小柯机器人

美国安进公司Kari Stefansson、Bjarni V. Halldorsson等研人员合作报道英国生物银行中150,119个基因组的序列。相关论文于2022年7月20日在线发表于国际学术期刊《自然》。

研究人员报道了对英国生物银行中150,119人的全基因组测序的分析。这构成了一套高质量的变体，包括585,040,410个单核苷酸多态性，占所有可能的人类单核苷酸多态性的7.0%，以及58,707,036个不连贯性。这一大组变体使研究人员能够通过对基因组上的窗口进行耗竭等级评分，从而描述基于种群内序列变异的选择特征。耗竭等级分析表明，编码外显子代表了基因组中受强序列保护的一小部分区域。研究人员在英国生物银行中定义了三个队列：一个大型英国爱尔兰队列，一个较小的非洲队列和一个南亚队列。

研究人员提供了一个单倍型参考板，可以对三个或更多被测序个体携带的大多数变异体进行可靠的归纳。研究人员确定了895,055个结构变体和2,536,688个微卫星，这些变体组通常被排除在大规模全基因组测序研究之外。利用这个强大的新资源，研究人员提供了几个例子，说明罕见变体的性状关联，其影响之大是以前基于全外显子组测序和/或推算的研究所没有发现的。

据悉，关于人类基因组序列的多样性如何影响表型多样性的详细知识，取决于对序列和表型变异的全面和可靠的特征描述。在过去的十年中，对这种关系的深入了解是通过全外显子组测序，或具有丰富表型数据的大群组的全基因组测序获得的。

附：英文原文

Title: The sequences of 150,119 genomes in the UK Biobank

Author: Halldorsson, Bjarni V., Eggertsson, Hannes P., Moore, Kristjan H. S., Hauswedell, Hannes, Eiriksson, Ogmundur, Ulfarsson, Magnus O., Palsson, Gunnar, Hardarson, Marteinn T., Oddsson, Asmundur, Jensson, Brynjar O., Kristmundsdottir, Snaedis, Sigurpalsdottir, Brynja D., Stefansson, Olafur A., Beyter, Doruk, Holley, Guillaume, Tragante, Vinicius, Gylfason, Arnaldur, Olason, Pall I., Zink, Florian, Asgeirsdottir, Margret, Sverrisson, Sverrir T., Sigurdsson, Brynjar, Gudjonsson, Sigurjon A., Sigurdsson, Gunnar T., Halldorsson, Gisli H., Sveinbjornsson, Gardar, Norland, Kristjan, Styrkarsdottir, Unnur, Magnusdottir, Droplaug N., Snorradottir, Steinunn, Kristinsson, Kari, Sobech, Emilia, Jonsson, Helgi, Geirsson, Arni J., Olafsson, Isleifur, Jonsson, Palmi, Pedersen, Ole Birger, Erikstrup, Christian, Brunak, Sren, Ostrowski, Sisse Rye, Thorleifsson, Gudmar, Jonsson, Frosti, Melsted, Pall, Jonsdottir, Ingileif, Rafnar, Thorunn, Holm, Hilma, Stefansson, Hreinn, Saemundsdottir, Jona, Gudbjartsson, Daniel F., Magnusson, Olafur T., Masson, Gisli, Thorsteinsdottir, Unnur, Helgason, Agnar, Jonsson, Hakon, Sulem, Patrick, Stefansson, Kari

Issue&Volume: 2022-07-20

Abstract: Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data1,2. Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank3. This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation. To measure selection on variants, whole-genome sequencing of approximately 150,000 individuals from the UK Biobank is used to rank sequence variants by their level of depletion.

DOI: 10.1038/s41586-022-04965-x

Source: https://www.nature.com/articles/s41586-022-04965-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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