Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
The Key Laboratory for Reproductive Medicine of Guangdong Province, Guangzhou 510080, China.
G3 (Bethesda). 2023 Apr 11;13(4). doi: 10.1093/g3journal/jkad031.
Recombination is essential for physical attachments and genetic diversity. The Han Chinese population is the largest ethnic group worldwide, therefore, the construction of a genetic map regarding recombination for the population is essential. In this study, 164 and 240 couples who underwent preimplantation genetic testing for monogenic diseases or segmental rearrangement were included in the analysis. Blastocysts and probands from couples who underwent preimplantation genetic testing for monogenic diseases by single nucleotide polymorphism array were included for recombination analysis. The location of recombination was determined from haplotype phase transitions in parent-offspring pairs at loci where the parents were heterozygous. The genetic map for Chinese in vitro fertilization embryos was constructed by the expectation-maximization algorithm with chip-level data. Our results confirmed that homologous recombination occurred more often in maternal chromosomes, and the age effect was more significant in maternal homologous recombination. A total of 6,494 homologous recombination hotspots (32.3%) were identified in genes of Online Mendelian Inheritance in Man. A uniform association between homologous recombination and aneuploidy was not established. In addition, carriers with identified breakpoints of reciprocal translocations were analyzed, and locations of breakpoints were found partly overlapped with homologous recombination hotspots, implying a possible similar mechanism behind both events. This study highlights the significance of constructing a recombination map, which may improve the accuracy of haplotype analysis for preimplantation genetic testing for monogenic diseases. Overlapping locations of translocation and recombination are worthy of further investigation.
重组对于物理附着和遗传多样性至关重要。汉族是世界上最大的族群，因此，构建该人群的遗传重组图谱至关重要。本研究纳入了 164 对和 240 对接受单基因疾病或片段重排的胚胎植入前遗传学检测的夫妇。对接受单基因疾病的胚胎植入前遗传学检测的夫妇的囊胚和先证者进行了单核苷酸多态性芯片的重组分析。在父母为杂合子的基因座上，通过亲子对的单倍型相位转换来确定重组的位置。利用芯片级数据的期望最大化算法构建了中国人体外受精胚胎的遗传图谱。我们的结果证实，同源重组更多地发生在母染色体中，母源同源重组的年龄效应更为显著。在在线孟德尔遗传数据库中鉴定出 6494 个同源重组热点（32.3%）。同源重组与非整倍体之间没有建立起一致的关联。此外，对已识别的相互易位携带者的断点进行了分析，发现断点的位置部分与同源重组热点重叠，这表明这两个事件背后可能存在类似的机制。本研究强调了构建重组图谱的重要性，这可能提高单基因疾病胚胎植入前遗传学检测的单倍型分析的准确性。易位和重组的重叠位置值得进一步研究。
