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Mapping and characterization of structural variation in 17,795 human genomes

التفاصيل البيبلوغرافية
العنوان: Mapping and characterization of structural variation in 17,795 human genomes
المؤلفون: Ryan M. Layer, Susan K. Dutcher, Donna M. Muzny, Krishna L. Kanchi, Eric S. Lander, David E. Larson, Colby Chiang, Nathan O. Stitziel, Michael C. Zody, Tara C. Matise, Ira M. Hall, Allison A. Regier, Catherine Reeves, Haley J. Abel, William J Salerno, Nhgri Centers for Common Disease Genomics, Steven Buyske, Indraniel Das, Benjamin M. Neale
المساهمون: Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Doctoral Programme in Social Sciences, Department of Public Health, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, University Management, Biostatistics Helsinki, HUS Heart and Lung Center, CAMM - Research Program for Clinical and Molecular Metabolism, Helsinki University Hospital Area
المصدر: Nature
بيانات النشر: Springer Science and Business Media LLC, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Male, IMPACT, DATABASE, PREDICTION, NUCLEOTIDE, Quantitative Trait Loci, Population, Gene Dosage, Computational biology, VARIANTS, Biology, Genome, Article, Epigenesis, Genetic, Structural variation, 03 medical and health sciences, 0302 clinical medicine, ELEMENTS, WIDE ASSOCIATION, Humans, Copy-number variation, COMMUNITY-DRIVEN RESOURCE, Indel, education, Alleles, COPY NUMBER VARIATION, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, education.field_of_study, Multidisciplinary, Whole Genome Sequencing, Genome, Human, Racial Groups, Genetic Variation, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, FRAMEWORK, Human genetics, Genetics, Population, Case-Control Studies, Female, Human genome, 3111 Biomedicine, Software, 030217 neurology & neurosurgery
الوصف: Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles. A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline(1)to map and characterize structural variants in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest, to our knowledge, whole-genome-sequencing-based structural variant resource so far. On average, individuals carry 2.9 rare structural variants that alter coding regions; these variants affect the dosage or structure of 4.2 genes and account for 4.0-11.2% of rare high-impact coding alleles. Using a computational model, we estimate that structural variants account for 17.2% of rare alleles genome-wide, with predicted deleterious effects that are equivalent to loss-of-function coding alleles; approximately 90% of such structural variants are noncoding deletions (mean 19.1 per genome). We report 158,991 ultra-rare structural variants and show that 2% of individuals carry ultra-rare megabase-scale structural variants, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and noncoding elements, and reveal trends that relate to element class and conservation. This work will help to guide the analysis and interpretation of structural variants in the era of whole-genome sequencing.
تدمد: 1476-4687
0028-0836
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b8d328d68dc05cae904578ada3a230f
https://doi.org/10.1038/s41586-020-2371-0
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....5b8d328d68dc05cae904578ada3a230f
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14764687
00280836