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Post by Admin on May 3, 2014 1:27:10 GMT
The Uyghur (UIG) population, settled in Xinjiang, China, is a population presenting a typical admixture of Eastern and Western anthropometric traits. We dissected its genomic structure at population level, individual level, and chromosome level by using 20,177 SNPs spanning nearly the entire chromosome 21. Our results showed that UIG was formed by two-way admixture, with 60% European ancestry and 40% East Asian ancestry. Overall linkage disequilibrium (LD) in UIG was similar to that in its parental populations represented in East Asia and Europe with regard to common alleles, and UIG manifested elevation of LD only within 500 kb and at a level of 0.1 < r2 < 0.8 when ancestry-informative markers (AIMs) were used. The size of chromosomal segments that were derived from East Asian and European ancestries averaged 2.4 cM and 4.1 cM, respectively. Both the magnitude of LD and fragmentary ancestral chromosome segments indicated a long history of Uyghur. Under the assumption of a hybrid isolation (HI) model, we estimated that the admixture event of UIG occurred about 126 [107∼146] generations ago, or 2520 [2140∼2920] years ago assuming 20 years per generation. In spite of the long history and short LD of Uyghur compared with recent admixture populations such as the African-American population, we suggest that mapping by admixture LD (MALD) is still applicable in the Uyghur population but ∼10-fold AIMs are necessary for a whole-genome scan. Principal-coordinate analysis (PCO) provides a useful means of revealing relationships among individuals. Figure 2 is a two-dimensional plot displaying the first two PCO axes for all individuals, with allele-sharing distance (ASD) used for all pairwise combinations of individuals. Individuals from one population cluster tightly, to the exclusion of individuals from other populations. The first two axes together explain 25.8 % of the total variation, and each of the remaining axes explains less than 1.5 % of the total variation. The first PCO axis shows a separation of the African and non-African populations and explains 17.57 % of the total variation; the second PCO axis explains 8.27 % of the total variation and shows a separation of the European and East Asian populations, with UIG individuals lying between them. This is also an expected result of UIG as an admixed population. Figure 2. Principal-Coordinate-Analysis Representation of the Allele-Sharing Distance Populations included are indicated by the symbols listed in the legend. The first two axes together explain 25.8 percent of the total variation (17.57 percent by the first axis and 8.27 percent by the second), and the rest of the axes each explain less than 1.5 percent of the total variation.Using selected AIMs, we further inferred the ancestral origins of chromosomal segments in 40 UIG individuals. We selected a panel of 83 AIMs encompassing an overall area of 63.37 cM on chromosome 21 for estimation of the ancestry of alleles. The STRUCTURE program49 was run under the linkage model with the option of correlated allele frequency. The estimated haplotypes from the 40 UIG individuals were examined together with the phased data from the 60 CEU and 45 CHB subjects under a two-population model (K = 2). Figure 7. Inferred Ancestral Origins of a 67.37 cM Segment of Chromosome 21 in Three Populations Each column represents a population. The first column shows 60 CEU subjects, the second column shows 40 UIG subjects, and the third column shows 45 CHB subjects. Chromosome pairs are depicted with spaces between individual subjects. The Ln of the ratio of the probability that each locus on each haplotype in each individual derived from either Asian or European ancestry was determined for each individual and coded as red (Ln Asian/European > 1.0), blue (Ln Asian/European < −1.0), or gray lines (Ln Asian/European < 1.0, > −1.0). The marker positions (Rutgers map) are depicted in the bottom of UIG plot, and are the same in the three populations.With the assumption that East Asian and European populations were the only two parental populations, STRUCTURE provided the probability of an allele being derived from either the East Asian cluster or the European cluster. The natural logarithms of the probability ratio (LnPR) that an allele was derived from the East Asian cluster over the European cluster were estimated, and the results are depicted in Figure 7. The results provide information on the ancestry of the chromosome segments for each individual (see Supplemental Data for details). As expected, the UIG haplotypes showed contributions from both parental populations (Figure 7). The contribution