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非交叉基因转换在人类中表现出强烈的GC偏好性和意外的聚类现象。

Non-crossover gene conversions show strong GC bias and unexpected clustering in humans.

作者信息

Williams Amy L, Genovese Giulio, Dyer Thomas, Altemose Nicolas, Truax Katherine, Jun Goo, Patterson Nick, Myers Simon R, Curran Joanne E, Duggirala Ravi, Blangero John, Reich David, Przeworski Molly

机构信息

Department of Biological Sciences, Columbia University, New York, United States.

Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, United States.

出版信息

Elife. 2015 Mar 25;4:e04637. doi: 10.7554/eLife.04637.

Abstract

Although the past decade has seen tremendous progress in our understanding of fine-scale recombination, little is known about non-crossover (NCO) gene conversion. We report the first genome-wide study of NCO events in humans. Using SNP array data from 98 meioses, we identified 103 sites affected by NCO, of which 50/52 were confirmed in sequence data. Overlap with double strand break (DSB) hotspots indicates that most of the events are likely of meiotic origin. We estimate that a site is involved in a NCO at a rate of 5.9 × 10(-6)/bp/generation, consistent with sperm-typing studies, and infer that tract lengths span at least an order of magnitude. Observed NCO events show strong allelic bias at heterozygous AT/GC SNPs, with 68% (58-78%) transmitting GC alleles (p = 5 × 10(-4)). Strikingly, in 4 of 15 regions with resequencing data, multiple disjoint NCO tracts cluster in close proximity (∼20-30 kb), a phenomenon not previously seen in mammals.

摘要

尽管在过去十年里,我们对精细尺度重组的理解取得了巨大进展,但对于非交叉(NCO)基因转换却知之甚少。我们报告了人类中首次全基因组范围的NCO事件研究。利用来自98次减数分裂的单核苷酸多态性(SNP)阵列数据,我们鉴定出103个受NCO影响的位点,其中50/52个在序列数据中得到证实。与双链断裂(DSB)热点的重叠表明,大多数事件可能起源于减数分裂。我们估计一个位点参与NCO的频率为5.9×10^(-6)/bp/世代,这与精子分型研究结果一致,并推断其片段长度至少跨越一个数量级。观察到的NCO事件在杂合的AT/GC SNP处表现出强烈的等位基因偏向性,68%(58 - 78%)传递GC等位基因(p = 5×10^(-4))。引人注目的是,在15个有重测序数据的区域中的4个区域,多个不连续的NCO片段紧密聚集(约20 - 30 kb),这一现象在哺乳动物中此前未见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9f/4404656/78e0fb1cfc95/elife04637f001.jpg

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