L. A. Livshits

Analysis of CCR5Δ32 Geographic Distribution and Its Correlation with Some Climatic and Geographic Factors

We studied the possible effects of climatic-geographic factors on the world distribution of the mutant allele for the chemokine receptor gene CCR5, which has a 32-bp deletion (CCR5Δ32) preventing cell invasion by the primary transmitting strain of HIV-1. New data on CCR5 polymorphisms in Russian, Ukrainian, and Moldavian populations are presented. All available data on CCR5Δ32 frequencies in the Old World (number of populations n = 77) were used for construction of a geographical gene map to analyze possible correlations between allele frequencies and eight climatic-geographic parameters. A strong positive correlation was found between the allele frequency and latitude (r = 0.72), a strong negative correlation with annual radiation balance (r = –0.66), and a weaker negative correlation with longitude (r = –0.34). Partial correlations were calculated excluding the influence of latitude. The negative correlation between the allele frequency and annual radiation balance decreased (r = –0.42), but remained large and significant. We propose that the existence of correlations between the cline of CCR5Δ32 frequencies and climatic-geographic parameters provides evidence for a possible effect of either natural environmental factors or large-scale population movements on the distribution of this allele.

Polymorphism of STR Loci of the Y Chromosome in Three Populations of Eastern Slavs from Belarus, Russia, and Ukraine

Allelic polymorphism of five microsatellite loci of the human Y chromosome (DYS19, DYS390, DYS391, DYS392, and DYS393) was analyzed in samples of male populations from Ukraine, Russia, and Belarus (152 subjects in total). The allelic diversity indices (Dg) were determined for all loci; they varied from 0.23 to 0.72. The mean values of this parameter in the Ukrainian, Russian, and Belarussian populations were 0.45, 0.47, and 0.52, respectively. A total of 53 different haplotypes were found in 152 subjects from three populations. The most frequent haplotype was found in 14.5% of the subjects, whereas 35 haplotypes (23%) were each found in only one person. The haplotypic diversity index (Dhp) was 0.94. The genetic distances between the populations studied and some populations of Western and Central Europe were estimated. These data were used to construct a phylogram (tree) of genetic similarity between the populations, which demonstrated that the three Eastern Slavic populations are genetically close to one another and remote from Western European populations.

Polymorphism of trinucleotide repeats in loci DM, DRPLA and SCA1 in East European populations

A normal polymorphism at three triplet repeat loci (myotonic dystrophy (DM), dentatorubral-pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 1 (SCA1)) were examined in healthy unrelated individuals from the Siberian Yakut (Mongoloid) population, the Adygei (Caucasian) population and nine East European populations: populations from Russia (Holmogory, Oshevensk, Kursk, Novgorod, Udmurts, Bashkir), two Ukrainian populations (Lviv and Alchevsk) and one Belarussian. The distribution of alleles for DRPLA and SCA1 were similar for all East-European populations. For the DM locus, East European populations had typical allele distribution profiles with two modes, (CTG)5 and (CTG)11–14, but some differences were found for the Bashkir population where alleles containing 11–14 CTG repeats had relatively higher frequency. The Yakut population had different allele spectra for all types of repeats studied. Higher heterozygosity levels and insignificant differences between expected and observed heterozygosity were found for all tested loci. The latter led us to suggest that the trinucleotide repeat loci analysed are not influenced by selection factors and could be useful for genetic relationship investigations in different populations.

TGFBI gene mutations in the Ukrainian patients with inherited corneal stromal dystrophies

Mutations Arg124Cys, Thr538Arg, Arg555Thr, Arg555Gln, Leu558Pro, and His626Arg in TGFBI gene were analyzed by polymerase chain reaction and restriction in 84 patients with various forms of corneal stromal dystrophies from 49 unrelated families and 29 clinically healthy relatives of these patients. A new mutation in TGFBI gene, Leu558Pro, was identified in the patients with atypical lattice dystrophy. The haplotypes of four microsatellite markers surrounding TGFBI gene region were analyzed in 22 families. The data on association of genotype and phenotype suggest that the analysis of TGFBI gene mutations is important for differential diagnostics of corneal dystrophies.

Association of PvuII polymorphism in ESR1 gene with impaired ovarian reserve in patients from Ukraine.

The association of ESR1 PvuII polymorphism (rs2334693) with impaired ovarian reserve was studied by genotyping this polymorphism using PCR-RFLP in patients and two control groups from Ukraine. Statistically significant differences in the prevalence of p-allele frequency (-397T) was seen in the group of patients with impaired ovarian reserve (0.597) compared to control groups I under 35years (0.480) and II over 35years (0.453), both p<0.05. The data suggest that PvuII polymorphism of ESR1 is associated with diminished ovarian reserve.

