The study of genetic history through Y-chromosome polymorphism in modern and ancient populations helps reconstruct ethnogenesis. Research on the Nogai gene pool, as descendants of ancient nomads, allows tracing migration routs in the Eurasian steppe corridor. The Nogai ethnic group formed in the Middle Ages, as a result of interactions of the populations of the Central Asian, West Siberian, Ural-Volga, North Caucasian, and East European historical and cultural regions. A unified expanded panel of Y-chromosome haplogroups was used to study four main populations of the Nogai people: Astrakhan, Kuban, Stavropol, and Karanonogais. The total sample (N=368) revealed a diverse spectrum of 32 Y-haplogroups, with no single haplogroup dominating in any of these groups. Astrakhan Nogais show high frequencies of C-M217 and J-M172, while Kuban Nogais have an exceptionally high frequency of R-M198 and its “European” subclade R-M458. Karanogais display a distinct combination of R-M198(xM458), N-M178, R-Y13887, and J-M172(xM67, M12). Stavropol Nogais combine R-M198(xM458) and C-M217. The Nogai gene pool is characterized by the accumulation of “steppe” Y-chromosome variants, which is obviously related to the tribes of the steppe belt of Eurasia, probably of pre-Turkic origin. Increased J-M172 frequency may result from ancient Neolithic migrations along the Caspian coast and later nomadic movements. “Steppe” variants of the Nogai Y-chromosome popu­lation were also identified in samples from burials at the Mamai-Gora burial ground in the Northern Black Sea region (15th century AD). The greatest genetic similarity is observed between the Nogais and other Turkic peoples of the Caucasus, who are located on the periphery of the “Nogai” cluster within the framework of the Caucasian genetic landscape.

Background/Objectives: The eastern periphery of the Slavic expansion (the Volga-Oka region) is the most promising region for reconstructing interactions between Slavic and pre-Slavic populations of the East European Plain. Unlike most pre-Slavic tribes, its autochthonous population practiced inhumation instead of cremation, leaving us with some ancient DNA for analysis. Methods: The region's modern and ancient Y-chromosome gene pools are dominated by the haplogroup R1a: its frequency reaches 56% in Ryazan Russians (n = 302) and 44% in the Finnic peoples of Mordovia (n = 633). This encouraged us to analyze its Y-SNPs and Y-STRs. Results: Using 2 independent methods of phylogeny analysis, we identified 10 informative Y-STR clusters within R1a, dating back 1600-2900 YBP. The clusters included 48% of modern Ryazan Russians, 40% of Mordovia's Finnic populations, and ancient DNA samples from the Ryazan-Oka culture (6-7th centuries), Suzdal (12-13th centuries) and Vladimir (13th century). Such a unique combination and pre-Slavic TMRCA indicate that the informative clusters represent pre-Slavic Y lineages. The presence of ancient samples from Vladimir and Suzdal in the clusters suggests that the autochthonous tribes contributed to shaping the urban population of the Vladimir-Suzdal Rus. Some of the informative clusters are associated with the ancient population of the Baltics (2000-4000 YBP). Conclusions: About half of Russian R1a carriers in the Volga-Oka region are descended from a pre-Slavic population, suggesting that the Slavs did not fully replace the autochthonous population but rather mostly culturally assimilated the Meshchyora documented in the Russian chronicles and other local tribes.

