[Multilocus epimutations of imprintome in the pathology of embryo development].
Genomic imprinting is one of the most significant epigenetic phenomena, which is involved in the support of eutherians and human embryo development. Molecular mechanisms of imprinting disturbance in the pathology of pre- and postnatal ontogeny are related to a considerable degree to aberrant DNA methylation of imprinted genes. At present time data about multiple abnormalities of DNA methylation arising simultaneously in several imprinted loci are accumulated. This fact brings up the problem of interpretation of imprintome structural and functional organization, as well as interaction of imprinted genes. At present study DNA methylation analysis of 51 imprinted genes in placental tissues of human spontaneous abortions was performed. The presence of several epimutations affected from four to 12 imprinted genes was observed in each embryo. Majority of epimutations (78%) had a postzygotic origin. It was shown for the first time that the total incidence of abnormal DNA methylation of maternal and paternal alleles of imprinted genes, which lead to suppression of embryo development, is significantly higher than the incidence of epimutations, which can lead to stimulation of ontogenesis processes. This fact supports at the epigenetic level the "sex conflict" hypothesis, which explains the appearance of monoallelic imprinted genes expression in the evolution of mammals.
E A
EA
Sazhenova
N A
NA
Skriabin
N N
NN
Sukhanova
I N
IN
Lebedev
D000022:Abortion, Spontaneous / Q000235:genetics / Q000473:pathology; D000328:Adult; D019175:DNA Methylation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D056426:Genetic Loci; D018392:Genomic Imprinting; D006801:Humans; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy