目的:回顾染色体的发现并分析其对人类生殖的影响。
方法:数据库和文献分析。
方法:大学医院。
方法:大量复杂染色体重排的载体。
方法:细胞遗传学分析和分子检测(荧光原位杂交,微阵列,全基因组测序)。
方法:在人类配子和着床前胚胎中发生染色体增多症,关于文献中描述的潜在致病机制。
结果:检索数据库中截至2014年3月发表的文献。嗜铬细胞增多症的特征是一个(或几个)染色体片段的破碎,然后是产生的片段的随意重组,通过单个初始灾难性事件引起的。涉及凋亡失败的几种机制,端粒侵蚀,有丝分裂错误,微核形成,p53失活可能会导致染色体增生。值得注意的是,在人类生殖领域,所有这些合理的机制都已被确定为生殖失败和染色体异常发生的原因。配子发生和早期胚胎发育的特定特征,例如细胞周期和有丝分裂检查点的薄弱以及生殖细胞和早期卵裂胚胎的快速分裂动力学,可能有助于染色体分裂的出现。
结论:这种新的大规模染色体重排的发现极大地改变了我们对复杂基因组重排起源的理解。这篇评论中提供的数据支持这样的假设,即染色体可以在人类种系和早期胚胎发育过程中发挥作用。在配子发生和早期人类胚胎发生中,嗜铬细胞增多可能比以前认为的更频繁。
OBJECTIVE: To
review the discovery of chromothripsis and analyze its impact on human reproduction.
METHODS: Database and literature analysis.
METHODS: University hospital.
METHODS: Carriers of massive and complex chromosomal rearrangements.
METHODS: Cytogenetic analysis and molecular testing (fluorescence in situ hybridization, microarray, whole-genome sequencing).
METHODS: Chromothripsis occurrence in human gametes and preimplantation embryos, with regard to the potential causative mechanisms described in literature.
RESULTS: Databases were searched for the literature published up to March 2014. Chromothripsis is characterized by the shattering of one (or a few) chromosome segments followed by a haphazard reassembly of the fragments generated, arising through a single initial catastrophic event. Several mechanisms involving abortive apoptosis, telomere erosion, mitotic errors, micronuclei formation, and p53 inactivation might cause chromothripsis. The remarkable point is that all these plausible mechanisms have been identified in the field of human reproduction as causal factors for reproductive failures and the genesis of chromosomal abnormalities. Specific features of gametogenesis and early embryonic development such as the weakness of cell cycle and mitosis checkpoints and the rapid kinetics of division in germ cells and early cleavage embryos may contribute to the emergence of chromothripsis.
CONCLUSIONS: The discovery of this new class of massive chromosomal rearrangement has deeply modified our understanding on the genesis of complex genomic rearrangements. Data presented in this
review support the assumption that chromothripsis could operate in human germlines and during early embryonic development. Chromothripsis might arise more frequently than previously thought in both gametogenesis and early human embryogenesis.