Background: Eastern Finnic populations, including Karelians, Veps, Votes, Ingrians, and Ingrian Finns, are a significant component of the history of Finnic populations, which have developed over ~3 kya. Yet, these groups remain understudied from a genetic point of view. Methods: In this work, we explore the gene pools of Karelians (Northern, Tver, Ludic, and Livvi), Veps, Ingrians, Votes, and Ingrian Finns using Y-chromosome markers (N = 357) and genome-wide autosomes (N = 67) and in comparison with selected Russians populations of the area (N = 763). The data are analyzed using statistical, bioinformatic, and cartographic methods. Results: The autosomal gene pool of Eastern Finnic populations can be divided into two large categories based on the results of the PCA and ADMIXTURE modeling: (a) “Karelia”: Veps, Northern, Ludic, Livvi, and Tver Karelians; (b) “Ingria”: Ingrians, Votes, Ingrian Finns. The Y-chromosomal gene pool of Baltic Finns is more diverse and is composed of four genetic components. The “Northern” component prevails in Northern Karelians and Ingrian Finns, the “Karelian” in Livvi, Ludic, and Tver Karelians, the “Ingrian-Veps” in Ingrians and Veps (a heterogeneous cluster occupying an intermediate position between the “Northern” and the “Karelian” ones), and the “Southern” in Votes. Moreover, our phylogeographic analysis has found that the Y-haplogroup N3a4-Z1927 carriers are frequent among most Eastern Finnic populations, as well as among some Northern Russian and Central Russian populations. Conclusions: The autosomal clustering reflects the major areal groupings of the populations in question, while the Y-chromosomal gene pool correlates with the known history of these groups. The overlap of the four Y-chromosomal patterns may reflect the eastern part of the homeland of the Proto-Finnic gene pool. The carriers of the Y-haplogroup N3a4-Z1927, frequent in the sample, had a common ancestor at ~2.4 kya, but the active spread of N3a4-Z1927 happened only at ~1.7–2 kya, during the “golden” age of the Proto-Finnic culture (the archaeological period of the “typical” Tarand graves). A heterogeneous Y-chromosomal cluster containing Ingrians, Veps, and Northern Russian populations, should be further studied.

The gene pool of the East Caucasus, encompassing modern-day Azerbaijan and Dagestan populations, was studied alongside adjacent populations using 83 Y-chromosome SNP markers. The analysis of genetic distances among 18 populations (N = 2216) representing Nakh-Dagestani, Altaic, and Indo-European language families revealed the presence of three components (Steppe, Iranian, and Dagestani) that emerged in different historical periods. The Steppe component occurs only in Karanogais, indicating a recent medieval migration of Turkic-speaking nomads from the Eurasian steppe. The Iranian component is observed in Azerbaijanis, Dagestani Tabasarans, and all Iranian-speaking peoples of the Caucasus. The Dagestani component predominates in Dagestani-speaking populations, except for Tabasarans, and in Turkic-speaking Kumyks. Each component is associated with distinct Y-chromosome haplogroup complexes: the Steppe includes C-M217, N-LLY22g, R1b-M73, and R1a-M198; the Iranian includes J2-M172(×M67, M12) and R1b-M269; the Dagestani includes J1-Y3495 lineages. We propose J1-Y3495 haplogroup's most common lineage originated in an autochthonous ancestral population in central Dagestan and splits up ~6 kya into J1-ZS3114 (Dargins, Laks, Lezgi-speaking populations) and J1-CTS1460 (Avar-Andi-Tsez linguistic group). Based on the archeological finds and DNA data, the analysis of J1-Y3495 phylogeography suggests the growth of the population in the territory of modern-day Dagestan that started in the Bronze Age, its further dispersal, and the microevolution of the diverged population.

Na Vostochnom Kavkaze prozhivayut bolee 30 narodov, govoryashchih na kavkazskih, iranskih i tyurkskih yazykah. Sliyanie mnogih migracionnyh potokov i slozhnaya populyacionnaya struktura Vostochnogo Kavkaza zatrudnyayut analiz ego genofonda: iz vsekh regionov Kavkaza on naimenee izuchen. Cel' raboty — vyyavit' osnovnye zakonomernosti v izmenchivosti autosomnyh genofondov etogo regiona. Po obshirnym panelyam SNP-markerov izucheno 356 genomov 29 etnosov: 243 genoma 22 narodov Vostochnogo Kavkaza i 113 genomov 7 narodov okruzhayushchih regionov. Bioinformaticheskij analiz proveden metodami predkovyh komponent ADMIXTURE i glavnyh komponent izmenchivosti genofonda (RSA). Vydvinuta gipoteza trekh osnovnyh plastov genofonda Vostochnogo Kavkaza, vzaimodejstvie kotoryh formiruet ego strukturu. «Dagestanskij» plast neset informaciyu o genofonde drevnego avtohtonnogo naseleniya Severnogo Kavkaza. «Iranskij» plast otrazhaet nasledie drevnih i srednevekovyh voln migracij iranoyazychnogo naseleniya: on sostavlyaet tri chetverti genofonda sovremennogo Azerbajdzhana i okolo treti genofonda narodov Dagestana. «Stepnoj» plast fiksiruet slaboe vliyanie evrazijskoj stepi. Vzaimodejstvie trekh geneticheskih plastov lish' kosvenno svyazano s yazykovoj prinadlezhnost'yu narodov, no u kavkazoyazychnyh narodov svyaz' s lingvistikoj proyavlyaetsya yarche. Vyyavleny chetyre geneticheski svoeobraznye gruppy korennogo naseleniya Vostochnogo Kavkaza, kompleks kotoryh dolzhen vklyuchat'sya v harakteristiku ego autosomnogo genofonda: 1) dargincy, lakcy; 2) avarcy, lezginy, tabasarany, aguly, rutul'cy, cahury; 3) kumyki, taty i azerbajdzhancy Dagestana; 4) azerbajdzhancy i talyshi Azerbajdzhana. Opredeleny napravleniya dal'nejshih issledovanij.

