In this study, analysis of the mitochondrial gene pool structure of residents of the village of Russkoye Ust’ye was carried out. It was revealed that the spectrum of mitochondrial lines of the Russian old-settlers is represented by eight haplogroups and is characterized by the dominance of East Eurasian lineages C, D, G, F, and M13, which amounted to 66.7

There are different hypotheses on the origin and time of appearance of Russian settlements in the northeast of the Arctic. To study the history of the formation of northern old-settler population of Yakutia, Y-chromosome lineages were traced in representatives of the three groups of residents of the settlement of Russkoe Ust’ye, located in the delta of the Indigirka River (“Pomors,” “Cossacks” and “Zashivertsy”), comparable with the main migration waves of Russian arrival to the Arctic coast of Eastern Siberia. For the first time, the characteristic features of the genetic structure of Russkoustinian population are described based on the data of genome-wide analysis of 740 000 SNPs. The results of the study are more in favor of the “Pomor” hypothesis of the origin of Russkoustinians.

There are various hypotheses on the origin and time of the appearance of Russian settlements in the Arctic Ocean shores of Eastern Siberia. In order to study the history of the formation of the russian old-settlers of Yakutia, we analyzed the lineages of the Y-chromosome in three groups of residents of the village of Russkoye Ust’ye, located in the delta of the Indigirka River (“Pomors”, “Cossacks” and “Zashivertsy”), comparable with the main migration waves of settlement of Russians on the Arctic coast of Eastern Siberia. For the first time, the characteristic features of the genetic structure of the population of Russkoustinans are described by the data of a genome-wide analysis of 740,000 single nucleotide polymorphisms. The results of the study to a greater extent testify in favor of the “Pomor” hypothesis of the origin of the Russkoustinians.

The aim of this study is to conduct a comparative analysis of average irisin levels between female and male (with normal weight and obese) to assess sexual dimorphism. Circulating levels of irisin in the blood of 279 Yakuts (185 female, 94 male, average age 19.8 +/- 2.03 years) were determined. A comparative analysis of irisin levels between male and female in three BMI groups (underweight, normal weight, overweight/obesity) was carried out. The average level of irisin in the blood plasma in female was 8.33 +/- 2.74 mcg/mL, and in male 7.76 +/- 1.86 mcg/mL. Sexual dimorphism (p = 0.02) was detected in Yakuts with normal weight, where the level of irisin was higher in women (8.42 = 2.92 mcg/mL) compared to men (7.51 = 1.61 mcg/mL). Conducted a comparative analysis of irisin levels between male and female based on global data, were including this analysis are 2132 people. The age of the participants ranged from 18 to 61 years old. The meta-analysis was carried out for two different BMI groups: the first group included people with normal weight (18.5-24.9 kg/m(2)), the second group included people with varying degrees of obesity (>30 kg/m(2)). Comparative analysis of irisin levels in a large sample revealed statistically significant sexual dimorphism, where irisin levels were also higher in female compared to male, only in a sample of obese people (p = 0.02), in a sample of people with normal weight, no sexual differences were found (p = 0.09). Thus, the influence of obesity on sexual dimorphism was revealed.

The results of crack formation in a Cr–Zr surface alloy formed by a low-energy high-current electron beam are presented. The morphology and elemental composition of the surface alloy in the area of crack formation are investigated. It is shown that cracks propagate along the surface regardless of the location of pits and grooves, which indicates a greater dependence of cracking on the internal stresses rather than the roughness or other structural factors. It is found out that the distribution of elements affects the cracking of the surface alloy, which is indicated by its nearly equiatomic elemental composition in the area of crack formation.

ABSTRACTIt was evidenced, that the increase in the prevalence of autosomal recessive deafness 1A (DFNB1A) in populations of European descent was promoted by assortative marriages among deaf people. Assortative marriages become possible with a widespread introduction of sign language resulting in increased the genetic fitness of deaf individuals, thus relaxing selection against deafness. Currently, cochlear implantation is becoming a common method of rehabilitation for deaf patients, restoring their hearing ability and promoting the acquirement of spoken language. Whether the mass cochlear implantation could affect the spread of hereditary deafness is unknown. We have developed an agent-based computer model for analysis of the spread of DFNB1A. Using the model, we tested impact of different intensity of selection pressure on an isolated human population for 400 years. The modeling of the “purifying” selection pressure on deafness resulted in decrease of the proportion of deaf individuals and the pathogenic allele frequency. The modeling of relaxed selection resulted in increase of the proportion of deaf individuals and the decrease of the pathogenic allele frequency. The results of neutral selection pressure modeling showed no significant changes in both the proportion of deaf individuals and the pathogenic allele frequency after 400 years. Thus, initially low genetic fitness of deaf people can be significantly increased in the presence of assortative mating by deafness, resulting in a higher prevalence of DFNB1A. Contrary, frequency of pathogenic allele and the incidence of hereditary hearing loss will not increase in a population where all deaf individuals undergo cochlear implantation.

