April 21, 2017 by Sam Sholtis Penn State researchers identified 832 genes that have low coverage across multiple whole-exome sequencing platforms. These genes are associated with leukemia, psoriasis, heart failure and other diseases, and may be missed by researchers using whole-exome sequencing to study these diseases. Credit: Penn State University, Carley LaVelle
Whole-exome DNA sequencinga technology that saves time and money by sequencing only protein-coding regions and not the entire genomemay routinely miss detecting some genetic variations associated with disease, according to Penn State researchers who have developed new ways to identify such omissions.
Whole-exome sequencing has been used in many studies to identify genes associated with disease, and by clinical labs to diagnose patients with genetic disorders. However, the new research shows that these studies may routinely miss mutations in a subset of disease-causing genesassociated with leukemia, psoriasis, heart failure and othersthat occur in regions of the genome that are read less often by the cost-saving technology. A paper describing the research appeared online April 13 in the journal Scientific Reports.
"Although it was known that coveragethe average number of times a given piece of DNA is read during sequencingcould be uneven in whole-exome sequencing, our new methods are the first to really quantify this," said Santhosh Girirajan, assistant professor of biochemistry and molecular biology and of anthropology at Penn State and an author of the paper. "Adequate coverageoften as many as 70 or more reads for each piece of DNAincreases our confidence that the sequence is accurate, and without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease. In our study, we found 832 genes that have systematically low coverage across three different sequencing platforms, meaning that these genes would be missed in disease studies."
The researchers developed two different methods to identify low-coverage regions in whole-exome sequence data. The first method identifies regions with inconsistent coverage compared to other regions in the genome from multiple samples. The second method calculates the number of low-coverage regions among different samples in the same study. They have packaged both methods into an open-source software for other researchers to use.
"Even when the average coverage in a whole-exome sequencing study was high, some regions appeared to have systematically low-coverage," said Qingyu Wang, a graduate student at Penn State at the time of the research and the first author of the paper.
Low-coverage regions may result from limited precision in whole-exome sequencing technologies due to certain genomic features. Highly-repetitive stretches of DNAregions of the genome where the same simple sequence of As, Ts, Cs and Gs can be repeated many timescan prevent the sequencer from reading the DNA properly. Indeed, the study showed that at least 60 percent of low-coverage genes occur near DNA repeats. As an example, the gene MAST4 contains a repeated sequence element that leads to a three-fold reduction in coverage compared to non-repeating sequences. Even when other genes have sufficient coverage, this region of the MAST4 gene falls well below the recommended coverage to detect genetic variations in these studies.
"One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes," said Girirajan. "Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome. However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies."
Explore further: Whole genome or exome sequencing: An individual insight
More information: Qingyu Wang et al. Novel metrics to measure coverage in whole exome sequencing datasets reveal local and global non-uniformity, Scientific Reports (2017). DOI: 10.1038/s41598-017-01005-x
Focusing on parts rather than the whole, when it comes to genome sequencing, might be extremely useful, finds research in BioMed Central's open access journal Genome Medicine. The research compares several sequencing technologies ...
(Medical Xpress)An international team of researchers has developed a way to use RNA sequencing to help in diagnosing patients with rare genetic muscle conditions. In their paper published in the journal Science Translational ...
Researchers have analysed 44 exome datasets from four different testing kits and shown that they missed a high proportion of clinically relevant regions. At least one gene in each exome method was missing more than 40 percent ...
UCLA researchers have found that a state-of-the-art molecular genetic test greatly improves the speed and accuracy with which they can diagnose neurogenetic disorders in children and adults. The discovery could lead directly ...
Published in today's edition of Nature, the research led by Dr Monkol Lek of the University of Sydney and Dr Daniel MacArthur of The Broad Institute of MIT and Harvard Universities reveals patterns of genetic variation worldwide ...
A new study that assesses the accuracy of modern human-genome-sequencing technologies found that some medically significant portions of an individual's DNA blueprint are situated in complex, hard-to-analyze regions that are ...
Whole-exome DNA sequencinga technology that saves time and money by sequencing only protein-coding regions and not the entire genomemay routinely miss detecting some genetic variations associated with disease, according ...
Research published this week in Scientific Reports uses computer image and statistical shape analysis to shed light on which parts of the face are most likely to be inherited.
Salk scientists and collaborators have shed light on a long-standing question about what leads to variation in stem cells by comparing induced pluripotent stem cells (iPSCs) derived from identical twins. Even iPSCs made from ...
In a study published today in PLoS ONE, a team of researchers reports solving a medical mystery in a day's work. In record-time detective work, the scientists narrowed down the genetic cause of intellectual disability in ...
After nearly 40 years of searching, Johns Hopkins researchers report they have identified a part of the human genome that appears to block an RNA responsible for keeping only a single X chromosome active when new female embryos ...
It's not so hard anymore to find genetic variations in patients, said Brown University genomics expert William Fairbrother, but it remains difficult to understand whether and how those mutations undermine health.
