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在 338963 个人类中发现了全基因组串联重复扩展的范围。

A genome-wide spectrum of tandem repeat expansions in 338,963 humans.

机构信息

Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.

Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.

出版信息

Cell. 2024 Apr 25;187(9):2336-2341.e5. doi: 10.1016/j.cell.2024.03.004. Epub 2024 Apr 5.

Abstract

The Genome Aggregation Database (gnomAD), widely recognized as the gold-standard reference map of human genetic variation, has largely overlooked tandem repeat (TR) expansions, despite the fact that TRs constitute ∼6% of our genome and are linked to over 50 human diseases. Here, we introduce the TR-gnomAD (https://wlcb.oit.uci.edu/TRgnomAD), a biobank-scale reference of 0.86 million TRs derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries (39.5% non-European samples). TR-gnomAD offers critical insights into ancestry-specific disease prevalence using disparities in TR unit number frequencies among ancestries. Moreover, TR-gnomAD is able to differentiate between common, presumably benign TR expansions, which are prevalent in TR-gnomAD, from those potentially pathogenic TR expansions, which are found more frequently in disease groups than within TR-gnomAD. Together, TR-gnomAD is an invaluable resource for researchers and physicians to interpret TR expansions in individuals with genetic diseases.

摘要

基因组聚集数据库(gnomAD)被广泛认为是人类遗传变异的黄金标准参考图谱,但它在很大程度上忽略了串联重复(TR)扩展,尽管 TR 构成了我们基因组的约 6%,并且与 50 多种人类疾病有关。在这里,我们引入了 TR-gnomAD(https://wlcb.oit.uci.edu/TRgnomAD),这是一个基于生物库的参考数据库,包含了来自 338963 个具有不同祖先的全基因组测序(WGS)样本的 0.86 百万个 TR(39.5%的非欧洲样本)。TR-gnomAD 利用不同祖先之间 TR 单位数量频率的差异,提供了关于特定祖先疾病流行率的关键见解。此外,TR-gnomAD 能够区分常见的、推测为良性的 TR 扩展,这些扩展在 TR-gnomAD 中很常见,以及那些潜在致病性的 TR 扩展,这些扩展在疾病组中比在 TR-gnomAD 中更常见。总之,TR-gnomAD 是研究人员和医生解释遗传疾病个体中 TR 扩展的宝贵资源。

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本文引用的文献

1
A deep population reference panel of tandem repeat variation.
Nat Commun. 2023 Oct 23;14(1):6711. doi: 10.1038/s41467-023-42278-3.
2
Characterization of genome-wide STR variation in 6487 human genomes.
Nat Commun. 2023 Apr 12;14(1):2092. doi: 10.1038/s41467-023-37690-8.
3
Recurrent repeat expansions in human cancer genomes.
Nature. 2023 Jan;613(7942):96-102. doi: 10.1038/s41586-022-05515-1. Epub 2022 Dec 14.
4
High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios.
Cell. 2022 Sep 1;185(18):3426-3440.e19. doi: 10.1016/j.cell.2022.08.004.
5
The Research Program: Data quality, utility, and diversity.
Patterns (N Y). 2022 Aug 12;3(8):100570. doi: 10.1016/j.patter.2022.100570.
6
The sequences of 150,119 genomes in the UK Biobank.
Nature. 2022 Jul;607(7920):732-740. doi: 10.1038/s41586-022-04965-x. Epub 2022 Jul 20.
8
Exome sequencing and analysis of 454,787 UK Biobank participants.
Nature. 2021 Nov;599(7886):628-634. doi: 10.1038/s41586-021-04103-z. Epub 2021 Oct 18.
9
30 years of repeat expansion disorders: What have we learned and what are the remaining challenges?
Am J Hum Genet. 2021 May 6;108(5):764-785. doi: 10.1016/j.ajhg.2021.03.011. Epub 2021 Apr 2.
10
Fast identification of differential distributions in single-cell RNA-sequencing data with waddR.
Bioinformatics. 2021 Oct 11;37(19):3204-3211. doi: 10.1093/bioinformatics/btab226.

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