from European ancestry was greater than that from East Asian ancestry in UIG. The mean contributions of ancestry were 60% (minimum 40.3% and maximum 84.3%) from European ancestry and 40% (minimum 15.7% and maximum 59.7%) from East Asian ancestry. Some segments existed for which ancestry was uncertain (shown in gray in Figure 7), because it is difficult to precisely define the length of the segments in UIG derived from each population sample. Notably, most ambiguous segments were distributed in the region with few or even no AIMs (AIM “deserts”). The cumulative frequencies of segment sizes that were derived from East Asian ancestry and from European ancestry are shown in Figure S7. The first quartile of segment size with East Asian ancestry was 0.55 cM, the second quartile was 1.68 cM, and the third quartile was 3.24 cM. For chromosomal segments with European ancestry, the first quartile of segment size was 0.83 cM, the second quartile was 3.14 cM, and the third quartile was 5.09 cM. The average sizes of chromosomal segments that were derived from East Asian ancestry and European ancestry were 2.43 cM and 4.07 cM, respectively. At the chromosomal level, we inferred the ancestral origins of UIG chromosome segments: the average size of chromosome segments that were derived from East Asian and European populations were 2.4 cM and 4.1 cM, respectively. The estimated recombination rate was about 1.07–1.46 breakpoints per cM. Under the assumption of a hybrid-isolation (HI) model, the admixture event of UIG was estimated to have taken place about 107–146 generations, or 2140–2920 years ago assuming 20 years per generation. The word “Uyghur” (alternatively Uygur, Uigur, and Uighur) originates from the Old Turkish word “Uyγur.” On the basis of its Old Turkish phonetics, the word “Uyγur” was rendered differently in Chinese during different periods of China's history. The most ancient translation of the word “Uyγur” in Chinese was “Yuanhe,” which appears in Weishu (History of the Wei Dynasty), which was compiled during the period of Northern Qi (550–577 AD). The ancestors of the Uyghur (Gaoche) can be traced to the Chidi and Dingling in the third century B.C. (See Sima Qian, ‘Shiji’ Vol. 110: Xiongnu). Therefore, the estimated admixture time could be concordant with the historical record. However, this result could be underestimated due to the assumption of a hybrid-isolation (HI) model. In this model, we assumed that Uyghur was formed by a single event of admixture during a short period of time, which might not be true of the real history of the Uyghur. Considering the geographical location where the Uyghur settled, continuous gene flow from populations of European and Asian descent was very likely. Because the time estimation in this study was based on the information of recombination or linkage disequilibrium (LD), which decays with time of generations, LD could have been maintained to some extent, and recombination information could have been diluted if there had been continuous gene flow; thus, the time of admixture could be underestimated. In addition, the time of admixture could be underestimated because the distribution of the length of chromosome segments might be biased toward large segments due to the large spacing between markers and the uncertainty in the ancestry estimation of some alleles. Furthermore, switch errors are almost inevitable when haplotypes are inferred from genotype data of unrelated individuals. For the inferred haplotype data of 83 AIMs, we estimated the switch error rate as 1 per 22 SNPs in CEU, 1 per 25 SNPs in CHB, and 1 per 19 SNPs in UIG. In other words, on average there would be four potential phasing errors in CEU, three potential phasing errors in CHB, and four potential phasing errors in UIG. However, we think the switch errors have limited influence on the downstream analysis, i.e., the estimation of ancestral origin of chromosomal segments, because of the following reasons: (1) the recombination rate (breakpoints per cM) estimated from phased data is consistent with that estimated from unphased data; (2) considering the recombination rate, the frequency of breakpoints is much higher than that of switch errors—for example, the breakpoint rate in UIG is estimated at an average of 1.26 per 1 cM, or 85 breaks per 67.4 cM, whereas the switch error in UIG is only about 4 per 67.4 cM; (3) for many AIMs, we observed several UIG individuals with both alleles derived from the same ancestry; i.e., the phase information is not so important for those markers and individuals. Xu, Shuhua, et al. " Analysis of genomic admixture in Uyghur and its implication in mapping strategy." The American Journal of Human Genetics 82.4 (2008): 883-894.
