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完整的人类重组图谱。

Complete human recombination maps.

作者信息

Palsson Gunnar, Hardarson Marteinn T, Jonsson Hakon, Steinthorsdottir Valgerdur, Stefansson Olafur A, Eggertsson Hannes P, Gudjonsson Sigurjon A, Olason Pall I, Gylfason Arnaldur, Masson Gisli, Thorsteinsdottir Unnur, Sulem Patrick, Helgason Agnar, Gudbjartsson Daniel F, Halldorsson Bjarni V, Stefansson Kari

机构信息

deCODE genetics/Amgen Inc., Reykjavik, Iceland.

School of Technology, Reykjavik University, Reykjavík, Iceland.

出版信息

Nature. 2025 Mar;639(8055):700-707. doi: 10.1038/s41586-024-08450-5. Epub 2025 Jan 22.

Abstract

Human recombination maps are a valuable resource for association and linkage studies and crucial for many inferences of population history and natural selection. Existing maps are based solely on cross-over (CO) recombination, omitting non-cross-overs (NCOs)-the more common form of recombination-owing to the difficulty in detecting them. Using whole-genome sequence data in families, we estimate the number of NCOs transmitted from parent to offspring and derive complete, sex-specific recombination maps including both NCOs and COs. Mothers have fewer but longer NCOs than fathers, and oocytes accumulate NCOs in a non-regulated fashion with maternal age. Recombination, primarily NCO, is responsible for 1.8% (95% confidence interval: 1.3-2.3) and 11.3% (95% confidence interval: 9.0-13.6) of paternal and maternal de novo mutations, respectively, and may drive the increase in de novo mutations with maternal age. NCOs are substantially more prominent than COs in centromeres, possibly to avoid large-scale genomic changes that may cause aneuploidy. Our results demonstrate that NCOs highlight to a much greater extent than COs the differences in the meiotic process between the sexes, in which maternal NCOs may reflect the safeguarding of oocytes from infancy until ovulation.

摘要

人类重组图谱是关联研究和连锁研究的宝贵资源,对于许多群体历史和自然选择的推断至关重要。现有的图谱仅基于交叉(CO)重组构建,由于检测非交叉(NCO)重组(更常见的重组形式)存在困难,故而将其忽略。利用家族中的全基因组序列数据,我们估算了从亲代传递给子代的NCO数量,并绘制出完整的、按性别区分的包含NCO和CO的重组图谱。母亲的NCO数量较少但长度更长,且随着母亲年龄增长,卵母细胞以无规律的方式积累NCO。重组(主要是NCO)分别占父源和母源新生突变的1.8%(95%置信区间:1.3 - 2.3)和11.3%(95%置信区间:9.0 - 13.6),并且可能促使新生突变随母亲年龄增加。在着丝粒区域,NCO比CO显著得多,这可能是为了避免可能导致非整倍体的大规模基因组变化。我们的结果表明,与CO相比,NCO在更大程度上凸显了两性减数分裂过程的差异,其中母源NCO可能反映了从婴儿期到排卵期间卵母细胞的保护机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c6d/11922761/c0ee7a9b5416/41586_2024_8450_Fig1_HTML.jpg

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