Functional relevance of epigenetics in mental retardation.

Mental retardation (MR) is a disease of the brain which significantly decreases intellectual ability. In more than 50% of the MR patients for which a genetic factor has been proposed, the causal mutation in the DNA sequence remains unknown. There is however, growing evidence for a link between epigenetics and the development of the nervous system. Epigenetics is often described as the make up‟ of DNA since it can result in heritable changes in DNA-dependent processes without changing the DNA sequence itself. For this reason, we aim to look for changes in this epigenetic make up‟ in MR patients when compared to control individuals. The best known epigenetic players are modifications of the histone proteins that are tightly associated with DNA, and methylation of DNA; this project will focus on histone modifications on the X chromosome since we have access to several unsolved MR families with a clear X-linked inheritance pattern. Additionally, we also aim to characterize two new candidate MR genes for their role in chromatin-related processes. Some known MR genes were recently proven to play a role in chromatin-related processes based upon the presence of specific protein domains. Our candidate MR genes also have these specific protein domains.

Keywords:Mental retardation, X-linked mental retardation, Epigenetics, Histone modification, Chromatin, DNA methylation

Disciplines:Genetics, Systems biology, Molecular and cell biology