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Allelic frequencies at the three most polymorphic loci of the HLA class II region (DRB1, DQA1 and DQB1) were determined in the Nganasan and Ket, the remnants of the two most ancient groups in the Lower Yenisey River/Taimyr Peninsula region in northern Siberia. By single-stranded conformational polymorphism typing, verified by sequencing, 19 HLA-DRB1-DQA1-DQB1 haplotypes and 15 HLA-DRB1, seven DQA1 and 11 DQB1 alleles were found. The most frequent alleles were DRB1*1301 (23.5%), DQA1*0103 (29.4%), *0501/03/05 (29.4%), and DQB1*0301/09 (32.4%) in the Ket, and DRB1*0901 (25%), DQA1*0301 (39.6%), and DQB1*0301/09 (37.5%) in the Nganasan. The distribution patterns and comprehensive phylogenic analysis based on the haplotype frequencies of 17 Siberian populations suggest that the founders of both the Ket and the Nganasan came from Palaeolithic populations in the Altai-Sayan Upland. [ABSTRACT FROM AUTHOR]

Our data first represent the variety of Leber's hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself as painless central vision loss, resulting in early onset of disability. The epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients. Known "primary" pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53.10% (17/32), m.3460G>A-21.90% (7/32), m.14484T>C-18.75% (6/32), and rare m.10663T>C and m.3635G>A represent 6.25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.6261G>A, m.8412T>C, m.8551T>C, m.9444C>T, m.9921G>A, and m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations., Competing Interests: The authors declare no conflict of interest.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load., (Copyright © 2015, American Association for the Advancement of Science.)

We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans., Competing Interests: The authors have declared that no competing interests exist.

The mtDNA variation has been studied in representatives of the Russkoe Ust'e (n = 30), Kolyma (n = 31), and Markovo (n = 26) ethnic subgroups originating from Russian military men, hunters, and fishers who married local Yukaghir women and settled at the Arctic Ocean coast and on the Anadyr' River more than 350 years ago. The mtDNA haplotypes characteristic of indigenous Siberian peoples have been demonstrated to form the basis of the mitochondrial gene pool of long-term Russian resident populations of the region. Only one of 30 identified haplotypes belonging to 11 haplogroups (H2a) is characteristic of European populations. The C and D haplogroups are the most diverse. The analysis has revealed the characteristics of the population structure of the long-term Russian resident populations and allowed them to be interpreted in terms of recent historical and environmental processes.

The role of natural selection in the evolution of human populations from Northeastern Eurasia was studied. Selection for the regions-specific haplogroup C was demonstrated.

Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of ecoregions and dietary components. These aspects of human environments have changed dramatically during human evolution, giving rise to new selective pressures. To understand the genetic basis of human adaptations, we combine population genetics data with ecological information to detect variants that increased in frequency in response to new selective pressures. Our approach detects SNPs that show concordant differences in allele frequencies across populations with respect to specific aspects of the environment. Genic and especially nonsynonymous SNPs are overrepresented among those most strongly correlated with environmental variables. This provides genome-wide evidence for selection due to changes in ecoregion, diet, and subsistence. We find particularly strong signals associated with polar ecoregions, with foraging, and with a diet rich in roots and tubers. Interestingly, several of the strongest signals overlap with those implicated in energy metabolism phenotypes from genome-wide association studies, including SNPs influencing glucose levels and susceptibility to type 2 diabetes. Furthermore, several pathways, including those of starch and sucrose metabolism, are enriched for strong signals of adaptations to a diet rich in roots and tubers, whereas signals associated with polar ecoregions are overrepresented in genes associated with energy metabolism pathways.

Based on the mtDNA first hypervariable segment sequence variation data, statistical analysis of the diversity in Yukaghirs in comparison with the other indigenous populations of Siberia, was carried out. The level of the Yukaghir mtDNA gene diversity (GD) constituted 0.920, which was only slightly different from the corresponding estimate for the other Siberian populations. Integral estimates of the genetic structure of Siberian populations (k, S, theta(s), and pi) are presented. Phylogenetic analysis, performed using the neighbor-joining method, showed that the Siberian populations clustered irrespectively to their language affiliation. Negative F(s) values found in Yukaghirs pointed to the possible influence of adaptive selection.

