Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility
Using Oxford Nanopore sequencing, Gong, Sun and Wang et al. identified 111,288 SVs in 945 Han Chinese individuals. Oxford Nanopore technology allowed for precise breakpoint mapping and haplotype resolution, enabling the detection of large, complex SVs. This study provides valuable insights into human genetic diversity and how this connects to disease risk, genetic traits, and ancient human ancestry.
Key points:
Oxford Nanopore sequencing surpassed the capabilities of short-read sequencing in detecting complex variants — over 87,000 novel SVs were identified in this study that were missed in the gnomAD project (a high-coverage short-read dataset from nearly 15,000 individuals)
24.56% of the SVs discovered here had not been documented in previous long- or short-read datasets
Oxford Nanopore sequencing captured large, complex SVs affecting gene function, enhancers, and regulatory elements
The authors identified a variant in GSDMD linked to bone mineral density and kidney injury risk, and another in WWP2 associated with height, fat distribution, and immunity
The authors used multiple long- and short-read datasets to study the Han diversity in a global and evolutionary context. Approximately 2% of their SVs are ancient polymorphisms shared with chimpanzees, and 5% are shared with Neanderthals and Denisovans, shedding light on evolutionary history
Sample type: human blood