Eastern Caucasus is home to more than 30 peoples speaking Caucasian, Iranian and Turkic languages. Fusion of multiple migration flows together with the complex population structure of the Eastern Caucasus make it more difficult to analyze its gene pool: this is the most poorly studied one among all regions of the Caucasus. The study is aimed to identify the main patterns of the autosomal gene pool variation in this region. A total of 356 genomes of 29 ethnic groups were studied using the large panels of SNP markers: 243 genomes of 22 peoples of the Eastern Caucasus and 113 genomes of 7 peoples living in adjacent regions. The bioinformatics analysis involved the use of the ADMIXTURE ancestral component method and the gene pool variability principal component analysis (РСА). The hypothesis of three genetic strata, the interaction of which forms the structure of gene pool of the Eastern Caucasus, was put forward. The “Dagestan” stratum carries information about the gene pool of the ancient autochthonous population of the Eastern Caucasus. The “Iranian” stratum represents the legacy of ancient and middle-aged migrations surges of the Iranian-speaking population: it constitutes three quarters of the gene pool of modern Azerbaijan and about one third of the Dagestan peoples' gene pool. The “Steppe” stratum represents a negligible influence of the Eurasian steppe. Interaction of three genetic strata is only indirectly related to the peoples' linguistic affiliation, however, the association with linguistics is more obvious in the Caucasian-speaking peoples. Four genetically distinct groups of indigenous population of the Eastern Caucasus have been identified, the combination of which should be included in the characteristics of its autosomal gene pool: 1) Dargins, Laks; 2) Avars, Lezghins, Tabasarans, Aghuls, Rutul people, Tsakhur people; 3) Kumyks, Tat people and Azerbaijanis living in Dagestan; 4) Azerbaijanis and Talysh living in Azerbaijan. The directions of further research have been defined.

Significant differences between the gene pools of Russian peoples require the development of ethno- regional adapted pharmacogenetic tests and the identification of priority regions for their implementation. Aim. To develop a genogeographic technology to identify selection effects using the example of biomarkers that are significant for pharmacotherapy of patients with cardiovascular diseases (CVD), using a population biobank and the Pharmacogenetics of Populations of Russia and Adjacent Countries database. Material and methods . Deoxyribonucleic acid (DNA) samples from the Biobank of Northern Eurasia from 20 metapopulations of the indigenous population of the European Russia were studied using two following data sets: 24 pharmacogenetic markers of CVDs (3170 samples); 1 276 191 polymorphic DNA markers of the autosomal genome (1293 samples). For each data set, estimates of interpopulation variability in the gene pool are provided — the difference between these estimates characterizes the selection pressure on each of the 24 CVD biomarkers. A genogeographic atlas has been created, the maps of which demonstrate the selection pressure on each biomarker according to the degree of deviation from the selective- neutral variability of the gene pool. Results. Twenty-four CVD biomarkers are divided into three following classes: those close to selective- neutral variability, those subject to stabilizing and differentiating selection. For each of the 24 CVD biomarkers, genogeographic maps were created that reveal selection effects in each of the 20 metapopulations. Most maps have identified populations that are under differential selection pressure and therefore a priority for the implementation of ethno- regionally adapted pharmacogenetic protocols. Conclusion. Pharmacogenetic markers and populations under differential selection require the development of ethno- regionally adapted pharmacogenetic tests. The created cartographic atlas of selection can serve as the basis for pharmacogenetic studies carried out using genogeographic methods.