The results of clinical, genealogical and molecular investigation of eighteen families with Leber hereditary optic neuropathy (LHON), identified on the territory of Siberia during the period from 1997 to 2005, are presented. Comprehensive analysis of mitochondrial genome variations in probands and their matrilineal relatives revealed the presence of relatively frequent (G11778A, G3460A, and T14484C), as well as rare and new mutations with the established or presumptive pathological effect (T10663C, G363A, C4640T, and A14619G). The G11778A mutation was detected in nine pedigrees (50%), mostly in the families of ethnic Russians. In eight of these families G11778A was found in preferred association with the coding-region substitutions, typical of western Eurasian mtDNA lineage (haplogroup) TJ. On the contrary, the G3460A mutation was detected in the three families belonging to the indigenous Siberian populations (Tuvinians, Altaians, and Buryats). It was associated with clearly different haplotypes of eastern Eurasian haplogroups, C3, D5, and D8. Unexpectedly, the G3460A de novo mutation was found in a large Tuvinian pedigree. At the same time, in eleven out of fourteen families of Caucasoid origin pathogenic mutations in the ND genes were associated with the T4216C and C1542A coding-region mutations, marking the root motif of haplogoup TJ. It is suggested that phylogenetically ancient mutations could have provided their carriers with the adaptive advantages upon the development of Central and Northern Europe at the end of the last glaciation (10 000 to 9 000 years ago), thereby, contributing to the preservation of weekly pathogenic LHON mutations, appearing at specific genetic background.

Variability of the HLA class II genes (alleles of the DRB1, DQA1, and DQB1 loci) was investigated in a sample of Aleuts of the Commanders (n = 31), whose ancestors inhabited the Commander Islands for many thousand years. Among 19 haplotypes revealed in Aleuts of the Commanders, at most eight were inherited from the native inhabitants of the Commander Islands. Five of these haplotypes (DRB1*0401-DQA1*0301-DQB1*0301, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*0802-DQA1*0401-DQB1*0402, DRB1*1101-DQA1*0501-DQB1*0301, and DRB1*1201-DQA1*0501-DQB1*0301) were typical of Beringian Mongoloids, i.e., Coastal Chukchi and Koryaks, as well as Siberian and Alaskan Eskimos. Genetic contribution of the immigrants to the genetic pool of proper Aleuts constituted about 52%. Phylogenetic analysis based on Transberingian distribution of the DRB1 allele frequencies favored the hypothesis on the common origin of Paleo-Aleuts, Paleo-Eskimos, and the Indians from the northwestern North America, whose direct ancestors survived in Beringian/southwestern Alaskan coastal refugia during the late Ice Age.

Mitochondrial DNA (mtDNA) variation was studied in 38 Kets and 24 Nganasans, the indigenous inhabitants of the north of the Yenisey River Basin and the Taimyr Peninsula. The results were compared with the analogous data obtained for 59 Kondinski and 39 Sos'vinski Mansi. As a whole, mitochondrial gene pool of Mansi, Nganasans, and Kets was characterized by unique combination of European-specific (H, H2, H3, H8, U2, U4, U5, U7, J2, and W) and Asian-specific (A, C, D, and Z) mtDNA haplogroups. Specific features of the haplogroup geographical distribution along with the results of phylogenetic reconstruction favor the hypothesis of the genetic trace left in Eastern Cis-Urals and the adjacent Siberian territories by early migrations from the Near East.

To date, more than 100 point mutations and several hundreds of structural rearrangements of mitochondrial DNA (mtDNA) are known too be connected with characteristic neuromuscular and other mitochondrial syndromes varying form those causing death at the neonatal stage to diseases with late ages of onset. The immediate cause of mitochondrial disorders is a defective oxidative phosphorylation. Wide phenotypic variation and the heteroplasmy phenomenon, which some authors include in mutation load, are characteristic of human mitochondrial diseases. As the numbers of cases identified and pedigrees described increase, data on the genotype--phenotype interaction and the structure and frequency of pathogenic and conditionally pathogenic mtDNA mutations in human populations are rapidly accumulated. The data on the genetics and epidemiology of mitochondrial diseases are not only important for differential diagnosis and genetic counseling. Since both neutral and mildly pathogenic mutations of mtDNA are progressively accumulated in maternal phyletic lines, molecular analysis of these mutations permits not only reconstruction of the genealogical tree of modern humans, but also estimation of the role that these mutations play in natural selection.