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
Originally posted here:
Disease-associated genes routinely missed in some genetic studies - Medical Xpress
- Copy number variation of the restorer Rf4 underlies human selection ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- NYU Langone Health in the NewsThursday, November 9, 2023 - NYU Langone Health - November 15th, 2023 [November 15th, 2023]
- Eugenics: Plaguing scientific community with dark history | Opinion ... - The Arkansas Traveler - November 15th, 2023 [November 15th, 2023]
- Cranberries can bounce, float and pollinate themselves: The saucy ... - Japan Today - November 15th, 2023 [November 15th, 2023]
- Government Housing Assistance Linked to Increased Cancer ... - HealthDay - November 15th, 2023 [November 15th, 2023]
- Rate of New Lung Cancer Cases Has Decreased Over Last Five Years - HealthDay - November 15th, 2023 [November 15th, 2023]
- Clinically relevant antibiotic resistance genes are linked to a limited ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- Disparities in Guideline-Concordant Care Found for Black CRC ... - HealthDay - November 15th, 2023 [November 15th, 2023]
- Mathematician Heather Harrington is new director at the Max Planck ... - EurekAlert - November 15th, 2023 [November 15th, 2023]
- New study finds genetic testing can effectively identify patients with ... - EurekAlert - November 15th, 2023 [November 15th, 2023]
- STK11 loss leads to YAP1-mediated transcriptional activation in ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- CRISPR-broad: combined design of multi-targeting gRNAs and ... - Nature.com - November 15th, 2023 [November 15th, 2023]
- Master regulator of the dark genome greatly improves cancer T-cell ... - Science Daily - November 15th, 2023 [November 15th, 2023]
- Omega Therapeutics Showcases Bidirectional and Multiplexed ... - BioSpace - November 15th, 2023 [November 15th, 2023]
- Today is International 15q Day - ASBMB Today - November 15th, 2023 [November 15th, 2023]
- Evolution of taste: Sharks were already able to perceive bitter ... - EurekAlert - November 15th, 2023 [November 15th, 2023]
- Stanford Scientists Uncover New Indicators of Health, Disease, and ... - SciTechDaily - October 16th, 2023 [October 16th, 2023]
- NHGRI Director Eric Green elected to the National Academy of ... - National Human Genome Research Institute - October 16th, 2023 [October 16th, 2023]
- Monkey survives for two years after gene-edited pig-kidney transplant - Nature.com - October 16th, 2023 [October 16th, 2023]
- Opinion: Interest in RNA Editing Accelerates as Therapies Approach ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- Regulation of dermal fibroblasts by human neutrophil peptides ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Consistent effects of the genetics of happiness across the lifespan ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Storytelling through the looking glass of genetics The Stute - The Stute - October 16th, 2023 [October 16th, 2023]
- Pet dogs shed light on human health, researchers say - UPI News - October 16th, 2023 [October 16th, 2023]
- Native microbiome dominates over host factors in shaping the ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Illinois-led project to sequence soybean genomes, improve future ... - Herald-Whig - October 16th, 2023 [October 16th, 2023]
- Unrealized targets in the discovery of antibiotics for Gram-negative ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- How Biotech And AI Are Transforming The Human - Noema Magazine - October 16th, 2023 [October 16th, 2023]
- The Many Lives of Alexandria Forbes - BioSpace - October 16th, 2023 [October 16th, 2023]
- CEP20 promotes invasion and metastasis of non-small cell lung ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Genotyping, sequencing and analysis of 140,000 adults from Mexico ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- The role and impact of alternative polyadenylation and miRNA ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Human - Simple English Wikipedia, the free encyclopedia - January 30th, 2023 [January 30th, 2023]
- Deep Dive Ties Together Dog Genetics, Brain Physiology and Behavior to Explain Why Collies Are Different from Terriers - Scientific American - December 12th, 2022 [December 12th, 2022]
- How oxytocin drives connections of newly integrated adult-born neurons: Research - Hindustan Times - December 12th, 2022 [December 12th, 2022]
- Alzheimer's Disease Genetics Fact Sheet - National Institute on Aging - December 2nd, 2022 [December 2nd, 2022]
- Human genetic clustering - Wikipedia - November 23rd, 2022 [November 23rd, 2022]
- Human Genome Project Fact Sheet - November 23rd, 2022 [November 23rd, 2022]
- Abstracts | International Congress of Human Genetics 2023 - November 23rd, 2022 [November 23rd, 2022]
- Ancient DNA and Neanderthals | The Smithsonian Institution's Human ... - November 16th, 2022 [November 16th, 2022]
- Biological Influences on Human Behavior: Genetics & Environment - November 16th, 2022 [November 16th, 2022]
- Fluent BioSciences showcasing breakthrough solutions to enable unprecedented scale, cost-efficiency and access for single-cell RNA sequencing at the... - October 28th, 2022 [October 28th, 2022]
