Six isoforms of uncoupling proteins (UCPs) exist, spanning from UCP1 to UCP6. A precise physiological function has only been established for UCP1, which is involved in non-shivering thermogenesis, but the functions of other UCPs are still not fully defined. Therefore, the purpose of the present study is to search for indications of the involvement of nine polymorphic variants of UCP1-6 genes in human adaptation to cold climates using four criteria: (1) the presence of associations of polymorphic variants of UCP genes with levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine; (2) the presence of associations of polymorphic variants of UCP genes with changes in thyroid homeostasis (SPINA); (3) the presence of associations of polymorphic variants of UCP genes with body surface area; (4) the presence of signals of directional selection to cold climate for polymorphic variants of UCP genes. As a result of the evaluation, the highest scores for cold adaptation traits were recorded for polymorphic variants rs3811787 of the UCP1 gene and rs1800849 of the UCP3 gene. We suggest that the results obtained indicate the importance of uncoupling proteins UCP1 and UCP3 in human adaptation to cold through processes of non-shivering and shivering thermogenesis.

Previously only two families were known with progressive autosomal recessive deafness 103 (DFNB103, OMIM616042) caused by pathogenic variants of the CLIC5 gene. In this study we present the novel truncating variant c.644 G > A p.(Trp215*) of this gene which was found in homozygous state among 22 patients with hearing loss (HL) from 16 unrelated families living in the Sakha Republic of Russia (Eastern Siberia). Genotype-phenotype analysis in patients with DFNB103 showed that HL was sensorineural, symmetrical and variable by severity (from moderate to profound). Audiograms mostly have a down curve configuration, with pronounced loss of high and mid frequencies. In most cases this form of HL was detected in the post-lingual period (mean age 7.9 ± 1.2 years) and has a significant severity progression with age. In average the patients with DFNB103 lost 7.4 ± 13.65 dB on the speech frequency range in pure tone averages (PTA0.5,1.0,2.0,4.0 kHz) per year until reaching profound deafness in the second or third decade of the life. The high frequency of c.644 G > A p.(Trp215*) was found among Siberian GJB2-negative patients (9.9

It is currently accepted that the reproductive capabilities of deaf people increase over time, and marriages between deaf people occur according to the principle of assortativity, which in total can lead to an increase in the frequency of one major autosomal recessive form of deafness. In this regard, the purpose of this work was to analyze the share and structure of assortative marriages based on deafness in the Republic of Buryatia. The sample of deaf individuals consisted of 201 people (113 female and 88 male) aged from 21 to 77 years (mean age 46.7 ± 7.9 years). For analysis of the marriage structure of deaf people, information was available for 168 marriages. Individuals were considered married if they had a registered marriage and/or if they had common children. An assortative marriage (AM) was a marriage in which both partners were deaf. An AM in which all the children were deaf was considered non-complementary, and an AM in which all the children were hearing was considered complementary. Marriages in which there were both hearing and deaf children were designated as segregating. An analysis of the marriage structure of deaf people showed that the proportion of marriages between deaf individuals in Buryatia is 81.8% (122 out of 149 marriages analyzed), and in 18.2% of cases (27 marriages) marriages were concluded between deaf and hearing people. Among all AM, the share of complementary marriages was 86.9% (106 out of 122), non-complementary - 5.7% (7 out of 122) and segregating 7.3% (9 out of 122). It was revealed that with a high frequency of AM, the marital structure was characterized by a high proportion of complementary and low proportion of non-complementary and segregating AM, which may be explained by the peculiarities of the genetic structure of hereditary forms of hearing loss in the Republic of Buryatia. Keywords: hereditary hearing loss, assortative marriages, sign language, autosomal recessive deafness 1A (DFNB1A), Buryatia.

