Structural variants in Chinese population and their impact on phenotypes, diseases and population adaptation

Abstract

A complete characterization of genetic variation is a fundamental goal of human genome research. Long-read sequencing (LRS) improves the sensitivity for structural variant (SV) discovery and facilitates a better understanding of the SV spectrum in human genomes. Here, we conduct the first LRS-based SV analysis in Chinese population. We perform whole-genome LRS for 405 unrelated Chinese, with 68 phenotypic and clinical measurements. We discover a complex landscape of 132,312 non-redundant SVs, of which 53.3% are novel. The identified SVs are of high-quality validated by the PacBio high-fidelity sequencing and PCR experiments. The total length of SVs represents approximately 13.2% of the human reference genome. We annotate 1,929 loss-of-function SVs affecting the coding sequences of 1,681 genes. We discover new associations of SVs with phenotypes and diseases, such as rare deletions in HBA1/HBA2/HBB associated with anemia and common deletions in GHR associated with body height. Furthermore, we identify SV candidates related to human immunity that differentiate sub-populations of Chinese. Our study reveals the complex landscape of human SVs in unprecedented detail and provides new insights into their roles contributing to phenotypes, diseases and evolution. The genotypic and phenotypic resource is freely available to the scientific community.

Pangenome obtained by long-read sequencing of 11 genomes reveal hidden functional structural variants in pigs

“…Here, we focus on simple SVs (DELs, DUPs, INSs, and INVs), so the reads mapping method was applied as used in other studies. 22 , 75 …”

“… 17 Numerous studies have implicated SVs in human diseases, 18 , 19 e.g., autism, cancer, and high-altitude hypoxia adaptation in the Tibetan population and body weight adaptation. 20 , 21 , 22 A comprehensive set of SVs has been identified to be associated with key phenotypic traits in diverse plants and animals, including kernel weight in maize, 23 fruit shape, fruit flavor, flowering, and fertility in tomato, 24 production in soybean, 9 fruit maturity and shape in peach, 25 the dominance of a white or patch coat in European domestic pigs, 26 white coat color in sheep 27 and water buffalo, 28 color sidedness in cattle. 29 However, these studies have only deciphered a small set of SVs that contribute to complex traits in plants and animals because SVs have not been fully and accurately discovered, particularly in animals, owing to the limitations of BeadChip or SRS.…”

Comprehensive analysis of structural variants in chickens using PacBio sequencing

“…Structural variants (SVs) are rearrangements larger than 50 bp in chromosomes ( Alkan et al, 2011 ). Several SVs have been associated with phenotypic variation ( Wright et al, 2009 ; Imsland et al, 2012 ; Dorshorst et al, 2015 ; Guo et al, 2016 ; Chen et al, 2017 ; Bertolotti et al, 2020 ; Wu et al, 2021 ), productive traits ( Liu et al, 2010 ; Zhao et al, 2016 ; Liu et al, 2019 ), immune function, and disease resistance ( Luo et al, 2013 ; Bickhart and Liu, 2014 ) in animals.…”

Evaluation of Germline Structural Variant Calling Methods for Nanopore Sequencing Data

“…Long-read sequencing from Pacific Biosciences and Oxford Nanopore Technologies (ONT) has emerged in recent years ( Chaisson et al, 2015 ; Jain et al, 2016 ) and proved invaluable in identifying previously intractable DNA sequences ( Li and Freudenberg, 2014 ; Bolognini et al, 2020 ) and close gaps in the human genome assemblies and unraveling otherwise undetected SVs at population-scale ( Beyter et al, 2020 ; Wu et al, 2021 ).…”