Euploid Chromosome Aberrations, Uniparental Disomy, and Genomic Imprinting

Abstract

In some individuals, both copies of a particular chromosome come from one parent and none from the other, this is called uniparental disomy (UPD) (Engel, 1980). It is not yet clear how common each type of uniparental disomy is, but many deviations from Mendelian inheritance could be explained by it, as described below. Most UPD has a meiotic origin that leads to a trisomie zygote, with loss of one copy of the chromosome in a subsequent mitosis. One-third of the time, the single copy from one parent will be lost, producing UPD. Trisomy of meiotic origin is usually the result of maternal meiosis I nondisjunction, so most UPD of meiotic origin is maternal UPD (Robinson et al., 1997). Paternal UPD is more likely to have a postzygotic origin from a normal zygote by mitotic nondisjunction. A much smaller proportion of maternal UPD arises in this way. Trisomie cells produced by mitotic nondisjunction have two identical copies of the chromosome from one parent. In trisomies due to meiotic nondisjunction, restoration of disomy by loss of a chromosome will produce uniparental isodisomy one-third of the time. The two identical chromosomes are, naturally, homozygous at all their gene loci, including any that are mutated. UPD of a maternally derived chromosome has been observed for chromosomes 1, 2, 4, 6, 7, 9, 10, 13–16, 21, 22, and X. Paternal UPD has been observed for chromosomes 1, 5–8, 11,13–16, 20–22, X, and XY (Engel, 1998). For years, the most commonly observed UPDs were those of chromosomes 7, 11, 14, and 15, perhaps because these are associated with characteristic phenotypes that bring them to medical attention and cytogenetic study.