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人类卵母细胞和胚胎中重组及染色体分离的全基因组图谱显示了对母体重组率的选择。

Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates.

作者信息

Ottolini Christian S, Newnham Louise, Capalbo Antonio, Natesan Senthilkumar A, Joshi Hrishikesh A, Cimadomo Danilo, Griffin Darren K, Sage Karen, Summers Michael C, Thornhill Alan R, Housworth Elizabeth, Herbert Alex D, Rienzi Laura, Ubaldi Filippo M, Handyside Alan H, Hoffmann Eva R

机构信息

The Bridge Centre, London, UK.

School of Biosciences, University of Kent, Canterbury, UK.

出版信息

Nat Genet. 2015 Jul;47(7):727-735. doi: 10.1038/ng.3306. Epub 2015 May 18.

Abstract

Crossover recombination reshuffles genes and prevents errors in segregation that lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Here we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses. Genotyping >4 million informative SNPs from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns of 529 chromosome pairs. We uncover a new reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germ line by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings show that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II.

摘要

交叉重组重新排列基因,并防止人类卵子中染色体分离错误导致染色体数目异常(非整倍体),这是妊娠失败和先天性疾病的主要原因。在这里,我们通过回收单个雌性减数分裂的所有三个产物,生成了全基因组交叉和染色体分离模式图谱。对来自23个完整减数分裂的超过400万个信息性单核苷酸多态性(SNP)进行基因分型,使我们能够绘制出2032个母本和1342个父本交叉点,并推断出529对染色体的分离模式。我们发现了一种新的反向染色体分离模式,即两个同源染色体在减数分裂I时分离其姐妹染色单体;通过消除非整倍体胚胎检测到雌性生殖系中对更高重组率的选择;并报告了减数分裂II时针对非重组染色单体的染色体驱动。总的来说,我们的研究结果表明,重组不仅影响减数分裂I时的同源染色体分离,还影响减数分裂II时姐妹染色单体的命运。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a376/4770575/2628bc7f121e/emss-63148-f0001.jpg

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