Hattori Atsushi, Fukami Maki
Cytogenet Genome Res. 2020;160(4):167-176. doi: 10.1159/000507837. Epub 2020 May 9.
During gametogenesis, the human genome can acquire various de novo rearrangements. Most constitutional genomic rearrangements are created through 1 of the 4 well-known mechanisms, i.e., nonallelic homologous recombination, erroneous repair after double-strand DNA breaks, replication errors, and retrotransposition. However, recent studies have identified 2 types of extremely complex rearrangements that cannot be simply explained by these mechanisms. The first type consists of chaotic structural changes in 1 or a few chromosomes that result from "chromoanagenesis (an umbrella term that covers chromothripsis, chromoanasynthesis, and chromoplexy)." The other type is large independent rearrangements in multiple chromosomes indicative of "transient multifocal genomic crisis." Germline chromoanagenesis (chromothripsis) likely occurs predominantly during spermatogenesis or postzygotic embryogenesis, while multifocal genomic crisis appears to be limited to a specific time window during oogenesis and early embryogenesis or during spermatogenesis. This review article introduces the current understanding of the molecular basis of de novo rearrangements in the germline.
在配子发生过程中，人类基因组可获得各种新生重排。大多数先天性基因组重排是通过4种已知机制之一产生的，即非等位基因同源重组、双链DNA断裂后的错误修复、复制错误和逆转座。然而，最近的研究发现了2种极其复杂的重排类型，这些重排无法简单地用这些机制来解释。第一种类型是由“染色体发生（一个涵盖染色体碎裂、染色体合成和染色体错乱的统称）”导致的一条或几条染色体的混乱结构变化。另一种类型是多条染色体中的大型独立重排，表明存在“瞬时多灶性基因组危机”。种系染色体发生（染色体碎裂）可能主要发生在精子发生或合子后胚胎发生过程中，而多灶性基因组危机似乎仅限于卵子发生和早期胚胎发生期间或精子发生期间的特定时间窗口。本文综述介绍了目前对种系新生重排分子基础的理解。
