Hryshchenko N. Genome Rearrangements in Patients with Dominant Neurodegenerative Diseases (Hereditary Polyneuropathies and Huntington's Disease)

Object - inherited autosomal dominant neurodegenerative diseases (hereditary polyneuropathies and Huntington's disease). Goal is to study the nature and origin of genome rearrangements in 17р11.2 region, Сх32 and ІТ15 genes, and also the mutation's association with clinical phenotype of hereditary polyneuropathies and Huntington's disease. Methods - genealogical, laboratory molecular biological: isolation and purification of genomic DNA, polymerase chain reaction (qualitative PCR and quantitative Real-Time PCR), restriction analysis, different types of electrophoresis including PCR-fragments' analysis by ALF-express fluorometer and denaturing gradient gel electrophoresis (DGGE), DNA sequencing, and also statistical analysis. Results and their novelty - the high frequencies of 17р11.2-rearrangements in patients with hereditary polyneuropathies in Ukraine and also high level of the rearrangements de novo have been obtained. The 65G>A mutation in Cx32 gene (Arg22Gln in protein), which leads to demyelinating form of polyneuropathy, has been identified. The recurrent origin of expanded CAG-alleles of ІТ15 gene in Ukrainian patients with Huntington's disease has been proved. The sex-depended pattern of dynamic IT15 CAG-expansions inheritance has been revealed. A negative correlation has been defined between Huntington disease's age of onset and number of CAG-repeats in expanded IT15 allele, presence of del2642 mutation of IT15 gene and also presence of С677Т mutation of MTHFR gene. The field is molecular genetics.