Epimutations in Human Disease
- 1.2k Downloads
Epigenetics is the study of genes during development. Gene expression states are set by transcriptional activators and repressors and locked in by cell-heritable chromatin states. Inappropriate expression or repression of genes can change developmental trajectories and result in disease. Aberrant chromatin states leading to aberrant gene expression patterns (epimutations) have been detected in several recognizable syndromes as well as in cancer. They can occur secondary to a DNA mutation in a cis- or trans-acting factor, or as a “true” or primary epimutation in the absence of any DNA sequence change. Primary epimutations often occur after fertilization and lead to somatic mosaicism. It has been estimated that the rate of primary epimutations is one or two orders of magnitude greater than somatic DNA mutation. Therefore, the contribution of epimutations to human disease is probably underestimated.
KeywordsAngelman Syndrome Epigenetic State Assisted Reproduction Technology Somatic Mosaicism Neonatal Diabetes Mellitus
Unable to display preview. Download preview PDF.
- Gillessen-Kaesbach G, Demuth S, Thiele H, Theile U, Lich C, Horsthemke B (1999) A previously unrecognised phenotype characterised by obesity, muscular hypotonia, and ability to speak in patients with Angelman syndrome caused by an imprinting defect. Eur J Hum Genet 7:638–644PubMedCrossRefGoogle Scholar
- Prawitt D, Enklaar T, Gaertner-Rupprecht B, Spangenberg C, Oswald M, Lausch E, Schmidtke P, Reutzel D, Fees S, Lucito R, Korzon M, Brozek I, Limon J, Housman D, Pelletier J, Zabel B (2005) Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms’ tumor. Proc Natl Acad Sci USA 102:4085–4090PubMedCrossRefGoogle Scholar
- Ying AK, Hassanain HH, Roos CM, Smiraglia DJ, Issa JJ, Michler RE, Caligiuri M, Plass C, Goldschmidt-Clermont PJ (2000) Methylation of the estrogen receptoralpha gene promoter is selectively increased in proliferating human aortic smooth muscle cells. Cardiovasc Res 46:172–179PubMedCrossRefGoogle Scholar
- Zogel C, Böhringer S, Groß S, Varon R, Buiting K, Horsthemke B (2006) Identification of cis-and trans-acting factors possibly modifying the risk of epimutations on chromosome 15. Eur J Hum Genet (in press)Google Scholar