We present the results of analysis of skin epidermis thickness in individuals with recessive mutation c.-23+1G>A in the GJB2 gene in comparison with individuals without this mutation living in Eastern Siberia (Yakut population). We examined 152 individuals with different genotypes by GJB2 gene mutation c.-23+1G>A . Homozygotes and heterozygotes by c.-23+1G>A have thicker epidermal layer (0.245 mm and 0.269 mm, respectively) in comparison with individuals without this mutation (0.193 mm) ( p <0.05). The obtained data support the hypothesis about selective advantage of carriers of mutant GJB2 gene alleles and partly explain extremely high carrier frequency (10.3%) of c.-23+1G>A mutation in the GJB2 gene in Yakut population in Eastern Siberia.

Reconstruction of the mitochondrial genome of a horse from the Ashna-Pando hillfort (the Sura River basin, Middle Volga, Ulyanovsk oblast, Russia) was performed using bone remains. It was established that, according to a fragment of the control region (D-loop), the specimen belongs to the B1 haplotype widespread among modern as well as ancient horses of Europe and Asia. However, in accordance with complete mitochondrial genome analysis, the horse is attributed to the M haplogroup that includes different modern breeds, with the Akhal-Teke breed among them. The obtained data make it possible to postulate the steppe origin of the horse. On the basis of our analysis, penetration of the southern horses deep into the broadleaf forest area likely dates to the second or third quarter of thefirst millennium BC and is probably connected with interactions of the sedentary population of the Sura River region with Scythian nomads.

Autosomal recessive deafness type 1A (DFNB1A) caused by mutations in the GJB2 gene (Cx26) is the main cause of nonsyndromic hearing impairment in many populations worldwide. It is considered that widespread prevalence of DFNB1A can be due to the long tradition of intermarriages between deaf people (assortative marriages) combined with their increased social adaptation and genetic fitness after widespread introduction of sign language. For the first time, the data on mating structure and reproduction of deaf people living in Yakutia (Eastern Siberia, Russia) are presented in comparison with contribution of the GJB2 gene mutations to the etiology of hearing impairment. The relative fertility of deaf people compared to their hearing siblings is 0.78 (mean number of children 1.76 ± 0.10 and 2.24 ± 0.09 to deaf and their hearing siblings, respectively, p = 0.0018). The rate of assortative marriages among deaf people is 77.1% (81 of 105 marriages). Biallelic mutations in the GJB2 gene were found in 42.2% (43 of 102) of examined deaf people, which corresponded to diagnosis DFNB1A for these patients. A comparison of deaf marital partners by GJB2 status revealed a proportion of noncomplementary marriages (24%) in which hearing loss in both partners was caused by the presence of biallelic GJB2 gene mutations resulting in the birth of only deaf children in such couples. Thus, the set of obtained data including a relatively high genetic fitness (expressed as relative fertility) of deaf people in Yakutia in combination with a high rate of assortative marriages among them and high incidence of DFNB1A indicates a possible weakening of selection against such trait as “deafness” and a possible increase in the frequency of GJB2 mutant alleles in subsequent generations.

In this paper we present for the first time the results of the audiological and clinical-genealogical research of the population of settlements Batagai-Alyta and Kustur of the Eveno-Bytantaisky National District (ulus) of the Sakha Republic (Yakutia) for studying the postlingual form of deafness of unknown etiology firstly identified by us earlier in 3 Evens. As a result of an audiological examination of 72 people, 10 patients from 6 nuclear families who met the criteria of postlingual form of hearing loss were found. The segregation analysis carried out in these families confirmed the autosomal recessive type of inheritance of this form of postlingual hearing loss. The distant relationship of the examined patients with postlingual hearing loss living in two villages of the Eveno-Bytantaisky National District of the Sakha Republic can indicate to the role of the founder effect in the local prevalence of this pathology.

We conducted a questionnaire and a selection of buccal epithelium of people, whose mean age is 21, in order to analyze their opinion on the potential risk of a deaf child's birth and conduct genetic testing for the presence of the mutation c.-23+1G>A in the GJB2 gene. Analysis of data from the questionnaire with genotypes shows that there are no statistically significant differences in the respondents' responses (p>0.05). As a result of the questionnaire, it is shown that most young hearing people think that deafness can be a hereditary disease. Most young people assume the possibility of birth of a deaf child from hearing parents, but very few respondents agree with this risk. Such a response can be explained by the protective internals of the psyche, when a person assumes the existence of the same risk of the birth of a deaf child in all people. In heterozygous carriers of the mutation c.-23+1G>A in the gene GJB2, there is a tendency to assume the hereditary nature of deafness more often than in people without this mutation.Such a response can be explained by the presence of close deaf/hard-of-hearing relatives.