Leber's hereditary optic neuropathy (LHON) is characterized by maternally transmitted, bilateral, central vision loss in young adults. It is caused by mutations in the mitochondrial DNA (mtDNA) encoded genes that contribute polypeptides to NADH dehydrogenase or complex I. Four mtDNA variants, the nucleotide pair (np) 3460A, 11778A, 14484C, and 14459A mutations, are known as "primary" LHON mutations and are found in most, but not all, of the LHON families reported to date. Here, we report the extensive genetic and biochemical analysis of five Russian families from the Novosibirsk region of Siberia manifesting maternally transmitted optic atrophy consistent with LHON. Three of the five families harbor known LHON primary mutations. Complete sequence analysis of proband mtDNA in the other two families has revealed novel complex I mutations at nps 3635A and 4640C, respectively. These mutations are homoplasmic and have not been reported in the literature. Biochemical analysis of complex I in patient lymphoblasts and transmitochondrial cybrids demonstrated a respiration defect with complex-I-linked substrates, although the specific activity of complex I was not reduced. Overall, our data suggests that the spectrum of mtDNA mutations associated with LHON in Russia is similar to that in Europe and North America and that the np 3635A and 4640C mutations may be additional mtDNA complex I mutations contributing to LHON expression.

In this study, we analyzed the mitochondrial DNA (mtDNA) variation in 202 individuals representing one Itel'men and three Koryak populations from different parts of the Kamchatka peninsula. All mtDNAs were subjected to high resolution restriction (RFLP) analysis and control region (CR) sequencing, and the resulting data were combined with those available for other Siberian and east Asian populations and subjected to statistical and phylogenetic analysis. Together, the Koryaks and Itel'men were found to have mtDNAs belonging to three (A, C, and D) of the four major haplotype groups (haplogroups) observed in Siberian and Native American populations (A-D). In addition, they exhibited mtDNAs belonging to haplogroups G, Y, and Z, which were formerly called "Other" mtDNAs. While Kamchatka harbored the highest frequencies of haplogroup G mtDNAs, which were widely distributed in eastern Siberian and adjacent east Asian populations, the distribution of haplogroup Y was restricted within a relatively small area and pointed to the lower Amur River-Sakhalin Island region as its place of origin. In contrast, the pattern of distribution and the origin of haplogroup Z mtDNAs remained unclear. Furthermore, phylogenetic and statistical analyses showed that Koryaks and Itel'men had stronger genetic affinities with eastern Siberian/east Asian populations than to those of the north Pacific Rim. These results were consistent with colonization events associated with the relatively recent immigration to Kamchatka of new tribes from the Siberian mainland region, although remnants of ancient Beringian populations were still evident in the Koryak and Itel'men gene pools.

The mtDNAs of 145 individuals representing the aboriginal populations of Chukotka-the Chukchi and Siberian Eskimos-were subjected to RFLP analysis and control-region sequencing. This analysis showed that the core of the genetic makeup of the Chukchi and Siberian Eskimos consisted of three (A, C, and D) of the four primary mtDNA haplotype groups (haplogroups) (A-D) observed in Native Americans, with haplogroup A being the most prevalent in both Chukotkan populations. Two unique haplotypes belonging to haplogroup G (formerly called "other" mtDNAs) were also observed in a few Chukchi, and these have apparently been acquired through gene flow from adjacent Kamchatka, where haplogroup G is prevalent in the Koryak and Itel'men. In addition, a 16111C-->T transition appears to delineate an "American" enclave of haplogroup A mtDNAs in northeastern Siberia, whereas the 16192C-->T transition demarcates a "northern Pacific Rim" cluster within this haplogroup. Furthermore, the sequence-divergence estimates for haplogroups A, C, and D of Siberian and Native American populations indicate that the earliest inhabitants of Beringia possessed a limited number of founding mtDNA haplotypes and that the first humans expanded into the New World approximately 34,000 years before present (YBP). Subsequent migration 16,000-13,000 YBP apparently brought a restricted number of haplogroup B haplotypes to the Americas. For millennia, Beringia may have been the repository of the respective founding sequences that selectively penetrated into northern North America from western Alaska.

Restriction polymorphism of mitochondrial DNA (mtDNA) isolated from the blood of 107 Koryaks, 28 Northern Altaians, and 23 Kets was studied. The results were compared with similar data that in aggregate characterized haplotypes of 569 individual DNAs from 13 Siberian populations, in order to elucidate the genetic similarity and differences between mtDNA haplogroups of native Siberians and Americans. Natives of Siberia are distinguished by the significant variation of the composition and frequency of three (A, C, and D) of four haplogroups characteristic of American Indians. In the full composition, all four haplogroups-A, B, C, and D-are found only in a sample of Northern Altaians. The peculiarities of their geographical distribution in Asia allow us to consider the southern regions of Siberia and the adjacent territories of Central and East Asia as the site inhabited by the ancestors of the first wave of migrants to North America.

The VNTR loci D7S104, D11S129, D18S17, D20S15, and D21S112 in three indigenous Siberian populations were analyzed to determine the populations' genetic structure. Using the Kolmogorov-Smirnov test, we found that the Siberian indigenous populations of Surinda and Sulamai are separated at the D11S129 locus (p < 0.05). However, the population of Poligus is genetically homogeneous compared with the villages of Sulamai and Surinda. Principal component plots for the sets of VNTR loci cluster the Siberian groups together, reflecting the homogeneity of these populations. An analysis of mean per locus heterozygosity versus the distance from the centroid of distribution suggests gene flow into Sulamai but little genetic exchange with Surinda and Poligus. Ultimately, the VNTR data reflect the genetic distinctiveness of the Kets and the Evenki.

This study presents physical fitness data on two indigenous Siberian populations, the Evenki and Keto. The Canadian Aerobic Test of Fitness (CATF) was utilized to provide estimates of maximal oxygen consumption (V̇O 2 max) for a sample of 44 subjects (30 males, 14 females) as baseline data for further studies on changing fitness levels and the health problems associated with acculturation. Estimates of V̇O 2 max average 46.2 ml kg -1 min -1 for males and 33.9 ml kg -1 min -1 for females. These values are comparable to those previously reported for other semisubsistence, cold adapted populations. The Siberian groups are below the Canadian norms in the 15-19 year age range, and thereafter track at about the 50th percentile throughout adulthood. This suggests that the cardiorespiratory systems of adult Evenki and Keto are functionally comparable to the average adult Canadian. © 1994 Wiley-Liss, Inc., (Copyright © 1994 Wiley-Liss, Inc., A Wiley Company.)

The mtDNA variation of 411 individuals from 10 aboriginal Siberian populations was analyzed in an effort to delineate the relationships between Siberian and Native American populations. All mtDNAs were characterized by PCR amplification and restriction analysis, and a subset of them was characterized by control region sequencing. The resulting data were then compiled with previous mtDNA data from Native Americans and Asians and were used for phylogenetic analyses and sequence divergence estimations. Aboriginal Siberian populations exhibited mtDNAs from three (A, C, and D) of the four haplogroups observed in Native Americans. However, none of the Siberian populations showed mtDNAs from the fourth haplogroup, group B. The presence of group B deletion haplotypes in East Asian and Native American populations but their absence in Siberians raises the possibility that haplogroup B could represent a migratory event distinct from the one(s) which brought group A, C, and D mtDNAs to the Americas. Our findings support the hypothesis that the first humans to move from Siberia to the Americas carried with them a limited number of founding mtDNAs and that the initial migration occurred between 17,000-34,000 years before present.

Northern Sel'kup people residing in the upper Taz and the tributaries of Turukhan Rivers were typed for immunoglobulin heavy chain (GM) allotypes. The Sel'kups exhibited a unique GM*-G haplotype circulating within the tribe in low but almost polymorphic frequency along with common GM*F B and GM*A T haplotypes, the former a Caucasian marker and the latter a northern Oriental population's marker. Contemporary Sel'kups show a higher frequency of GM*A T than the westwardly situated Forest Nentsi, reflecting recent historical events in the region such as admixture with the Evenki of Middle Siberia. Within the area located between lower Ob and Yenisey rivers, the unique GM*-N B haplotype, restricted to the Forest Nentsi, and the unique GM*-N' G haplotype, restricted to the Sel'kups, serve as GM markers discriminating between these two adjacent tribes.

The relationship between heterozygosity of 9 polymorphic loci and fertility of women surviving beyond the menopause was studied in the North-Siberian tribe Eveny. The number of pregnancies negatively correlated with the individual heterozygosity (r = -0.2913 + 0.1302, P less than 0.05). Drastic fertility reduction in heterozygous women was observed for G1M, ACP and HP loci.

Three separate and reproductively isolated populations living at present in boreal forest and tundra area in Eastern Siberia were studied. Blood groups (AB0, MNSs, Rhesus, Duffy, P. Diego), immunoglobulin allotypes--G1m (z, a, x, f), G3m (b, b0, b1, b3, s, t), Hp, Tf, PGM1, AcP, 6-PGD were tested in blood samples obtained from total 570 individuals. Analysis of covariance and variance matrices containing gene frequencies of the Nganasans, Reindeer Chukchi, the Yugaghir and the Evens has revealed major aspects of regional genetic structure which is in good accordance with regional history and geography.

Demographic data of genetic interest were studied in three separate populations of Tungus-speaking Evens. They are characterized as expanding populations, rather as a result of migration and admixture, than due to natural increase. The mean and variance of livebirths per female, whose reproduction was completed, were 7.23 and 13.07, respectively. The Crow's index of the opportunity for selection (It) and its components (Im and If) were found to be 0.62, 0.30 and 0.25, respectively. The values of Im and If appeared to be essentially lower than those previously found in other northern populations.