Multilocus epimutations of imprintome in the pathology of human embryo development |
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Authors: | E A Sazhenova N A Skryabin N N Sukhanova I N Lebedev |
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Institution: | 1.Research Institute of Medical Genetics, Siberian Branch,Russian Academy of Medical Sciences,Tomsk,Russia |
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Abstract: | Genomic imprinting is one of the key epigenetic phenomena involved in embryonic development of eutherians and humans. Molecular
mechanisms of imprinting disturbances in the pathology of prenatal and postnatal onthogenesis are to a great extent related
to methylation abnormalities of the imprinted genes. Over recent years, data are accumulating on multiple abnormalities of
methylation simultaneously in several imprinted loci in the development of various pathologies that raises the issue of deciphering
the structural and functional organization of imprintome and the interaction of imprinted genes. The present work analyzes
DNA methylation of 51 imprinted genes in the placental tissues of human spontaneous abortions. We revealed multiple epimutations
in from four to 12 imprinted genes in every embryo. Most of the epimutations (78%) were of a postzygotic origin. It has been
established for the first time that the total incidence of methylation disturbance in maternal and paternal alleles of the
imprinted genes leading to embryo development suppression is significantly higher than the incidence of epimutations, which
stimulate embryogenesis. This fact supports at the epigenetic level the hypothesis of parent-offspring conflict that describes
the occurrence of a monoallelic expression of imprinted genes in mammalian evolution. |
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