Background. Personalised medicine is an avenue to create technologies for individual prognosis of the disease onset and development. The identification of individual gene haplotypes is prerequisite to detecting predispositions to multifactorial diseases. The level of serum 8-oxoguanine is an indicator of genotoxic stress underlying many pathologies.Objectives. A study of associations of mmp12 gene’s polymorphic variant rs652438 and the nature of genome oxidative damage in bronchial asthma.Methods. Genotyping of polymorphic variant rs652438 of gene mmp12 was performed using TaqMan-probe real-time PCR assays. The gene variant association with disease was assessed by odds ratio. The degree of DNA oxidative damage was estimated by 8-oxoguanine serum concentrations determined in monoclonal antibody-based enzyme immunoassays. The StatPro software package with StatTools (Palisade Corporation, USA) was used for statistical data processing.Results. The haplotype and allele frequencies were established for polymorphic locus rs652438 of the mmp12 gene in the control and bronchial asthma cohorts. Heterozygotes were shown to differ significantly; the estimate was 2.3-fold higher in the control vs. bronchial asthma (BA) cohort (p < 0.05). The AA and GG haplotype frequencies did not differ significantly. The minor allele G odds ratio (OR = 0.362, CI 95% 0.134–0.975) suggests its protective effect. This may be associated with a lowering activity of the encoded macrophage metalloelastase enzyme, which results in a poorer extracellular matrix destruction in the bronchial tree. The baseline 8-oxoG levels in the control and BA samples were 6.4 and 9.4 ng/mL, respectively (U = 25, Ucut-off = 23; p >0.05). An in vitro electromagnetic exposure of varying frequency leads to a significant oxidative genomic damage in both cohorts and an earlier reparative depletion in bronchial asthma vs. control.Conclusion. A protective effect of minor allele G against pathology has been demonstrated. Adaptations to oxidative genomic stress in bronchial asthma manifest by an impaired resistance to in vitro high-intensity electromagnetic exposures.

Introduction. The question of whether the Alans left a genetic heritage in the modern population of the North Caucasus, and if they did, which populations carry it in their gene pool, is not only a problem of basic science, but also an acute issue of public discussion. Population genetics can test the hypothesis of preserving the contribution of the thousand-year history of the Alanian tribes to the gene pools of the modern peoples of the Caucasus. Materials and methods. The genomes of 207 individuals (on a panel of 4.5 million markers) were studied: Abkhazians, Adyghes, Balkarians, Georgians, Dargins, Ingush, Kabardians, Kuban Cossacks, Karachays, Nogais (Astrakhan, Kuban, Stavropol), Laks, Southern Russians, Tabasarans, Farsi-speaking populations of Dagestan, Circassians, Chechens, Yaghnobis. The contribution of ancestral components to each of 207 genomes was modeled using the ADMIXTURE method. 140 independent ADMIXTURE models were created, the optimal model with K=11 ancestral components is analyzed and mapped. Results and discussion. A single ancestral component was not found in the gene pools of the peoples in the area of the "metropolis" of the Alans: of the eleven ancestral components, the greatest contribution to the genomes of the alleged "heirs" of the Alans was made by four, which are connected like a puzzle on the periphery of the areas. "Ossetian" and "Nakh" make the greatest contribution to the genomes of Ossetians, Ingush and Chechens, with a significant contribution to the genomes of other peoples of the North Caucasus. The gene pool of the Balkars appears to be complex – with the largest contribution of the "Abkhaz-Adyghe" and with a small contribution of the "Ossetian" and "Nakh" ancestral components. The Karachay gene pool is dominated by its own "Karachai-Nogai" component. An analysis of the structure of the Ossetian gene pool showed that the contribution of the "Ossetian" ancestral component is higher in the southern societies of Ossetians, and some Ossetian societies could have retained the Alan trace to a greater extent. Conclusion. The hypothesis of the presence of a common Alanian heritage in the gene pools of modern peoples living in the area of the Alanian “metropolis” has not been confirmed. If we assume that both ancestral components – "Ossetian" and "Nakh" – reflect the genetic heritage of the Alans, then we will have to admit a set of unlikely events. To solve the problem, it is necessary to analyze ancient DNA from different parts of the Alanian area from different chronological sections. The pharmacogenetic landscape differs from the pattern found throughout the genome. Therefore, a thorough analysis of the pharmacogenetic profile of populations is necessary for the transition to personalized medicine.

