Makukh H. The mutations inherited as a genetic load: frequency, phenotype associations, diagnosis.

The thesis presents a theoretical synthesis and a new solution of problem of segregated part of the genetic load studies by establishing the distribution and characteristics of the spectrum of mutations that are phenotyply manifested at different stages of ontogenesis in the form of human diseases and on the basis of the obtained data suggests the ways to improve the efficiency of genetic testing. It has been found that CFTR gene mutation 2184insA (7.5% of mutant alleles) is the second most frequent allele among Cystic Fibrosis patients from Ukraine. A new CFTR gene mutation - c.1086T> A (p.Tyr362X) has been discovered and described for the first time. It has been proved that AZFc partial deletions are not only a polymorphism variant but a genetic factor of men spermatogenesis disorders. It has been described the relationship between Y-chromosome haplotypes and AZFc region partial deletions: haplogroup N increases the risk of b2/b3 partial deletion, and the haplotype R1a1 increases the risk of gr/gr partial deletion. The data on the distribution of alleles and genotypes of MTHFR, MTR, MTRR, FV, FII, PAI-1, IGF2, HFE, CFTR, SMN, PAH, NBN AZF genes and Y-chromosome haplotypes among the inhabitants of the Western region of Ukraine have been obtained as a result of the research.