Allele frequencies for D1S80 (pMCT118) locus in some East European populations.

The Byelorussian populations are from three regions of the Republic of Belarus (Grodno, Bobruisk, and Mjadel areas); the Russians are from the Kholmogory town of the Russian Federation (Arkhangelsk district); and the Ukrainian populations are from the Kiev and L’vov areas of Ukraine. The Mordva-Moksha (StaroShaiginsk and Romodanovsk areas of Mordva Republic), the Bashkirs (Ilishevsky, Abzelilovsky, Sterlibashevsky, Arkhangelsky, and Beloretsky districts of Bashkir Republic), the Komi-Zyrjan (Sysolsky district of Komi Republic), the Tartar (Almetyevsk town of Tartar Republic), and the Mari (Zvenigovsk area of Mari Republic) populations present distinct ethnic groups of the region between the Volga River and the Ural Mountains in Russia. Eastern Slavonic populations (Russians, Byelorussians, Ukrainians) are Caucasoids; other populations were considered as admixture populations with different levels of a Mongoloid component. Blood samples were collected in EDTA vacutainer tubes from healthy unrelated volunteers belonging to a native ethnic group of the regions studied. DNA was isolated by phenol-chloroform ex

IL1β, IL6 and IL8 gene polymorphisms involvement in recurrent corneal erosion in patients with hereditary stromal corneal dystrophies

TGFBI gene mutations cause corneal stromal dystrophies of autosomal dominant inheritance. The most frequent complication of stromal dystrophies is recurrent corneal erosion with varying degree of accompanying inflammation. IL-1, IL-6 and IL-8 are main cytokines involved in corneal erosion healing. This study aimed to investigate the association between IL1B gene −511C/T, IL6 gene −174G/C and IL8 gene −781C/T polymorphisms and risk of recurrent erosion development in patients with hereditary corneal stromal dystrophies. A trend to decrease of IL1B gene −511TT genotype frequency in group with erosion (3.7%) comparing to control (6.7%) was observed. IL6 gene −174C allele carriers frequency in control group (65.9%) was significantly (P < 0.05) lower comparing to patients with erosion (80.5%). Frequency of IL8 −781TT genotype was significantly (P < 0.05) lower in the group with erosion (10.7%) comparing to patients without erosion (30.8%) and control (25%). IL6 gene −174C allele may be considered as genetic marker of corneal erosion risk in patients with hereditary stromal corneal dystrophies, whereas IL8 −781TT genotype is associated with negative recurrent erosion prognosis in such patients.

Analysis of allelic polymorphism in the ESR1 gene in the Ukraine’s population

In this study analysis of single nucleotide polymorhisms A351G, 397 and number of TA-repeats in ESR1 gene among 199 healthy volunteers from Ukraine was performed. Data concerning genotypes and particular alleles of polymorphic variants distribution were obtained. Possible mechanisms of these polymorphic variants role in ESR1 gene transcription and estrogen receptor expression changes are being discussed.

Molecular-genetics analysis of natural and stimulated ovulation impairment

The influence of FMR1, INHα1, NAT2, GSTT1 and GSTM1 genes mutations on ovarian function and their association with POF and “poor response” to exogenous GT after ovulation stimulation were investigated. The carriers of Ala257Thr transition predominated in the studied “poor responders” group. In 1.6% POF patients and 2.5% persons from “poor responders” group, but nobody from control group this transition combined with intermediate alleles of FMR1 gene was observed. The frequency of deletion in GSTM1 gene in “poor responders” group was significantly higher (p = 0.01) than in normal ovulatory control group. The frequency of Ser680Ser-Ala307Ala polymorphic genotype (22.2%) in “poor responders” group was significantly higher (p = 0.028) than in normal-ovulatory control group (7.7%). The daily dosage of GT in intermediate alleles of FMR1 gene carriers as well in patients with “slow acetylation” NAT2 genotype was significantly higher in comparison to patients without intermediate alleles and patients with “quick acetylation” NAT2 genotype. Quantity of oocytes after stimulation ovulation in women with INHα1 gene Ala257Thr transition were significantly decreased in comparison to patients without such mutation. Further investigations of these genes can play a major role in POF studying and modulation of ovarian response to exogenous GT.

Origin of dystrophin gene deletions in Duchenne and Becker muscular dystrophy patients from Ukraine

The results of the analysis of exon deletions and duplications in the dystrophin gene sequences from 121 Duchenne and Becker muscular dystrophy patients from Ukraine are presented. It is shown that the level of de novo deletions in these families reaches 53%, and most of the deletions are localized in the distal part of the gene. It is important to take into account these data in genetic counseling to assess the risk of birth of patients with DMD/BMD, including in prenatal diagnostics, in families with Duchenne and Becker muscular dystrophy patients.