Mitochondrial forms account approximately 1–2% of all nonsyndromic cases of hearing loss (HL). One of the most common causative variants of mtDNA is the m.1555A > G variant of the MT-RNR1 gene (OMIM 561000). Currently the detection of the m.1555A > G variant of the MT-RNR1 gene is not included in all research protocols. In this study this variant was screened among 165 patients with HL from the Republic of Buryatia, located in the Baikal Lake region of Russia. In our study, the total contribution of the m.1555A > G variant to the etiology of HL was 12.7% (21/165), while the update global prevalence of this variant is 1.8% (863/47,328). The m.1555A > G variant was notably more prevalent in Buryat (20.2%) than in Russian patients (1.3%). Mitogenome analysis in 14 unrelated Buryat families carrying the m.1555A > G variant revealed a predominant lineage: in 13 families, a cluster affiliated with sub-haplogroup A5b (92.9%) was identified, while one family had the D5a2a1 lineage (7.1%). In a Russian family with the m.1555A > G variant the lineage affiliated with sub-haplogroup F1a1d was found. Considering that more than 90% of Buryat families with the m.1555A > G variant belong to the single maternal lineage cluster we conclude that high prevalence of this variant in patients with HL in the Baikal Lake region can be attributed to a founder effect.

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

The paper presents an analysis of the share and structure of assortative marriages (AM) based on deafness in the Republic of Buryatia. It was & Scy;& iecy;& vcy;& iecy;& rcy;& ocy;-& Vcy;& ocy;& scy;& tcy;& ocy;& chcy;& ncy;bIN cp & iecy;R & iecy;& rcy;& acy;n & softcy;& ncy;bIN & ucy;& ncy;Nrevealed that with a high frequency of AM, the marital structure was characterized by a high proportion of complementary and a low proportion of non-complementary and segregating AM, which is probably due to features of the genetic structure of hereditary forms of hearing loss in the Republic of Buryatia.

The basis of the research hypothesis is the assumption that in wooden structures, deformations and stresses propagate in waves. The numerical experiment demonstrated a correct qualitative visual picture of the wave propagation of deformations, with wave manifestations and characteristic effects on the surface of the sample, at axial and corner points. Visually, the numerical model showed Rayleigh waves on the surface layer of the sample, depending on the ratio of the external geometric dimensions of the sample model, with pronounced wave interference on the outer shell. The visual manifestation of deformation on the outer sides (faces) and the reflection of deformation waves from the outer boundaries of the elastic medium of the sample in the form of Rayleigh waves confirm the correctness of the general hypothesis and the implemented model. Visualization of the process of emergence, propagation and attenuation of deformation waves on the surface of the sample shows that in the quantitative description of the deformation gradient, areas dangerous for the material can be identified.

The audiological features of hearing loss (HL) in patients with autosomal recessive deafness type 1A (DFNB1A) caused by splice site variants of the GJB2 gene are less studied than those of patients with other variants of this gene. In this study, we present the audiological features of DFNB1A in a large cohort of 134 patients with the homozygous splice site variant c.-23+1G>A and 34 patients with other biallelic GJB2 genotypes (n = 168 patients with DFNB1A). We found that the preservation of hearing thresholds in the speech frequency range (PTA0.5,1.0,2.0,4.0 kHz) in patients with the c.[-23+1G>A];[-23+1G>A] genotype is significantly better than in patients with the “severe” c.[35delG];[35delG] genotype (p = 0.005) and significantly worse than in patients with the “mild” c.[109G>A];[109G>A] genotype (p = 0.041). This finding indicates a “medium” pathological effect of this splice site variant on hearing function. A detailed clinical and audiological analysis showed that in patients with the c.[-23+1G>A];[-23+1G>A] genotype, HL is characterized as congenital or early onset (57.5% onset before 12 months), sensorineural (97.8%), bilateral, symmetrical (82.8%), variable in severity (from mild to profound HL, median hearing threshold in PTA0.5,1.0,2.0,4.0 kHz is 86.73±21.98 dB), with an extremely “flat” audioprofile, and with a tendency toward slow progression (a positive correlation of hearing thresholds with age, r = 0.144, p = 0.041). In addition, we found that the hearing thresholds in PTA0.5,1.0,2.0,4.0 kHz were significantly better preserved in females (82.34 dB) than in males (90.62 dB) (p = 0.001). We can conclude that in patients with DFNB1A caused by the c.-23+1G>A variant, male sex is associated with deteriorating auditory function; in contrast, female sex is a protective factor.