The introduction of pharmacogenetic tests among the Russian population faces a fundamental limitation — pronounced genetic differences between populations. The genetic geography of pharmacogenetic markers of deoxyribonucleic acid (DNA) helps to remove these limitations. Aim . To reveal the spatial variation of the gene pools of the indigenous European Russian population in terms of DNA markers that are significant for the pharmacotherapy of cardiovascular diseases (CVDs) using the population biobank collections. Material and methods . A total of 3170 samples from 61 populations of the Biobank of Northern Eurasia, which represents the gene pools of the indigenous Eastern Europe population, were studied using two pharmacogenetic DNA marker arrays as follows: 60 most significant markers and 24 markers associated with CVDs. Using the multivariate statistics and genetic geography, a comparison of gene pool variation was made. Results . A cartographic atlas has been created that includes maps of the distribution among the Eastern Europe population of 24 pharmacogenetic CVD markers. These cartographic models allow various specialists to analyze patterns in the distribution of pharmacogenetic markers. General patterns are supplemented by regional studies in the North Caucasus, the Cisurals and the Russian Plain, which identify population groups with similar pharmacogenetic status. For each region, a comparison of gene pool variation for two arrays of above-mentioned DNA markers was made. Conclusion . The created atlas is the basis for the development of pharmacogenetic studies conducted by genetic geography methods using a single panel of markers and representative samples provided by population biobanks. The reliability of the results is ensured by a detailed genealogical and population annotation of each biobank sample and representative samples from the populations.

The purpose of the study is to evaluate the possibility of preserving the genetic memory of the original architectonics of Adygeans gene pool by studying the modern gene pools of ten clan groups. Materials and methods. Ten tribal populations of Adygeans as well as Ubykhs (total N=616) were studied by a unified informative panel of SNP-markers of Y-chromosome (59 SNP and 17 STR). Genetic portraits of each population were created, and their position in the multidimensional genetic space was evaluated based on the data on the 34 identified Y-haplogroups. For the most characteristic haplogroups, a cartographic analysis was performed and phylogenetic networks were created. Results. Four haplogroups were found in all Adygeans populations, making up three quarters of their general gene pool: G2-YY1215(43%), R1a-M198* (13%), G2-YY9632 (9%), J2-M172* (7%). In the genetic space of the multidimensional scaling were distinguished three clusters: "Western" united all Shapsugs and Ubykhs; "Central" – Abadzekhs, Temirgoevs, Khatukaevs; "Eastern" – Ygerukhaevs, Kabardins of Adygea. Bzhedugs, now a conglomerate of various tribes, occupy precisely an intermediate position between the 'Western' and 'Central' clusters. Mamkhegs and Besleneys were not included in any of the clusters, but joined the "Eastern cluster" by the results of other multivariate analysis methods. The cartographic atlas of the Y-chromosome variability revealed two main trends in the variability: for the haplogroup G2-YY1215 a trend of frequency decrease from west to east (from 82% for Shapsugs to 13% for Kabardins of Adygea), and an opposite trend of a small frequency decrease of G2-YY9632 from east to west. Conclusion. It was shown for the first time that the haplogroup G2-YY1215 is dominant in the gene pool of Adygeans as a whole, as well as in practically all tribal groups. Its frequency decrease from west to east, disappearing already in the Ossetians. The results allow us to consider the haplogroup G2-YY1215 as "marking" the Adyghe population. The revealed three clusters of populations and their relative position in the genetic space correspond to the historical and ethnological data and allow to reconstruct the contours of the initial architectonics of Adygeans. The phylogenetic analysis indicates the presence of a common Adygean "prapopulation" for all tribal groups, which existed about 3000 years ago and demographic growth 1500-2000 years ago.

