[Angelman syndrome--the research model of epigenetic mechanisms expression genes regulation]

Epigenetics, one of the widely investigated topics in human genetics, refers to phenotypic or gene expression changes caused by specific regulatory mechanisms (eg. DNA methylation, histone proteins modifications, antisense RNA or RNAi expression) that do not involve changes in DNA sequence. The disturbances in epigenetic gene expression regulatory mechanisms might lead to oncogenic transformation as well as monogenic or complex diseases. On the other side, better knowledge about epigenetic causes of certain diseases, gives an opportunity to potential therapies. One of the epigenetic research models in Angelman syndrome (AS). This neurologic disorder associated with improper central nervous system development and function, together with Prader-Willi syndrome are caused by the defects of epigenetic regulation. These disturbances are related to the defects of genomic imprinting, a phenomenon that contributes to allele specific, depending from parental origin, gene expression. In the majority of AS cases, the large deletion in chromosome 15 (15q11-13) of maternal origin (65-75%) or paternal disomy of chromosome 15 (3-7%) are observed. However, in a limited number of cases, other imprinting defects or mosaicism can be found and confirmed by new molecular biology techniques. Investigation of the etiology of the diseases caused by the defects in epigenetic regulation gives a basis to the development of epi-therapy that might be a promising alternative for their treatment. Moreover, knowledge about the epigenome gives an opportunity for prevention of human genetic disorders.