小年 (2024-04-30 13:46):
#paper genome-wide spectrum of tandem repeat expansions in 338,963 humans. Cell. 2024 Apr 25;187(9):2336-2341.e5. doi: 10.1016/j.cell.2024.03.004. Epub 2024 Apr 5. PMID: 38582080. 在本篇文章中,作者建立了一个名为TR-gnomAD的串联重复(TR)扩增的生物库规模参考数据库,该数据库涵盖了338,963个全基因组测序样本,其中包括39.5%的非欧洲样本。本研究使用了ExpansionHunter和GangSTR两种基因分型工具来增加TR基因分型的覆盖率。TR-gnomAD提供了关于TR单元数量频率差异的洞见,这些差异揭示了特定祖源与疾病风险之间的联系。例如,作者发现特定祖源中TR单元的扩增频率与某些遗传病的流行程度相关联,比如非洲后裔中肌阵挛型营养不良的DMPK基因中的CAG重复扩增较欧洲后裔中的较少。 阅读思考:TR-gnomAD的建立极大地丰富了我们对人类基因组中TR区域多样性的理解,并提供了一种全新的角度来观察遗传疾病与特定人种间的关联。这项研究强调了TR扩增在特定祖源中可能具有的疾病相关性,特别是在ALS、亨廷顿病等超过50种与TR扩增相关的致命性疾病中。此外,该数据库也对临床诊断提供了重要的参考,尤其是在使用TR 单元数差异来预测疾病风险方面。然而,该研究的一个限制是其主要依赖于短读测序数据,可能导致对大的TR扩增区域的等位基因长度估计不足。未来研究需结合长读测序技术,以提供更准确的TR扩增数据,从而更好地服务于遗传疾病的风险评估和诊断。
IF:45.500Q1 Cell, 2024-Apr-25. DOI: 10.1016/j.cell.2024.03.004 PMID: 38582080
A genome-wide spectrum of tandem repeat expansions in 338,963 humans
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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.
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