Nekhvatka informatsii o rasprostranennosti v RF farmakogeneticheskikh markerov privodit k nevozmozhnosti vnedreniya algoritmov personalizatsii, razrabotannykh dlya Zapadnoy Yevropy. Tsel'yu raboty bylo sistematicheskoye izucheniye rasprostranennosti ryada znachimykh farmakogeneticheskikh markerov po vsey territorii Rossii. Iz neskol'kikh massivov populyatsionno-geneticheskikh dannykh otobrany 45 markerov (ADME-genov; genov, kodiruyushchikh farmakodinamicheskiye misheni lekarstvennykh sredstv; genov, kodiruyushchikh komponenty sistemy gemostaza), genotipirovannykh summarno dlya 2197 individov. Opredeleny chastoty etikh markerov v 50 populyatsiyakh, vklyuchayushchikh informatsiyu o 137 etnicheskikh i subetnicheskikh gruppakh. V rezul'tate sozdan farmakogeneticheskiy atlas — sistematicheskoye sobraniye genogeograficheskikh kart rasprostranennosti farmakogeneticheskikh DNK markerov po vsey territorii Rossii i sopredel'nykh stran. Atlas vyyavil tri patterna prostranstvennoy izmenchivosti. Pattern klinal'noy izmenchivosti (gradiyentnogo izmeneniya chastot po osi «vostok–zapad») ob"yedinyayet markery, sleduyushchiye osnovnoy zakonomernosti vsego genofonda naseleniya Severnoy Yevrazii (13% kart atlasa). Pattern ravnomernogo raspredeleniya vydelyayet markery, srednyaya chastota kotorykh kharakterna dlya bol'shinstva regionov Rossii (27% kart atlasa). Pattern «ochagovoy» izmenchivosti ob"yedinyayet farmakogeneticheskiye markery, kharakternyye tol'ko dlya opredelennoy gruppy etnosov i otsutstvuyushchiye v drugikh regionakh (60% kart atlasa). Atlas pokazyvayet, chto srednyaya chastota markera i informatsiya o yego vstrechayemosti v otdel'nykh populyatsiyakh ne mogut sluzhit' ukazaniyem na tip yego raspredeleniya v prostranstve RF — dlya vyyavleniya patterna izmenchivosti neobkhodima genogeograficheskaya karta.

The lack of information about the frequency of pharmacogenetic markers in Russia impedes the adoption of personalized treatment algorithms originally developed for West European populations. The aim of this paper was to study the distribution of some clinically significant pharmacogenetic markers across Russia. A total of 45 pharmacogenetic markers were selected from a few population genetic datasets, including ADME, drug target and hemostasis-controlling genes. The total number of donors genotyped for these markers was 2,197. The frequencies of these markers were determined for 50 different populations, comprised of 137 ethnic and subethnic groups. A comprehensive pharmacogenetic atlas was created, i.e. a systematic collection of gene geographic maps of frequency variation for 45 pharmacogenetic DNA markers in Russia and its neighbor states. The maps revealed 3 patterns of geographic variation. Clinal variation (a gradient change in frequency along the East-West axis) is observed in the pharmacogenetic markers that follow the main pattern of variation for North Eurasia (13% of the maps). Uniform distribution singles out a group of markers that occur at average frequency in most Russian regions (27% of the maps). Focal variation is observed in the markers that are specific to a certain group of populations and are absent in other regions (60% of the maps). The atlas reveals that the average frequency of the marker and its frequency in individual populations do not indicate the type of its distribution in Russia: a gene geographic map is needed to uncover the pattern of its variation.

The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report genome-wide data of two Eneolithic individuals (∽5,400 years before present) associated with the Botai culture in northern Kazakhstan. We find that inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries. This genetic separation is well mirrored by geography. The ancient Botai genomes suggest yet another layer of admixture in inner Eurasia that involves Mesolithic hunter-gatherers in Europe, the Upper Paleolithic southern Siberians and East Asians. Admixture modeling of ancient and modern populations suggests an overwriting of this ancient structure in the Altai-Sayan region by migrations of western steppe herders, but partial retaining of this ancient North Eurasian-related cline further to the North. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.

