Evaluation of the Role of Uniparental Disomy in Early Embryolethality of Man

摘要

We carried out systematic studies oi the contribution of uniparental disomy for eight human chromosomes, 2, 9, 11, 15, 16, 19,20, and 21, to the etiology of embiyolethality Most of these chromosomes have regions with orthologous imprinted genes syntenic with those on mouse chromosomes, the disturbed expression of which is related to embryolethality in mice Screening of uniparental disomy in spontaneous abortuses of 5-16 weeks of pregnancy was performed by evaluation of the pattern of inheritance of alleles of polymorphic mic-rosatellite loci located in the studied chromosomes. A total of 100 human embryos with cytogenetically determined normal karyotype were studied, in which arrest at the early stages of intrauterine development was determined by ultrasound examination of pregnant women. During this study, 13 embryos were discarded due to revealed karyotype anomalies or nonpaternity. No cases of uniparental disomy were found among the 87 studied abortuses for any of chromosomes studied. The analysis of the results of this study and four other studies concerning the search for uniparental disomy in dead embryos and fetuses did not reveal its elevated frequency in spontaneous abortuses as compared to the theoretically expected value based on evaluation of the probable combination of meiotic errors in human gametes The data we obtained suggest that, first, uniparental disomies for human chromosomes that have regions with orthologous imprinted genes syntenic with mouse chromosomes do not contributenoticeably to the death of human embryos at the early developmental stages and, second, the mechanisms underlying embryolethality as a result of disturbed expression of imprinted loci differ markedly in evolutionarily remote mammals.