In the world the role of pathogenic variants of the MYO15A gene in the etiology of hearing loss has not been sufficiently studied, since the large size of the gene (66 exons, 71 kb) suggests the search for pathogenic variants using NGS technologies, which are not yet sufficiently used in routine practice. In this regard, it is relevant to study the role of pathogenic variants of the MYO15A gene in the etiology of non-syndromic forms of hearing impairments. The purpose of this work is to describe the rare pathogenic variant c.7636C>T p.(Gln2546*) in the MYO15A gene, found in a homozygous state in two siblings with prelingual profound sensorineural hearing loss from a Buryat family. Previously, this variant was found only in one patient in a compound-heterozygous state with another nonsense variant in the MYO15A gene in Brazil and described as pathogenic. Detection of variant c.7636C>T p.(Gln2546*) in a homozygous state in Buryat siblings may indicate either a rare case of endogamous marriage or a wider distribution of this variant in the Lake Baikal region. Keywords: autosomal recessive deafness (DFNB3), MYO15A gene, variant c.7636C>T p.(Gln2546*), Republic of Buryatia.

Pathogenic variants of mitochondrial tRNA genes remain poorly understood in the context of the study of the etiology of hearing loss, despite the fact that they are one of the important causes of syndromic and non-syndromic hearing impairment as well as aminoglycoside-induced hearing loss. In this work, we searched for pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing impairments in Buryatia. One rare variant m.7445A>C was found in the MT-TS1 gene out of five investigated variants in one patient (1/165; 0.6%). This variant is localized in the coding region of two genes the MT-CO1 (H-chain) and MT-TS1 (L-chain), but on different mtDNA chains. However, a pathogenetic role for the m.7445A>C substitution has been shown for the MT-TS1 gene, but not for the MT-CO1 gene. In databases, the m.7445A>C variant is associated with nonsyndromic hearing loss, including those caused by aminoglycoside antibiotics. A comparative genotype-phenotypic analysis of our case and four cases with m.7445A>C of the MT-TS1 gene described earlier in the literature showed that hearing loss in all cases is not congenital, but at the same time varies in severity with low penetrance. The results obtained indicate the involvement of other modulating factors in the clinical manifestation of hearing impairment associated with this variant. Thus, further study of rare variants of MT-TS1 gene will contribute to our understanding of the pathogenetic mechanisms of mitochondrial forms of hearing loss.

The GJB2 (Cx26) gene pathogenic variants are associated with autosomal recessive deafness type 1A (DFNB1A, OMIM #220290). Direct sequencing of the GJB2 gene among 165 hearing-impaired individuals living in the Baikal Lake region of Russia identified 14 allelic variants: pathogenic/likely pathogenic-nine variants, benign-three variants, unclassified-one variant, and one novel variant. The contribution of the GJB2 gene variants to the etiology of hearing impairment (HI) in the total sample of patients was 15.8% (26 out of 165) and significantly differed in patients of different ethnicity (5.1% in Buryat patients and 28.9% in Russian patients). In patients with DFNB1A (n = 26), HIs were congenital/early onset (92.3%), symmetric (88.5%), sensorineural (100.0%), and variable in severity (moderate-11.6%, severe-26.9% or profound-61.5%). The reconstruction of the SNP haplotypes with three frequent GJB2 pathogenic variants (c.-23+1G>A, c.35delG or c.235delC), in comparison with previously published data, supports a major role of the founder effect in the expansion of the c.-23+1G>A and c.35delG variants around the world. Comparative analysis of the haplotypes with c.235delC revealed one major haplotype G A C T (97.5%) in Eastern Asians (Chinese, Japanese and Korean patients) and two haplotypes, G A C T (71.4%) and G A C C (28.6%), in Northern Asians (Altaians, Buryats and Mongols). The variable structure of the c.235delC-haplotypes in Northern Asians requires more studies to expand our knowledge about the origin of this pathogenic variant.