Ubykh people inhabited the area of what now is Greater Sochi, one time being neighbors of the Abkhaz and Adyghe. In 1864, after the Caucasian War, a small group of Ubykh survivors migrated to Turkey. The Ubykh language is a branch of the Northwest Caucasian (Abkhazo-Adyghe) languages, which is either placed in the Abkhaz or Adyghe subgroup or distinguished in a separate subgroup, according to various classifications. All this makes Ubykhs an important but genetically unexplored part of the gene pool of the Caucasus population. We collected an exclusive sample (N = 36) of Ubykh individuals, mainly from their diaspora in Turkey. Application of a high resolution panel of Y-chromosome markers (59 SNP and 17 STR) revealed the major West Caucasus haplogroup G2 (75% of the Ubykh population) and pan-Eurasian haplogroup R1a (19%). Within the G2 haplogroup, we identified 14 branches and genotyped 14 branch-defining markers. The frequencies of the same 14 markers in 19 other populations of the Caucasus were included for comparison. Both the genetic distances and the gene geographical map of the most frequent subhaplogroup (defined by the YY1215 marker at the GRCh37 position 8903699, comprising 50% of the Ubykh sample) revealed similarity of the Ubykh and Adyghe populations. Other Abkhaz-Adyghe-speaking populations appear to be at a greater genetic distance from the Ubykhs, similar to the distance to the Turkic-speaking groups of the North Caucasus. The Ossetian gene pool has little in common with Ubykhs, thus contradicting the hypothesis of the Alanian substrate in Ubykhs. Other populations of the Caucasus and Transcaucasia (of Nakh-Daghestanian and Kartvelian linguistic groups) do not show apparent genetic similarities to Ubykhs.

Although mutations in the GJB2 gene sequence make up the majority of variants causing autosomal-recessive non-syndromic hearing loss, few large deletions have been shown to contribute to DFNB1 deafness. Currently, genetic testing for DFNB1 hearing loss includes GJB2 sequencing and DFNB1 deletion analysis for two common large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Here, we report frequency in Russia, clinical significance and evolutionary origins of a 101 kb deletion, del(GJB2-D13S175), recently identified by us. In multiethnic cohort of 1104 unrelated hearing loss patients with biallelic mutations at the DFNB1 locus, the del(GJB2-D13S175) allele frequency of up to 0.5% (11/2208) was determined and this allele was shown to be predominantly associated with profound sensorineural hearing loss. Additionally, eight previously unpublished GJB2 mutations were described in this study. All patients carrying del(GJB2-D13S175) were of the Ingush ancestry. Among normal hearing individuals, del(GJB2-D13S175) was observed in Russian Republic of Ingushetia with a carrier rate of ~1% (2/241). Analysis of haplotypes associated with the deletion revealed a common founder in the Ingushes, with age of the deletion being ~3000 years old. Since del(GJB2-D13S175) was missed by standard methods of GJB2 analysis, del(GJB2-D13S175) detection has been added to our routine testing strategy for DFNB1 hearing loss.

Y-chromosomal variation in West Asian populations has so far been studied in less detail than in the neighboring Europe. Here, we analyzed 598 Y-chromosomes from two West Asian subregions—Transcaucasia and the Armenian plateau—using 40 Y-SNPs and 17 Y-STRs and combined them with previously published data from the region. The West Asian populations fell into two clusters: upland populations from the Anatolian, Armenian and Iranian plateaus, and lowland populations from the Levant, Mesopotamia and the Arabian Peninsula. This geographic subdivision corresponds with the linguistic difference between Indo-European and Turkic speakers, on the one hand, and Semitic speakers, on the other. This subdivision could be traced back to the Neolithic epoch, when upland populations from the Anatolian and Iranian plateaus carried similar haplogroup spectra but did not overlap with lowland populations from the Levant. We also found that the initial gene pool of the Armenian motherland population has been well preserved in most groups of the Armenian Diaspora. In view of the contribution of West Asians to the autosomal gene pool of the steppe Yamnaya archaeological culture, we sequenced a large portion of the Y-chromosome in haplogroup R1b samples from present-day East European steppe populations. The ancient Yamnaya samples are located on the “eastern” R-GG400 branch of haplogroup R1b-L23, showing that the paternal descendants of the Yamnaya still live in the Pontic steppe and that the ancient Yamnaya population was not an important source of paternal lineages in present-day West Europeans.