Розробка підходів для характеристики сегрегаційної складової генетичного тягаря у людини

Abstract

Aims. Evolutionary accumulated mutant alleles that cause human diseases are segregated part of the genetic load in human. One approach to estimate the segregation part of the genetic load in humans is not existed. The objectives of the study – to develop and propose the approaches for segregation component of genetic load characterizing. Methods. 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 composed and examined. Results. The segregated part of the genetic load was defined 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. It has been found that CFTR gene mutation 2184insA is the second most frequent allele among Cystic Fibrosis patients from Ukraine. 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. Conclusions. It has been developed and applied the diagnostic approach that includes an analysis of maternal and fetal genotype in case of spontaneous abortions, the study of the frequency of heterozygous carriers of the most common autosomal recessive diseases and the analysis of genetic factors of impaired spermatogenesis in men.

Key words: genetic load, mutation, human diseases, genetic testing.