Митохондриальные формы потери слуха составляют не более 1–2% среди всех несиндромальных случаев тугоухости и глухоты. Одним из наиболее распространенных каузативных вариантов митохондриального генома является m.1555A>G гена MT-RNR1, который ассоциирован с формой глухоты, индуцируемой антибиотиками аминогликозидного ряда (OMIM:561000). В настоящее время вклад данной митохондриальной формы глухоты в этиологию потери слуха остается недостаточно изученным, поскольку детекция m.1555A>G гена MT-RNR1 входит не во все протоколы исследований. В настоящей работе методом ПЦР-ПДРФ анализа с последующим секвенированием по Сэнгеру впервые был проведен поиск патогенного варианта m.1555A>G гена MT-RNR1 у 165 пациентов с нарушениями слуха в Республике Бурятия. В результате, вариант m.1555A>G гена MT-RNR1 в состоянии гомоплазмии был обнаружен у 21 из 165 обследованных пациентов. Общий вклад m.1555A>G гена MT-RNR1 в этиологию нарушений слуха в Бурятии составил 12,7%, при этом высокая доля m.1555A>G гена MT-RNR1 выявлена у пациентов бурятов (20,2%) по сравнению с русскими пациентами (1,3%). Генетико-эпидемиологический анализ идентифицированной митохондриальной формы потери слуха в Бурятии выявил ее повышенную распространенность в трех районах на юге Республики, с максимальным накоплением в Джидинском муниципальном районе (4,5 на 10000). Анализ мировой распространенности варианта m.1555A>G гена MT-RNR1 среди 43435 пациентов с нарушением слуха показал, что его доля составляет в среднем 1,9%. Полученные результаты о высоком вкладе m.1555A>G гена MT-RNR1 в этиологию тугоухости и глухоты у пациентов бурятов свидетельствуют о том, что в регионе озера Байкал нами обнаружен один из наиболее крупных мировых очагов накопления митохондриальной формы потери слуха, который, вероятнее всего, обусловлен эффектом основателя. Mitochondrial forms of hearing loss account for no more than 1-2% among all non-syndromic cases of hearing loss. However, one of the most common causative variants of the mitochondrial genome is m.1555A>G of the MT-RNR1 gene, which is associated with a deafness induced by aminoglycoside antibiotics (OMIM:561000). Currently, the contribution of the mitochondrial deafness to the etiology of hearing loss remains insufficiently studied, since the detection of the m.1555A>G of the MT-RNR1 gene is not included in all research protocols. In this work, using PCR-RFLP analysis followed by Sanger sequencing, the pathogenic variant m.1555A>G of the MT-RNR1 gene for the first time was searched in 165 hearing impaired patients in the Republic of Buryatia. As a result, the m.1555A>G of the MT-RNR1 gene in the homoplasmic state was detected in 21 out of 165 studied patients. The total contribution of the m.1555A>G (MT-RNR1 gene) to the etiology of hearing impairment in Buryatia was 12.7%. At the same time, a high proportion of m.1555A>G of the MT-RNR1 gene was detected in Buryat patients (20.2%), compared to Russian patients (1.3%). A genetic-epidemiological analysis of the identified mitochondrial form of hearing loss revealed its increased prevalence in three south districts in the Republic of Buryatia, with the maximum accumulation in the Dzhidinskii district (4.5 per 10,000 peoples). The analysis of the global prevalence of the variant m.1555A>G of the MT-RNR1 gene among 43435 patients with hearing impairment showed that its share is on average 1.9%. The results obtained on the high contribution of the m.1555A>G to the etiology of hearing impairment in Buryat patients indicate that we have found in the Baikal Lake region one of the largest of the world accumulation of the mitochondrial forms of hearing loss with most likely due to founder effect.

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.