The high carrier frequency of c.-23+1G>A mutation in the GJB2 gene in Yakut population is might be explained not only by the factors of population dynamics (founder effect, genetic drift, small effective population size), but also can be due to the selective advantage of heterozygous mutations in the GJB2 gene. Because the GJB2 gene is expressed not only in the cochlea but also in other tissues, and in vitro studies conducted on cell cultures show that GJB2-mutant cells were more resistant to the infection of dysentery - Shigella flexneri. The aim of this study is the analysis of the resistance in heterozygous carriers of the c.-23+1G>A mutation in GJB2 gene to diarrhea. Material and methods. We examined 272 Yakut individuals, which was divided into two groups: the first group consisted from 238 individuals without c.-23+1G>A mutation, the second group consisted from 34 individuals with c.-23+1G>A mutation in heterozygous state. All respondents independently filled information about the number of cases of diarrhea in the last year, and indicated the most characteristic form of their stool. Results and Discussion. In heterozygous carriers of the c.-23+1G>A mutation the cases of diarrhea in the last year were not registered in 22% of individuals, in individuals without mutation cases of diarrhea were not registered in 5% of individuals. According to the results of this study heterozygous carriers of the c.-23+1G>A mutation statistically significantly are less susceptible to diarrhea cases than individuals without this mutation. Thus, the obtained results can support the hypothesis about selective advantage of the GJB2 gene mutant alleles carriers and partly explain the extremely high carrier frequency (10.3%) of the c.-23+1G>A mutation in the GJB2 gene in Yakut population.

The c.-23+1G>A splice site mutation is one of the most frequent mutations of gene GJB2 (Cx26, 13q11-q12) associated with congenital non-syndromic autosomal recessive deafness. This mutation is characterized by a wide spread from Eastern Siberia and Central Asia to Eastern Europe, the Middle East, and South Asia. It is currently unknown whether this mutation spread over such a vast territory as a result of the founder effect or there were several local centers of origin of this mutation. For the first time, on the basis of the analysis of variability of nine SNP markers, five different haplotypes in deaf patients homozygous for mutation c.-23+1G>A from six Eurasian populations were reconstructed. The structure of the haplotypes revealed in Yakuts, Russians, Evenks, Tuvinians, Mongols, and Turks makes it possible to assume that mutation c.-23+1G>A (GJB2) could have spread across Eurasia as a result of the founder effect. The greatest diversity of haplotypes with c.-23+1G>A was found in patients from Mongolia, which probably refers to the earlier period of expansion of haplotypes carrying this mutation on the territory of Central Asia.

Тhe DNA testing of autosomal recessive deafness type 1A (DFNB1A, MIM 220290) is complicated when deaf patients have only monoallelic (heterozygous) recessive mutations in the GJB2 (Сх26) gene that is uninformative for establishment of diagnosis. Such patients may be “random” heterozygous carriers of GJB2 mutations as well as have the mutant allele in a cis-regulatory region of GJB2 gene, in element genes encoding other connexins: GJB6 (Сх30) or GJB3 (Сх31). Previous studies of genetic causes of hearing loss in patients from Yakutia were directed to search for only mutations in the GJB2 gene, and the DNA diagnostics was uninformative for 9.7% (38/393) of the patients with monoallelic GJB2 mutations. In this work the search for mutations in genes GJB3 and GJB6 and two deletions с.del(GJB6-D13S1830) and с.del(GJB6-D13S1854) to the cis-regulatory region of GJB2 gene was conducted in 35 patients with GJB2 monoallelic mutations and in 104 normal hearing individuals. The genes studied are two synonymous substitution c.489G>A (р.Leu163Leu) (GJB6) and c.357C>T (р.Asn119Asn) (GJB3) have been found, probably do not have clinical significance, and two nonsynonymous substitution c.301G>A (p.Glu101Lys) (GJB6) and с.580G>A (p.Ala194Thr) (GJB3). Additional experimental evidences are needed for confirmation of pathogenic significance of detected nonsynonymous substitutions in development of hearing loss in studied patients. Diagnosis of the DFNB1A was confirmed in only one patient, who was discovered by the deletion с.del(GJB6-D13S1830) (GJB2) in combination with a recessive mutation с.35delG (GJB2). In general, our results indicate low contribution of mutations in genes GJB6 and GJB3 in hearing loss etiology in Yakutia.