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Post by Admin on Nov 27, 2018 20:11:58 GMT
Ethnic Uyghurs admixed or intermarried with Han Chinese only as recently as 2,500 years ago. Uyghurs have 60 per cent European ancestry and 40 per cent East Asian ancestry, formed by admixture between Tocharians from the west and Orkhon Uyghurs from the east in the 8th century AD. Ethnic Uyghurs are thought to be the descendants of the Tocharians, Indo-European peoples who inhabited in the Tarim Basin (modern Xinjiang, China) in ancient times. The Pazyryks from Mongolia and Altai cluster with Central and East Asian populations and have more East Eurasian mtDNA lineages (46.7%). Their common ancestors with haplogroup R1a1 lived from 20,000 ybp in south Siberia/northern China through 12,000 - 11,000 ybp in Hindustan and 6,900 ybp in north-western China. Apparently, the most ancient source of R1a1 haplotypes is provided by the people now living in northern China. Not later than 12,000 ybp, bearers of R1a1 were in the Hindustan, then went across Anatolia and the rest of Asia Minor between 10,000 and 9,000 ybp, and around 9,000 - 8,000 ybp, and then they arrived to the Balkans and spread over Europe (Klyosov 2012). The Uyghur population is genetically closer to European populations than Eastern Asian populations (60% European ancestry/40% East Asian ancestry) The Uyghur (UIG) population, settled in Xinjiang, China, is a population presenting a typical admixture of Eastern and Western anthropometric traits. UIG was formed by two-way admixture, with 60% European ancestry and 40% East Asian ancestry. Under the assumption of a hybrid isolation (HI) model, the admixture event of UIG occurred about 126 [107∼146] generations ago, or 2520 [2140∼2920] years ago assuming 20 years per generation. However, this result could be underestimated due to the assumption of a hybrid isolation (HI) model. In this model, Uyghur was formed by a single event of admixture during a short period of time, which might not be true of the real history of the Uyghur. Considering the geographical location where the Uyghur settled, continuous gene flow from populations of European and Asian descent was very likely (Xu et al. 2008). Prior to the emergence of nomadism and various forms of irrigation agriculture Xinjiang was lightly populated. Nomadic herders on the ground in Central Asia facilitated a gene flow between east and west Eurasia. With the development of new cultural technologies in western Eurasia, from the horse to the wheel, Xinjiang came to be settled by peoples from the west, which explains why 4,000 years ago blondes were relatively common in Xinjiang despite its Asian location. Around 2,000 years ago a reverse historical process occurred, the migration of Turkic peoples to the west from their Mongolian homeland. In some places the migration’s genetic impact was minimal; e.g., Turkey. But in Xinjiang, which is close to the original Turkic homeland, the cultural change was accompanied by a demographic shift as East Asian genes nearly approached parity with the west Eurasian genetic substrate. Figure 1 STRUCTURE Bar Views for K = 2–6 and Contour Plots for K = 2 and K = 6 The contour plots and genetic distance tree are color coded to correspond to the STRUCTURE plots. The significance levels for pairwise comparisons of clusters are given on the K = 6 contour plot (bottom) at the relevant borders. A fundamental problem with this estimate at K = 2 is the high improbability of the Uyghur population being admixed of two widely separated populations such as Europeans and eastern East Asians. Therefore, we also tested for additional subdivisions with STRUCTURE to see which populations were more closely related to Uyghurs. We observed that Central Asian populations including Uyghurs, Kazakhs, and Khanty did not form their own cluster until K = 6, indicating that the Central Asian cluster was not a completely distinct population group. From K = 3 to K = 5, the western part of East Asia (Kham, Baima, Qiang, Mongol) was distinguished from the eastern part of East Asia (Japanese, Korean, Hakka, Minnamese, Cantonese). Examining the “admixture” pattern of Uyghurs, it is clear that the proportion of western East Asia is much higher than that of eastern East Asia, especially when K = 5 (0.418 versus 0.128, respectively). Moreover, the South Asians and West Asians also contributed more than the Europeans to Uyghurs (0.180 versus 0.100, respectively). Including the western East Asians, South Asians, and West Asians when estimating the admixture rate of Uyghurs illustrates the difficulty with the concept of admixture for such intermediate populations—the estimate depends on the populations hypothesized to be admixed in the target