Патогенные варианты гена SLC26A4 ассоциированы как с аутосомно-рецессивной глухотой 4 типа (DFNB4, OMIM #600791), так и с синдромом Пендреда (PS, OMIM #274600). В настоящей работе проведен поиск каузативных вариантов гена SLC26A4 и анализ его генетического окружения (гаплотип CEVA) у шести пациентов из Бурятии с нарушениями слуха и расширенным водопроводом преддверия (EVA), которые в части случаев были сочетаны с кистозными аномалиями улитки (IP-1 и IP-2) и с нарушением тиреоидной функции. Исследование включало клинико-аудиологический анализ порогов слуха, компьютерную томографию височных костей, анализ гормонов гипофизарно-тиреоидной системы (ТТГ, св.Т3 и св.Т4), прямое секвенирование по Сэнгеру кодирующих районов гена SLC26A4 (21 экзон) и генотипирование 12 SNP-маркеров, составляющих гаплотип CEVA. В целом, у обследованных пациентов доля SLC26A4 биаллельных (M2) и моноаллельных случаев в сочетании с CEVA-гаплотипом в транс-положении (M1+CEVA) составила 83,3% (5 из 6 пациентов). При этом, у пациентов бурятов доля случаев с M2 составила 100% (3 из 3 пациентов), в то время как у русских пациентов доля случаев с М2 и М1+CEVA составила 66,6% (2 из 3 пациентов). Высокий мутационный вклад гена SLC26A4 у пациентов бурятов может быть связан с распространенностью в регионе озера Байкал мажорных вариантов этого гена c.919-2A>G (IVS7-2A>G) и c.2027T>A p.(Leu676Gln), характерных для ряда регионов Сибири и Восточной Азии. Идентификация гаплотипа CEVA в транс-положении у одного русского пациента с моноаллельным вариантом гена SLC26A4 (М1+CEVA), свидетельствует об актуальности дальнейшей оценки диагностической значимости CEVA-гаплотипа в когортах российских пациентов с нарушениями слуха. Pathogenic variants of the SLC26A4 gene are associated with both autosomal recessive deafness type 4 (DFNB4, OMIM #600791) and Pendred syndrome (PS, OMIM #274600). In this work, we searched for causative variants of the SLC26A4 gene and its genetic background (CEVA haplotype) in six patients in Buryatia with hearing impairments and an enlarged vestibular aqueduct (EVA), which in some cases was combined with cystic cochlear anomalies (IP-1 and IP-2) and with impaired thyroid function. The study included clinical and audiological analyses of hearing thresholds, computed tomography of the temporal bones, analysis of hormones of the hypothalamic– pituitary–thyroid axis (TSH, free T3 and free T4), direct Sanger sequencing of the coding regions of the SLC26A4 gene (21 exons) and genotyping of 12 SNPs markers of the CEVA haplotype. In general, among the studied patients, the proportion of SLC26A4 biallelic (M2) and monoallelic cases in combination with the CEVA haplotype in trans-position (M1+CEVA) was 83.3% (5 of 6 cases). At the same time, in Buryat patients, the proportion of cases with M2 was 100% (3 out of 3 cases), while in Russian patients, the proportion of cases with M2 and M1 + CEVA was 66.6% (2 out of 3 cases). The high contribution of the SLC26A4 gene in Buryat patients may be associated with the prevalence of the major variants of this gene c.919-2A>G (IVS7-2A>G) and c.2027T>A p.(Leu676Gln) common for regions of Siberia and Eastern Asia. Identification of the CEVA haplotype in trans-position in one Russian patient with a monoallelic variant of the SLC26A4 gene (M1+CEVA) indicates the relevance of further assessment of the diagnostic significance of the CEVA haplotype in cohorts of Russian patients with hearing impairments.

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.

An increase in the prevalence of autosomal recessive deafness 1A (DFNB1A) in populations of European descent was shown to be promoted by assortative marriages among deaf people. Assortative marriages became possible with the widespread introduction of sign language, resulting in increased genetic fitness of deaf individuals and, thereby, relaxing selection against deafness. However, the effect of this phenomenon was not previously studied in populations with different genetic structures. We developed an agent-based computer model for the analysis of the spread of DFNB1A. Using this model, we tested the impact of different intensities of selection pressure against deafness in an isolated human population over 400 years. Modeling of the "purifying" selection pressure on deafness ("No deaf mating" scenario) resulted in a decrease in the proportion of deaf individuals and the pathogenic allele frequency. Modeling of the "relaxed" selection ("Assortative mating" scenario) resulted in an increase in the proportion of deaf individuals in the first four generations, which then quickly plateaued with a subsequent decline and a decrease in the pathogenic allele frequency. The results of neutral selection pressure modeling ("Random mating" scenario) showed no significant changes in the proportion of deaf individuals or the pathogenic allele frequency after 400 years.

