小柯机器人

解码遗传学/安进公司Kari Stefansson研究组取得一项新成果。他们对3,622名冰岛人进行了长读测序（LRS），由此提供了洞察结构变异（SV）在人类疾病和其他性状中作用的见解。这一研究成果于2021年5月10日发表在国际顶尖学术期刊《自然-遗传学》杂志上。

他们从3,622名冰岛人生成了LRS数据，并确定了每个人22,636个SV的中位数（13,353个插入和9,474个缺失的中位数）。他们发现了133,886个可靠的基因分型SV等位基因，并将其推算为166,281个个体，以研究其对疾病和其他特征的影响。他们发现与群体平均水平相比，PCSK9中罕见的缺失与较低的低密度脂蛋白（LDL）胆固醇水平相关。他们还发现了ACAN中多等位基因SV与身高的关联。

他们发现了11个等位基因，每个等位基因的57-bp-基序重复次数不同，并且观察到的重复次数与身高之间呈线性关系。这些结果表明，可以使用LRS数据以全基因组范围的非靶向方法在群体规模上准确表征SV，并证明SV如何影响表型。

附：英文原文

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

Author: Doruk Beyter, Helga Ingimundardottir, Asmundur Oddsson, Hannes P. Eggertsson, Eythor Bjornsson, Hakon Jonsson, Bjarni A. Atlason, Snaedis Kristmundsdottir, Svenja Mehringer, Marteinn T. Hardarson, Sigurjon A. Gudjonsson, Droplaug N. Magnusdottir, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Ragnar P. Kristjansson, Sverrir T. Sverrisson, Guillaume Holley, Gunnar Palsson, Olafur A. Stefansson, Gudmundur Eyjolfsson, Isleifur Olafsson, Olof Sigurdardottir, Bjarni Torfason, Gisli Masson, Agnar Helgason, Unnur Thorsteinsdottir, Hilma Holm, Daniel F. Gudbjartsson, Patrick Sulem, Olafur T. Magnusson, Bjarni V. Halldorsson, Kari Stefansson

Issue&Volume: 2021-05-10

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. 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.

DOI: 10.1038/s41588-021-00865-4

Source: https://www.nature.com/articles/s41588-021-00865-4

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