- Human behaviour genetics - Wikipedia - October 23rd, 2022 [October 23rd, 2022]
- Nucleome Therapeutics raises oversubscribed 37.5 million Series A financing to decode the dark matter of the human genome and deliver first-in-class... - October 19th, 2022 [October 19th, 2022]
- Gladstone data scientist elected to the National Academy of Medicine - EurekAlert - October 19th, 2022 [October 19th, 2022]
- Ocugen to Host R&D Day in New York City on Tuesday, November 1, 2022 - Yahoo Finance - October 19th, 2022 [October 19th, 2022]
- Pharmacy researcher earns $2.3 million NIH award to study opioid addiction - EurekAlert - October 19th, 2022 [October 19th, 2022]
- Study shows age often plays a bigger role than genetics in gene expression and susceptibility to disease - Anti Aging News - October 19th, 2022 [October 19th, 2022]
- CSRWire - Direct Relief, Amgen and C/Can Team Up To Improve Access to Breast Cancer Diagnostics and Treatment in Paraguay - CSRwire.com - October 19th, 2022 [October 19th, 2022]
- Maze Therapeutics Appoints Harold Bernstein, M.D., Ph.D., as President, Research and Development and Chief Medical Officer - Business Wire - October 19th, 2022 [October 19th, 2022]
- New Rare Disease Therapy Effectively Lowers Plasma Phe in Patients with PKU - MD Magazine - October 19th, 2022 [October 19th, 2022]
- GSK : announces expanded collaboration with Tempus in precision medicine to accelerate R&D - Marketscreener.com - October 19th, 2022 [October 19th, 2022]
- Famous Scientific Discoveries That Changed the Course of History - 24/7 Wall St. - October 19th, 2022 [October 19th, 2022]
- Construction workers seek fulfilment of their demands - Star of Mysore - October 19th, 2022 [October 19th, 2022]
- Genetics | The Smithsonian Institution's Human Origins Program - October 13th, 2022 [October 13th, 2022]
- Genetics - Wikipedia - October 13th, 2022 [October 13th, 2022]
- Study looking at human genetics and Covid vaccine immune responses - Science Media Centre - October 13th, 2022 [October 13th, 2022]
- ASHG 2022 in Los Angeles brings together researchers from around the world to advance discoveries in genetics, genomics research - EurekAlert - October 13th, 2022 [October 13th, 2022]
- Maze Therapeutics Appoints Harold Bernstein, M.D., Ph.D., as President, Research and Development and Chief Medical Officer - Yahoo Finance - October 13th, 2022 [October 13th, 2022]
- The Age of the Pangenome Dawns - DNA Science - PLOS - October 13th, 2022 [October 13th, 2022]
- Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome - Nature.com - October 13th, 2022 [October 13th, 2022]
- Genome editing technologies: final conclusions of the re-examination of Article 13 of the Oviedo Convention - Council of Europe - October 13th, 2022 [October 13th, 2022]
- Global Biobank Meta-analysis Initiative making genome-wide association studies more diverse and representative - EurekAlert - October 13th, 2022 [October 13th, 2022]
- New NHS genetic testing service could save thousands of children in England - The Guardian - October 13th, 2022 [October 13th, 2022]
- Covid protection may be boosted by genes, study shows - Yahoo News Australia - October 13th, 2022 [October 13th, 2022]
- Genomics in Cancer Care Market is estimated to be US$ 72.61 billion by 2032 with a CAGR of 16.3% during the forecast period 2032 - By PMI -... - October 13th, 2022 [October 13th, 2022]
- Identification of hub genes and candidate herbal treatment in obesity through integrated bioinformatic analysis and reverse network pharmacology |... - October 13th, 2022 [October 13th, 2022]
- Our *Homo sapiens* ancestors shared the world with Neanderthals, Denisovans and other types of humans whose DNA lives on in our genes -... - October 8th, 2022 [October 8th, 2022]
- Blue Eyed People Have a Single Ancestor | History of Yesterday - History of Yesterday - October 6th, 2022 [October 6th, 2022]
- Heart infection could be cause of death of Polish, US hero - ABC News - October 6th, 2022 [October 6th, 2022]
- 23andMe Announces Trials-in-Progress Poster Presentation on 23ME-00610, An Investigational Antibody Targeting CD200R1, at The Society for... - October 6th, 2022 [October 6th, 2022]
- The Genetic Drivers Of Longevity In Mice, Humans And Worms - Science 2.0 - October 6th, 2022 [October 6th, 2022]
- ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma | Communications Biology - Nature.com - October 6th, 2022 [October 6th, 2022]
- 'Neanderthal Man' Nobel Prize winner Svante Pbo revolutionized anthropology. Here is a look back at his groundbreaking 2014 memoir - Genetic Literacy... - October 6th, 2022 [October 6th, 2022]
- Understanding Human Genetic Variation - NCBI Bookshelf - September 14th, 2022 [September 14th, 2022]
- Genetics - National Institute of General Medical Sciences (NIGMS) - September 14th, 2022 [September 14th, 2022]
- People with ME invited to take part in major genetic study - The Independent - September 14th, 2022 [September 14th, 2022]
- Ketamine Promising for Rare Condition Linked to Autism - Medscape - September 14th, 2022 [September 14th, 2022]
- How a small, unassuming fish helps reveal gene adaptations - University of Wisconsin-Madison - September 14th, 2022 [September 14th, 2022]
- How Nutrigenomics Explores Links Between Nutrition And Genes - Health Digest - September 14th, 2022 [September 14th, 2022]