Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Hum Mol Genet. 2010 Apr 1;19(7):1263-75. doi: 10.1093/hmg/ddq003. Epub 2010 Jan 6.
Mosaic aneuploidy and uniparental disomy (UPD) arise from mitotic or meiotic events. There are differences between these mechanisms in terms of (i) impact on embryonic development; (ii) co-occurrence of mosaic trisomy and UPD and (iii) potential recurrence risks. We used a genome-wide single nucleotide polymorphism (SNP) array to study patients with chromosome aneuploidy mosaicism, UPD and one individual with XX/XY chimerism to gain insight into the developmental mechanism and timing of these events. Sixteen cases of mosaic aneuploidy originated mitotically, and these included four rare trisomies and all of the monosomies, consistent with the influence of selective factors. Five trisomies arose meiotically, and three of the five had UPD in the disomic cells, confirming increased risk for UPD in the case of meiotic non-disjunction. Evidence for the meiotic origin of aneuploidy and UPD was seen in the patterns of recombination visible during analysis with 1-3 crossovers per chromosome. The mechanisms of formation of the UPD included trisomy rescue, with and without concomitant trisomy, monosomy rescue, and mitotic formation of a mosaic segmental UPD. UPD was also identified in an XX/XY chimeric individual, with one cell line having complete maternal UPD consistent with a parthenogenetic origin. Utilization of SNP arrays allows simultaneous evaluation of genomic alterations and insights into aneuploidy and UPD mechanisms. Differentiation of mitotic and meiotic origins for aneuploidy and UPD supports existence of selective factors against full trisomy of some chromosomes in the early embryo and provides data for estimation of recurrence and disease mechanisms.
嵌合体非整倍体和单亲二倍体（UPD）是由有丝分裂或减数分裂事件引起的。这些机制在以下方面存在差异：（i）对胚胎发育的影响；（ii）嵌合体三体和 UPD 的同时发生；（iii）潜在的复发风险。我们使用全基因组单核苷酸多态性（SNP）阵列研究了染色体非整倍体嵌合体、UPD 患者和一个 XX/XY 嵌合体个体，以深入了解这些事件的发育机制和时间。16 例嵌合体非整倍体源于有丝分裂，其中包括四种罕见的三体和所有的单体，这与选择因素的影响一致。五例三体发生在减数分裂中，其中三例在二倍体细胞中有 UPD，证实了减数分裂非分离情况下 UPD 的风险增加。通过分析每条染色体可见的 1-3 个交叉，可看到非整倍体和 UPD 的减数分裂起源的证据。UPD 的形成机制包括三体挽救，伴有或不伴有同时的三体，单体挽救，以及有丝分裂形成嵌合体片段性 UPD。在一个 XX/XY 嵌合体个体中也发现了 UPD，其中一个细胞系具有完整的母体 UPD，与单亲生殖起源一致。SNP 阵列的利用允许同时评估基因组改变，并深入了解非整倍体和 UPD 机制。区分有丝分裂和减数分裂起源的非整倍体和 UPD 支持在早期胚胎中存在针对某些染色体完全三体的选择因素，并为估计复发和疾病机制提供数据。
