Ploidy or genome‐wide chromosomal anomalies such as triploidy, diploid/triploid mixoploidy, chimerism, and genome‐wide uniparental disomy are the cause of molar pregnancies, embryonic lethality, and developmental disorders. While triploidy and genome‐wide uniparental disomy can be ascribed to fertilization or meiotic errors, the mechanisms causing mixoploidy and chimerism remain shrouded in mystery. Different models have been proposed, but all remain hypothetical and controversial, are deduced from the developmental persistent genomic constitutions present in the sample studied and lack direct evidence. New single‐cell genomic methodologies, such as single‐cell genome‐wide haplotyping, provide an extended view of the constitution of normal and abnormal embryos and have further pinpointed the existence of mixoploidy in cleavage‐stage embryos. Based on those recent findings, we suggest that genome‐wide anomalies, which persist in fetuses and patients, can for a large majority be explained by a noncanonical first zygotic cleavage event, during which maternal and paternal genomes in a single zygote, segregate to different blastomeres. This process, termed heterogoneic division, provides an overarching theoretical basis for the different presentations of mixoploidy and chimerism.

中文翻译：

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胚胎全基因组异常：起源和临床后果

倍性或全基因组染色体异常，如三倍体、二倍体/三倍体混合倍体、嵌合体和全基因组单亲二体性是葡萄胎妊娠、胚胎致死率和发育障碍的原因。虽然三倍体和全基因组单亲二体可以归因于受精或减数分裂错误，但导致混合倍体和嵌合体的机制仍然笼罩在神秘之中。已经提出了不同的模型，但所有模型仍然是假设和有争议的，都是从研究样本中存在的发育持续基因组构成推导出来的，缺乏直接证据。新的单细胞基因组方法，如单细胞全基因组单体型分析，提供了正常和异常胚胎构成的扩展视图，并进一步确定了卵裂期胚胎中混合倍体的存在。基于最近的这些发现，我们认为在胎儿和患者中持续存在的全基因组异常在很大程度上可以通过非规范的第一次合子分裂事件来解释，在此期间，单个受精卵中的母本和父本基因组分离到不同的卵裂球。这个过程被称为异质分裂，为混合倍体和嵌合体的不同表现提供了总体理论基础。