Journal - August 5th, 2022
- Verve Therapeutics Shares Up 84%; ARKG Offers Exposure - ETFdb.com - July 27th, 2022
- Double up on the guac? Those avocados are good for your heart health - American Heart Association - July 27th, 2022
- Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome | European Journal of Human Genetics - Nature.com - July 27th, 2022
- Scientists Unravel the Mystery of Junk Genes That Are Key to Brain Development - SciTechDaily - July 27th, 2022
- COVID-19 Can Make the Brain Age by 2 Decades; Here's 1 Way to Reverse Aging - The Epoch Times - July 27th, 2022
- Mice Model Market Forecast to 2028 - COVID-19 Impact and Global Analysis By Type, Service, Technology, Indication, End User, Application, and Mode -... - July 27th, 2022
- Master's Degree in Human Genetics | Human Genetics | Michigan Medicine ... - July 11th, 2022
- Here's how the $100 Human Genome will Change Medicine - BioSpace - July 11th, 2022
- Genomic medicine: the role of the nursing workforce - Nursing Times - July 11th, 2022
- AbbVie Half Breaks Up with Alector on Alzheimer's - BioSpace - July 11th, 2022
- The human identification market size is projected to reach - GlobeNewswire - July 11th, 2022
- Global wheat production can be doubled to feed millions and save land, say scientists - Sky News - July 11th, 2022
- Huntsville native among TIMEs 100 most influential people - WHNT News 19 - July 3rd, 2022
- New hope for IVF patients as global study published in Human Reproduction shows AI can effectively assess genetic integrity of embryos - Yahoo Finance - July 3rd, 2022
- A Week At The Most Secretive Conference On Aging - Forbes - July 3rd, 2022
- Human genetics shape the gut microbiome - PMC - June 13th, 2022
- expert reaction to a conference abstract on retinal screening predicting risk of myocardial infarction - Science Media Centre - June 13th, 2022
- New Comprehensive Map Ties Every Human Gene to Its Function - SciTechDaily - June 13th, 2022
- Buffalo shooters manifesto quoted a university researcher. Thats raising questions about racism in academia - Yahoo News - June 13th, 2022
- Thalidomide could be used as a therapeutic for AVMs - Cosmos - June 13th, 2022
- How Electric Fish Were Able to Evolve Electric Organs - UT News - University of Texas - June 4th, 2022
- Survival of the Best: The Past, Present and Future of Plants - CSRwire.com - June 4th, 2022
- AMGEN ANNOUNCES WEBCAST OF 2022 JEFFERIES HEALTHCARE CONFERENCE | News | wfmz.com - 69News WFMZ-TV - June 4th, 2022
- Experts Discover New Disease Caused by Faulty Genes Affecting the Kidney and Liver: Newcastle University Study - Nature World News - June 4th, 2022
- At-Home Colorectal Cancer Testing and Follow-Up Vary by Ethnicity - Medscape - June 4th, 2022
- Who is your real parent? Our Father on Netflix depicts the dark side of 'secret serial sperm donation'. My birth has a similar origin but with a more... - June 4th, 2022
- Autism and the complete human genome: Q&A with Evan Eichler | Spectrum - Spectrum - May 15th, 2022
- Increased Mutations in Children Can Be Traced Back to Mistakes in Father's Sperm - Neuroscience News - May 15th, 2022
- Not All Is Rosy For The Pink Pigeon - Eurasia Review - May 15th, 2022
- Why haven't we cloned a human yet? - Livescience.com - May 15th, 2022
- Study probes the relationship between genetics, proteins, and disease risk - The Hub at Johns Hopkins - May 15th, 2022
- Singular Genomics Announces Formation of Scientific Advisory Board - BioSpace - May 15th, 2022
- COVID Resistance Might Be Tied To Genetics: Experts - Medical Daily - May 15th, 2022
- Letter: Why no to Roe and abortion - INFORUM - May 15th, 2022
- Gut Microbiome Composition Predictive of Patient Response to Statins - Business Wire - May 15th, 2022
- Finding A Place In Science - Texas A&M Today - Texas A&M University Today - May 15th, 2022