Thyroid hormones play a crucial role in regulating normal development, growth, and metabolic function. However, the controversy surrounding seasonal changes in free triiodothyronine (FT3) levels remains unresolved. Therefore, the aim of this study was to conduct a systematic review and meta-analysis of variations in FT3 levels in relation to seasonal air temperatures in the context of current knowledge about its role in nonshivering thermogenesis. Ten eligible articles with a total of 336,755 participants were included in the meta-analysis. The studies were categorized into two groups based on the air temperature: “Cold winter”, where the winter temperature fell below 0 °C, and “Warm winter”, where the winter temperature was above 0 °C. The analysis revealed that in cold regions, FT3 levels decreased in winter compared to summer (I2 = 57%, p < 0.001), whereas in warm regions, FT3 levels increased during winter (I2 = 28%, p < 0.001). These findings suggest that seasonal variations in FT3 levels are likely to be influenced by the winter temperature. Considering the important role of the FT3 in the nonshivering thermogenesis process, we assume that this observed pattern is probably related to the differences in use of thyroid hormones in the brown adipose tissue during adaptive thermogenesis, which may depend on intensity of cold exposure.

The article presents an overview of the role of assortative deafness marriages in the spread of hereditary hearing loss. In 1883, Alexander Graham Bell, the famous inventor of the telephone, first suggested that frequent marriages between deaf people could lead to an increase in the incidence of deafness, but this hypothesis was not recognized by his contemporaries. In the 2000s, with the development of molecular genetic studies, which made it possible to identify one of the most common forms of hearing loss due to gene mutations GJB2, connexin 26, which encodes the interstitial contact protein, has been reinterpreted by Walter Nance. In the series of studies, he and his coauthors were able to show that the reproductive capabilities of the deaf have increased, and marriages between the deaf occur not by chance, but by the principle of assortativity, which in total could lead to an increase in the prevalence of one of the most frequent "connexin" forms of hearing loss.

The main cause of congenital or juvenile cataract with autosomal recessive inheritance in Yakutia is the c.1621C>T p.(Gln541*) nonsense mutation in the exon 8 of the FYCO1 gene. Previous studies have shown that the c.1621C>T p.(Gln541*) mutation has spread to the territory of Yakutia as a result of the founder effect. The initial assessment of the average "age" of the mutation using the data of linkage disequilibrium for three STR markers: D3S3685, D3S3582 and D3S3561 showed a result of similar to 10.4 +/- 2.6 generations (260 +/- 65.0 years). In the present study, we used a different approach to determine the "age" of the c.1621C>T p.(Gln541*) mutation using the DMLE+ 2.3 software based on the analysis of 25 SNP markers. The calculated DMLE+ 2.3 "age" of the mutation, taking into account the 95% confidence interval, varies from 25 to 67 generations (from 625 to 1675 years). Comprehensive data show that the c.1621C>T p.(Gln541*) mutation could have occurred between the 4th and 18th centuries with the most likely time of expansion from 11th century.

Among the populations of Eastern Siberia, the Russian old-settlers of the village of Russkoe Ustye (Allaikhovsky district of Yakutia) occupy a special place: their origin is relations with people from the old possessions of Novgorod the Great (presumably around 1570). The investigation of the hypotheses of the origin of the people of Russkoe Ustye, are of considerable scientific interest for the study of the colonization process of Northern Eurasia. In this study analysis of the carrier frequency of the six mutations responsible for autosomal-recessive diseases in 30 unrelated individuals from the village of Russkoye Ustye was performed. In the population of the Russkoe Ustye we did not find any heterozygous mutations, which are the cause of phenylketonuria (0/30), Wilson disease (0/30), congenital cataract (0/30), progressive deafness (0/30), and methemoglobinemia (0/30). In this Siberian population with a carrier frequency of 6.7%, the c.35delG mutation of the GJB2 gene (2/30) responsible for autosomal recessive deafness 1 A was detected. The absence of local East-Siberian variants of founder mutations associated with congenital cataract, progressive deafness, and methemoglobinemia, which are prevalent among Turkic-speaking Yakuts, indicates that this Turkic component in population of Russkoe Ustye is absent or represented to a small extent. Increasingly, than the Turkic component in the in population of Russkoe Ustye is represented a common West-Eurasian component, as indicated by the presence of the c.35delG mutation of the GJB2 gene, which is common in Europe.