An integrated map of structural variation in 2,504 human genomes

By Peter Sudmant, Tobias Rausch, E. Gardner, Robert E. Handsaker, Alexej Abyzov, J. Huddleston, Yan Zhang, Kai Ye, Goo Jun, M. H. Fritz and 72 more. Nature, 2015

2,247 citations recorded by the source corpus.

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/c171fee50b8eff8fa8c02fa8df0c485665dc433f

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In Genetics

Citations in the corpus

The landscape of genomic alterations across childhood cancers (2018, neutral): “…of genomic instability rather than cancer-driving events 97 ; next, peaks overlapping within 1 Mb of chromosomal ends were removed, as here sequencing coverage tends to vary frequently; and last, peaks overlapping with copy-number variable regions 98 (regions ranked 1–100) were excluded.”
Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing (2019, neutral): “Therefore, most projects use multiple algorithms to call SVs, then merge the outputs to increase the precision and/or the recall [6, 13 – 15, 17, 24 – 29].”
Settling the score: variant prioritization and Mendelian disease (2017, background): “Although there are far fewer structural variants (that is, between ~5,000 and ~10,000) in a typical human genome 47 than SNVs and small insertions and deletions (indels), their potential for phenotypic impact is disproportionately large because they can disrupt multiple genes, create gene fusions,…”
Structural variant calling: the long and the short of it (2019, background): “Multiple studies have highlighted their role in functional changes across populations [1, 10, 11] and species [12].”
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects (2016, neutral): “Lastly, we recognize that a majority of structural variants (SVs) are not detectable with current genotyping platforms 32 .”
Insights about clonal hematopoiesis from 8,342 mosaic chromosomal alterations (2018, background): “5kb for deletions and ≈36kb for duplications [74]), although this difference is presumably driven in part by detection sensitivity.”