A global disorder of imprinting in the human female germ line

• Published in: Nature (London) Vol. 416; no. 6880; pp. 539 - 542
• Main Authors: Bonthron, David T, Judson, Hannah, Hayward, Bruce E, Sheridan, Eamonn
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 04.04.2002; Nature Publishing Group
• Subjects: Adult; Biological and medical sciences; Consanguinity; Defects; DNA Methylation; Female; Fundamental and applied biological sciences. Psychology; Gene therapy; Genes; Genetic Markers; Genomic Imprinting; Human genome; Humans; Hydatidiform Mole - genetics; Male; Molecular and cellular biology; Mutation; Oocytes; Ovarian Neoplasms - genetics; Polymerase Chain Reaction; Pregnancy; Properties; Sulfites; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/416539a

Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment.