Impact of cross-ancestry genetic architecture on GWASs in admixed populations

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Mitochondrial DNA variation in two South Siberian Aboriginal populations: implications for the genetic history of North Asia

The mtDNAs of 76 individuals representing the aboriginal populations of South Siberia, the Tuvinians and Buryats, were subjected to restriction fragment length polymorphism (RFLP) analysis and control region hypervariable segment I (HVS-I) sequencing, and the resulting data were combined with those available for other Siberian and East Asian populations and subjected to statistical and phylogenetic analysis. This analysis showed that the majority of the Tuvinian and Buryat mtDNAs (94.4% and 92.5%, respectively) belong to haplogroups A, B, C, D, E, F, and M*, which are characteristic of Mongoloid populations. Furthermore, the Tuvinians and Buryats harbor four Asian- and Native American-specific haplogroups (A-D) with frequencies (72.2% and 55%, respectively) exceeding those reported previously for Mongolians, Chinese, and Tibetans. They represent, therefore, the populations that are most closely related to New World indigenous groups. Despite their geographical proximity, the Tuvinians and Buryats shared no HVS-I sequences in common, although individually they shared such sequences with a variety of other Siberian and East Asian populations. In addition, phylogenetic and principal component analyses data of mtDNA sequences show that the Tuvinians clustered more closely with Turkic-speaking Yakuts, whereas the Mongolic-speaking Buryats clustered closer to Korean populations. Furthermore, HVS-I sequences, comprising one-fourth of the Buryat lineages and characterized by the only C-to-T transition at nucleotide position 16223, were identified as different RFLP haplotypes (B, C, D, E, M*, and H). This finding appears to indicate the putative ancestral state of the 16223T HVS-I sequences to Mongoloid macrohaplogroup M, at least. Finally, the results of nucleotide diversity analysis in East Asian and Siberian populations suggest that Central and East Asia were the source areas from which the genetically heterogeneous Tuvinians and Buryats first emerged.     

Mating patterns amongst Siberian reindeer herders: inferences from mtDNA and Y-chromosomal analyses

The Evenks and Evens, who speak closely related languages belonging to the Northern Tungusic branch of the Tungusic family, are nomadic reindeer herders and hunters. They are spread over an immense territory in northeastern Siberia, and consequently different subgroups are in contact with diverse peoples speaking Samoyedic, Turkic, Mongolic, Chukotka-Kamchatkan, and Yukaghir languages. Nevertheless, the languages and culture of the Evenks and Evens are similar enough for them to have been classified as a single ethnic group in the past. This linguistic and cultural similarity indicates that they may have spread over their current area of habitation relatively recently, and thus may be closely related genetically. On the other hand, the great distances that separate individual groups of Evens and Evenks from each other might have led to preferential mating with geographic neighbors rather than with linguistically related peoples. In this study, we assess the correlation between linguistic and genetic relationship in three different subgroups of Evenks and Evens, respectively, via mtDNA and Y-chromosomal analyses. The results show that there is some evidence of a common origin based on shared mtDNA lineages and relatively similar Y-haplogroup frequencies amongst most of the Evenk and Even subgroups. However, there is little sharing of Y-chromosomal STR haplotypes, indicating that males within Evenk and Even subgroups have remained relatively isolated. There is further evidence of some female admixture in different Even subgroups with their respective geographic neighbors. However, the Tungusic groups, and especially the Evenks, show signs of genetic drift, making inferences about their prehistory difficult.     

Mitochondrial DNA origins of the Latvian clefting population

Latvia has one of the highest prevalence of isolated cleft lip with or without cleft palate (CL/P) in Europe. To clarify the genetic origins of the Latvian cleft population and establish a method for genetic mapping, mitochondrial DNA variation was studied in a population affected with clefting. One-hundred and seven subjects and 351 samples from unrelated healthy volunteers representing four anthropologically, archaeologically and ethno-linguistically different regions of Latvia were selected. The case group showed a higher frequency of haplogroups U4 (p=0.02) and U5 (p=0.0003) than in non-U haplogroups. We hypothesize that U4 and U5 mtDNA haplotype carriers may also carry susceptibility genes for clefts. Future studies will take into consideration these definitions based on mtDNA haplotypes when analyzing genetic variations and their possible contribution to CL/P susceptibility.     

Robust estimation of local genetic ancestry in admixed populations using a nonparametric bayesian approach

We present a new haplotype-based approach for inferring local genetic ancestry of individuals in an admixed population. Most existing approaches for local ancestry estimation ignore the latent genetic relatedness between ancestral populations and treat them as independent. In this article, we exploit such information by building an inheritance model that describes both the ancestral populations and the admixed population jointly in a unified framework. Based on an assumption that the common hypothetical founder haplotypes give rise to both the ancestral and the admixed population haplotypes, we employ an infinite hidden Markov model to characterize each ancestral population and further extend it to generate the admixed population. Through an effective utilization of the population structural information under a principled nonparametric Bayesian framework, the resulting model is significantly less sensitive to the choice and the amount of training data for ancestral populations than state-of-the-art algorithms. We also improve the robustness under deviation from common modeling assumptions by incorporating population-specific scale parameters that allow variable recombination rates in different populations. Our method is applicable to an admixed population from an arbitrary number of ancestral populations and also performs competitively in terms of spurious ancestry proportions under a general multiway admixture assumption. We validate the proposed method by simulation under various admixing scenarios and present empirical analysis results from a worldwide-distributed dataset from the Human Genome Diversity Project.     

Mitochondrial DNA variation and the origins of the Aleuts

The mitochondrial DNA (mtDNA) variation in 179 Aleuts from five different islands (Atka, Unalaska, Umnak, St. Paul, and St. George) and Anchorage was analyzed to better understand the origins of Aleuts and their role in the peopling of the Americas. Mitochondrial DNA samples were characterized using polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing of the first hypervariable segment (HVS-I) of the control region. This study showed that Aleut mtDNAs belonged to two of the four haplogroups (A and D) common among Native Americans. Haplogroup D occurred at a very high frequency in Aleuts, and this, along with their unique HVS-I sequences, distinguished them from Eskimos, Athapaskan Indians, and other northern Amerindian populations. While sharing several control region sequences (CIR11, CHU14, CIR60, and CIR61) with other circumarctic populations, Aleuts lacked haplogroup A mtDNAs having the 16265G mutation that are specific to Eskimo populations. R-matrix and median network analyses indicated that Aleuts were closest genetically to Chukotkan (Chukchi and Siberian Eskimos) rather than to Native American or Kamchatkan populations (Koryaks and Itel'men). Dating of the Beringian branch of haplogroup A (16192T) suggested that populations ancestral to the Aleuts, Eskimos, and Athapaskan Indians emerged approximately 13,120 years ago, while Aleut-specific A and D sublineages were dated at 6539 +/- 3511 and 6035 +/- 2885 years, respectively. Our findings support the archaeologically based hypothesis that ancestral Aleuts crossed the Bering Land Bridge or Beringian platform and entered the Aleutian Islands from the east, rather than island hopping from Kamchatka into the western Aleutians. Furthermore, the Aleut migration most likely represents a separate event from those responsible for peopling the remainder of the Americas, meaning that the New World was colonized through multiple migrations.     

Mitochondrial DNA diversity in Siberian Tatars of the Tobol-Irtysh basin

Data on the variation of the nucleotide sequence of hypervariable segment I (HVSI) and restriction fragment length polymorphism (RFLP) of the coding region of mitochondrial DNA (mtDNA) have been used to characterize the mitochondrial gene pool of Siberian Tatars of the Tobol-Irtysh basin (N = 218), one of three geographic/linguistic groups of Siberian Tatars. The gene pool of Siberian Tatars has been shown to contain both Asian and European mtDNA lineages at a ratio of 1.0 : 1.5. The mtDNA diversity of Siberian Tatars is substantially higher than that of other Turkic-speaking populations of North and Central Asia. The position of the mitochondrial gene pool of Tatars of the Tobol-Irtysh basin in the genetic space of northern Eurasia populations has been determined.     

Mitochondrial DNA diversity in Siberian Tatars of the Tobol-Irtysh basin

Data on the variation of the nucleotide sequence of hypervariable segment I (HVSI) and restriction fragment length polymorphism (RFLP) of the coding region of mitochondrial DNA (mtDNA) have been used to characterize the mitochondrial gene pool of Siberian Tatars of the Tobol-Irtysh basin (N = 218), one of three geographic/linguistic groups of Siberian Tatars. The gene pool of Siberian Tatars has been shown to contain both Asian and European mtDNA lineages at a ratio of 1 : 1.5. The mtDNA diversity of Siberian Tatars is substantially higher than that of other Turkic-speaking populations of North and Central Asia. The position of the mitochondrial gene pool of Tatars of the Tobol-Irtysh basin in the genetic space of northern Eurasia populations has been determined.     

Mitochondrial DNA HVRI variation in Balearic populations

The Balearic archipelago (Majorca, Minorca, and Ibiza islands and the Chuetas, a small and inbred community of descendants of Sephardic Jews) and Valencia were studied by means of the sequencing of a 404-bp segment of hypervariable region I (HVRI) mtDNA in 231 individuals. In total, 127 different haplotypes defined by 92 variable positions were identified. The incidence of unique haplotypes was very low, especially in Ibiza and the Chuetas. A remarkable observation in the Chueta community was the high frequency (23%) of preHV-1, a Middle Eastern lineage that is closely related, though not identical, to many others found at high frequencies in different Jewish populations. The presence of this haplogroup convincingly supported the Jewish origin of the Chueta community. The studied populations showed a reduced African contribution, and no individuals were detected with North African haplogroup U6, indicating a lack of maternal contribution from the Moslem settlement to these populations. Only Ibiza showed a lower diversity, indicating a possible genetic drift effect, also supported by the historical information known about this island. The variability in the sequence of mtDNA hypervariable region I correlated well with the existing information from the populations, with the exception of that of the Y-chromosome, which could indicate a differential contribution of the maternal and paternal lineages to the genetic pool of the Balearic Islands. The phylogenetic trees showed the intermediate position of the Chueta population between the Middle Eastern and Majorcan samples, confirming the Jewish origin of this population and their Spanish admixture.     

Mitochondrial DNA,chloroplast DNA and the origins of development in eukaryotic organisms

Background  

Several proposals have been made to explain the rise of multicellular life forms. An internal environment can be created and controlled, germ cells can be protected in novel structures, and increased organismal size allows a "division of labor" among cell types. These proposals describe advantages of multicellular versus unicellular organisms at levels of organization at or above the individual cell. I focus on a subsequent phase of evolution, when multicellular organisms initiated the process of development that later became the more complex embryonic development found in animals and plants. The advantage here is realized at the level of the mitochondrion and chloroplast.     

Mitochondrial DNA D‐loop sequence analysis reveals high variation and multiple maternal origins of indigenous Tanzanian goat populations

The Small East African (SEA) goat are widely distributed in different agro‐ecological zones of Tanzania. We report the genetic diversity, maternal origin, and phylogenetic relationship among the 12 Tanzanian indigenous goat populations, namely Fipa, Songwe, Tanga, Pwani, Iringa, Newala, Lindi, Gogo, Pare, Maasai, Sukuma, and Ujiji, based on the mitochondrial DNA (mtDNA) D‐loop. High haplotype (H _d = 0.9619–0.9945) and nucleotide (π = 0.0120–0.0162) diversities were observed from a total of 389 haplotypes. The majority of the haplotypes (n = 334) belonged to Haplogroup A which was consistent with the global scenario on the genetic pattern of maternal origin of all goat breeds in the world. Haplogroup G comprised of 45 haplotypes drawn from all populations except the Ujiji goat population while Haplogroup B with 10 haplotypes was dominated by Ujiji goats (41%). Tanzanian goats shared four haplotypes with the Kenyan goats and two with goats from South Africa, Namibia, and Mozambique. There was no sharing of haplotypes observed between individuals from Tanzanian goat populations with individuals from North or West Africa. The indigenous goats in Tanzania have high genetic diversity defined by 389 haplotypes and multiple maternal origins of haplogroup A, B, and G. There is a lot of intermixing and high genetic variation within populations which represent an abundant resource for selective breeding in the different agro‐ecological regions of the country.     

Mitochondrial DNA diversity and origins of South and Central American goats

We have analysed the genetic diversity of South and Central American (SCA) goats by partially sequencing the mitochondrial control region of 93 individuals with a wide geographical distribution. Nucleotide and haplotype diversities reached values of 0.020 ± 0.00081 and 0.963 ± 0.0012 respectively. We have also observed a rather weak phylogeographic structure, with almost 69% of genetic variation included in the within-breed variance component. The topology of a median-joining network analysis including 286 European, Iberian, Atlantic and SCA mitochondrial sequences was very complex, with most of the haplotypes forming part of independent small clusters. SCA sequences showed a scattered distribution throughout the network, and clustering with Spanish and Portuguese sequences occurred only occasionally, not allowing the distinguishing of a clear Iberian signature. Conversely, we found a prominent cluster including Canarian, Chilean, Argentinian and Bolivian mitochondrial haplotypes. This result was independently confirmed by constructing a Bayesian phylogenetic tree (posterior probability of 0.97). Sharing of mitochondrial haplotypes by SCA and Canarian goats suggests that goat populations from the Atlantic archipelagos, where Spanish and Portuguese ships en route to the New World used to stow food and supplies, participated in the foundation of SCA caprine breeds.     

Mitochondrial DNA variation in European populations of Silurus glanis

Mitochondrial DNA diversity of 13 wild Silurus glanis populations (covering the entire range of the species) and eight hatchery populations was investigated. PCR-RFLP analysis of four regions of mitochondrial DNA (cytochrome b, control region, ND-5/6) was used. Nineteen haplotypes were found. Thirteen of them were private. The proportion of total genetic diversity attributable to population differentiation was almost 80%. Despite the existence of significant differentiation between populations for mtDNA variation, no consistent pattern of geographic structuring was revealed and nucleotide divergence among S. glanis populations was low. These phenomena are discussed with regard to the impact of glaciation events. The domesticated stocks show less genetic diversity than natural ones, possibly due to their mode of management. Analysis of three European catfish species S. glanis, S. aristotelis and Silurus triostegus (sampled in the Euphrates river) revealed several endonucleases which produced restriction phenotypes diagnostic for the three species.     

Mitochondrial DNA variability of West New Guinea populations.

This paper reports human mitochondrial DNA variability in West New Guinea (the least known, western side of the island of New Guinea), not yet described from a molecular perspective. The study was carried out on 202 subjects from 12 ethnic groups, belonging to six different Papuan language families, representative of both mountain and coastal plain areas. Mitochondrial DNA hypervariable region 1 (HVS 1) and the presence of the 9-bp deletion (intergenic region COII-tRNA(Lys)) were investigated. HVS 1 sequencing identified 73 polymorphic sites defining 89 haplotypes; the 9-bp deletion, which is considered a marker of Austronesian migration in the Pacific, was found to be absent in the whole West New Guinea study sample. Statistical analysis applied to the resulting haplotypes reveal high heterogeneity and an intersecting distribution of genetic variability in these populations, despite their cultural and geographic diversity. The results of subsequent phylogenetic approaches subdivide mtDNA diversity in West New Guinea into three main clusters (groups I-III), defined by sets of polymorphisms which are also shared by some individuals from Papua New Guinea. Comparisons with worldwide HVS 1 sequences stored in the MitBASE database show the absence of these patterns outside Oceania and a few Indonesian subjects, who also lack the 9-bp deletion. This finding, which is consistent with the effects of genetic drift and prolonged isolation of West New Guinea populations, lead us to regard these patterns as New Guinea population markers, which may harbor the genetic memory of the earliest human migrations to the island.