Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
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DOI：
10.1038/s41588-021-00865-4
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发表时间：
2021-05-10
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Beyter, Doruk;Ingimundardottir, Helga;Stefansson, Kari
长读段测序（LRS）有望改善结构变体（SV）的表征。我们从3，622名冰岛人中生成了LRS数据，并确定了每个人的中位数为22，636个SV（中位数为13，353个插入和9，474个缺失）。我们发现了一组133，886个可靠的SV等位基因，并将其输入到166，281个个体中，以探索它们对疾病和其他性状的影响。我们发现了PCSK 9中一种罕见的缺失与低密度脂蛋白（LDL）胆固醇水平的相关性，与人群平均水平相比。我们还发现了一个多等位基因SV在ACAN与高度的关联，我们发现了11个等位基因，不同的57 bp-基序重复的数量，并观察到进行重复的数量和高度之间的线性关系。这些结果表明，可以使用全基因组非靶向方法中的LRS数据在人群规模上准确表征SV，并展示SV如何影响表型。对来自3，622名冰岛人的长读段测序数据的分析确定了一组高置信度的结构变异，并提供了对人类特征和疾病影响的见解。
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.Analysis of long-read sequencing data from 3,622 Icelanders identifies a set of high-confidence structural variants and provides insights into their effect on human traits and diseases.