Sadovnychenko I. Genetic study of ichthyosis in Kharkiv region

The thesis presents molecular genetic/cytogenetic features of X-linked recessive ichthyosis and ichthyosis vulgaris, frequency of alleles and genotypes of folate metabolism-related genes, parameters of linkage disequilibrium, prevalence of single-gene and chromosomal disorders, the fixation index FST, values of mean age at marriage, mean distance and intensity of migration, marital distance in Kharkiv region, the analysis of correlation between the prevalence of genetic disorders and other population genetic parameters. In patients with X-linked recessive ichthyosis and their relatives, an interstitial deletion of the STS gene ish del (Х)(p22.31p22.31)(STS–) was detected. Geographical features of distribution of alleles and genotypes of FLG gene and polymorphisms in folate metabolism-related genes in European countries were established. The highest risk of ichthyosis development among heterozygotes for FLG 2282del4 mutation was found in individuals with the genotype MTHFR 677CT/MTR 2798AA/MTR 2756AA/MTRR 66AG (OR = 11.2; 95% CI 2.512–50.209; p = 0.002). In patients with ichthyosis, two LD blocks were detected. The first one included SNPs of the MTHFR gene (C677T and A1298C), that demonstrated strong linkage (D' = 1.00; LOD = 2.32; r2 = 0,195). The second block consisted of mutations in the FLG gene (2282del4 and R501X) with incomplete linkage (D' = 1.00; LOD = 1.53; r2 = 0.109). A positive correlation was found between the rates of fixation index FST and the prevalence of chromosome abnormalities (r = 0.904).