deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
Nat Genet. 2021 Jun;53(6):779-786. doi: 10.1038/s41588-021-00865-4. Epub 2021 May 10.
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.
长读测序（LRS）有望改善结构变异（SV）的特征。我们从 3622 名冰岛人身上生成了 LRS 数据，发现每个人的中位数有 22636 个 SV（中位数为 13353 个插入和 9474 个缺失）。我们发现了一组 133886 个可靠的 SV 等位基因，并将其推断到 166281 个人中，以探索它们对疾病和其他特征的影响。我们发现 PCSK9 中的罕见缺失与人群平均水平相比，与较低的低密度脂蛋白（LDL）胆固醇水平相关。我们还发现 ACAN 中的多等位基因 SV 与身高有关；我们发现了 11 个等位基因，其在 57-bp-motif 重复的数量上有所不同，并且发现携带的重复数量与身高之间存在线性关系。这些结果表明，使用 LRS 数据以全基因组非靶向的方法在人群规模上可以准确地描述 SV，并展示了 SV 如何影响表型。
