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. 2021 Jun;53(6):779-786.
doi: 10.1038/s41588-021-00865-4. Epub 2021 May 10.

Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits

Doruk Beyter  1 , Helga Ingimundardottir  1 , Asmundur Oddsson  1 , Hannes P Eggertsson  1   2 , Eythor Bjornsson  1   3   4 , Hakon Jonsson  1 , Bjarni A Atlason  1 , Snaedis Kristmundsdottir  1   5 , Svenja Mehringer  6 , Marteinn T Hardarson  1 , Sigurjon A Gudjonsson  1 , Droplaug N Magnusdottir  1 , Aslaug Jonasdottir  1 , Adalbjorg Jonasdottir  1 , Ragnar P Kristjansson  1 , Sverrir T Sverrisson  1 , Guillaume Holley  1 , Gunnar Palsson  1 , Olafur A Stefansson  1 , Gudmundur Eyjolfsson  7 , Isleifur Olafsson  8 , Olof Sigurdardottir  9 , Bjarni Torfason  10   11 , Gisli Masson  1 , Agnar Helgason  1   12 , Unnur Thorsteinsdottir  1   3 , Hilma Holm  1 , Daniel F Gudbjartsson  1   2 , Patrick Sulem  1 , Olafur T Magnusson  1 , Bjarni V Halldorsson  13   14 , Kari Stefansson  15   16
Affiliations

Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits

Doruk Beyter et al. Nat Genet. 2021 Jun.

Abstract

Long-read sequencing (LRS) promises to improve the characterization of structural variants (SVs). We generated LRS data from 3,622 Icelanders and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions). We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association of a rare deletion in PCSK9 with lower low-density lipoprotein (LDL) cholesterol levels, compared to the population average. We also discovered an association of a multiallelic SV in ACAN with height; we found 11 alleles that differed in the number of a 57-bp-motif repeat and observed a linear relationship between the number of repeats carried and height. These results show that SVs can be accurately characterized at the population scale using LRS data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.

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References

    1. Alkan, C., Coe, B. P. & Eichler, E. E. Genome structural variation discovery and genotyping. Nat. Rev. Genet. 12, 363–376 (2011). - PubMed - PMC - DOI
    1. Weischenfeldt, J., Symmons, O., Spitz, F. & Korbel, J. O. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat. Rev. Genet. 14, 125–138 (2013). - PubMed - DOI
    1. Sudmant, P. H. et al. An integrated map of structural variation in 2,504 human genomes. Nature 526, 75–81 (2015). - PubMed - PMC - DOI
    1. Chaisson, M. J. P. et al. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat. Commun. 10, 1784 (2019). - PubMed - PMC - DOI
    1. Zook, J. M. et al. A robust benchmark for detection of germline large deletions and insertions. Nat. Biotechnol. 38, 1347–1355 (2020). - PubMed - DOI - PMC

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