小柯机器人

美国布里格姆妇女医院和哈佛医学院Po-Ru Loh和麻省理工学院博德研究所Steven A. McCarroll课题组合作发现，重复多态性是青光眼和结直肠癌最高遗传风险位点的基础。2023年7月31日，国际知名学术期刊《细胞》发表了这一成果。

为了评估串联重复序列(VNTRs)在全基因组范围内的表型影响，他们采用统计归算方法估计了418,136名英国生物库参与者和838名GTEx参与者的9,561个常染色体VNTR位点的长度。关联和统计精细定位分析确定了58个VNTRs，这些VNTRs似乎影响了UK Biobank中的一个复杂特征，其中18个VNTRs似乎也调节了附近基因的表达或剪接。

TMCO1和EIF3H上的非编码VNTRs似乎分别对青光眼和结直肠癌风险的常见人类遗传变异产生了最大的已知贡献。这两个VNTR中的每一个都与个体的风险范围>2倍相关。这些结果揭示了非编码VNTRs在人类健康和基因调控中的重要作用。

据了解，由于VNTR的数量不同，人类基因组的许多区域在个体之间的长度不同。

附：英文原文

Title: Repeat polymorphisms underlie top genetic risk loci for glaucoma and colorectal cancer

Author: Ronen E. Mukamel, Robert E. Handsaker, Maxwell A. Sherman, Alison R. Barton, Margaux L.A. Hujoel, Steven A. McCarroll, Po-Ru Loh

Issue&Volume: 2023-07-31

Abstract: Many regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). To assess the phenotypic impact of VNTRs genome-wide, we applied a statistical imputation approach to estimate the lengths of 9,561 autosomal VNTR loci in 418,136 unrelated UK Biobank participants and 838 GTEx participants. Association and statistical fine-mapping analyses identified 58 VNTRs that appeared to influence a complex trait in UK Biobank, 18 of which also appeared to modulate expression or splicing of a nearby gene. Non-coding VNTRs at TMCO1 and EIF3H appeared to generate the largest known contributions of common human genetic variation to risk of glaucoma and colorectal cancer, respectively. Each of these two VNTRs associated with a >2-fold range of risk across individuals. These results reveal a substantial and previously unappreciated role of non-coding VNTRs in human health and gene regulation.

DOI: 10.1016/j.cell.2023.07.002

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00735-3