A new genetic concept: Uniparental disomy and its potential effect, isodisomy

Abstract In recent years, cytogenetic studies of spontaneous abortion products have disclosed a relatively high frequency of aneuploid embryos. These karyotypic anomalies chiefly stem from meiotic errors affecting the distribution of the chromosomes in one of the two gametes. This information not only implies the remarkable frequency of gonocyte aneuploidy but also reveals the prevalence of certain types of errors. It follows that gametal haploidy is often altered by the loss (nullisomy) or the addition (disomy) of certain members, in particular the X, the Y, and chromosomes 15, 16, 21, and 22. Therefore, it is to be expected that, in some exceptional zygotes, euploidy could result from the random union of a disomic gamete with a gamete nullisomic for the homologue. To this hypothetical phenomenon ‐ which is, however, statistically likely and foreseeable ‐ we have ascribed the name of uniparental disomy, owing to the fact that both members of such a pair arise from only one parent. Furthermore, such a mechanism implies the probability of introducing into the genome pairs of chromosomes with whole sequences of identical alleles, a consequence which we describe by the neologism of isodisomy. Such homozygosity for a series of colinear alleles implies, from the genetic stand‐point, risks and advantages akin to those of parental consanguinity. An analogous mechanism could also modulate and modify the consequences of trisomies in which entire segments of two of the three implicated chromosomes, including the supernumerary one, could as well be isoallelic (isodisomic trisomy or di‐isotrisomy). This article briefly states some other predictions stemming from the concept of uniparental disomy, whose confirmation should serve as a test of the proposed hypothesis.