population. Considering only the Europeans and the eastern East Asians may seem to indicate equal “contributions” to Uyghurs, which was the case in the study of Xu and Jin. In addition, our study showed that Central Asia clearly formed a cluster with significant borders when K = 6. The border of the Central Asian cluster went along Lake Baikal, the A-erh-chin Mountains, the Kunlun Mountains, the Hindu Kush, the Caspian Sea, and the Ural Mountains, matching the traditional anthropological definition of Central Asia. We performed pairwise t tests for the six clusters to estimate the significance of the borders (p values are marked on the map at bottom in Figure 1). The only insignificant gap around the Central Asian cluster was in northern Siberia, where people led a nomadic hunting lifestyle. Another insignificant border was the southern border of the western East Asian cluster, where people also led a nomadic hunting lifestyle. That area is believed to have been a migration pathway into East Asia for early modern humans.10,11 Such a nomadic hunting lifestyle might have been the easiest way to blur borders arising among populations through admixture during more recent human history. Though nomadic lifestyles may have blurred distinctions, those nonsignificant cluster comparisons might also simply be due to a lack of power for this specific set of SNPs to distinguish differences. Other borders among all pairs of the six clusters were significantly distinct. It is reasonable that the Caucasus, the Anatolian plateau, and the Himalayas became the borders of the clusters by minimizing gene flow and allowing allele frequency differences to accumulate by drift. Our analyses significantly divided East Asia into eastern and western parts, agreeing with the hypothesis that early modern humans entered East Asia in the south along two routes, the western route from Myanmar to Yunnan and the eastern route from Vietnam to Guangdong.10,12,13 The descendants of the migrants along these two routes would have accumulated significant genetic differences and subsequently would have had different effects on the gene pool of Uyghurs. Here we have demonstrated that the western East Asians are more closely related to Uyghurs than the eastern East Asians. To confirm the relative genetic affinity between Uyghurs and the other Eurasian populations, we performed principal component analysis (PCA) with SPSS 13.0. The results of principal components 1 versus 2 are plotted in Figure 2. It is obvious that two clusters exist: a European-West Asian and a far East Asian. The South Asian and Central Asian populations are scattered between the clusters of Europeans and East Asians. Notably, Uyghurs are much closer to the East Asians than to the Europeans. The clinal pattern seen in the PCA is also suggested by the sequential subdividing of the groups of populations in the series of increasing K for the STRUCTURE analyses. The first two PCA components account for just over 80% of the total variance, probably because some of the SNPs have very large allele frequency differences between Europe and far East Asia (Table S1). Figure 2 Principal Component Plot of Eurasian Populations Just over 80% of the variance among these populations based on the 68 SNPs in this study can be explained by the first two components. STRUCTURE cannot distinguish recent admixture from a cline of other origin, and these analyses cannot prove admixture in the Uyghurs; however, historical records indicate that the present Uyghurs were formed by admixture between Tocharians from the west and Orkhon Uyghurs (Wugusi-Huihu, according to present Chinese pronunciation) from the east in the 8th century CE.14 The Uyghur Empire was originally located in Mongolia and conquered the Tocharian tribes in Xinjiang. Tocharians such as Kroran have been shown by archaeological findings to appear phenotypically similar to northern Europeans,15 whereas the Orkhon Uyghur people were clearly Mongolians. The two groups of people subsequently mixed in Xinjiang to become one population, the present Uyghurs. We do not know the genetic constitution of the Tocharians, but if they were similar to western Siberians, such as the Khanty, admixture would already be biased toward similarity with East Asian populations. In conclusion, we argue that the Uyghurs' genetic structure is more similar to East Asians than to Europeans, in contrast to the reports by Xu and Jin, whose work may have been affected by their sparse population coverage. The median line of the Eurasian genetic landscape appears to lie to the west of the Xinjiang Uyghur Autonomous Region of China. When we have collected more data on these 34 populations, we should be able to refine these estimates. Am J Hum Genet. 2009 Dec 11; 85(6): 934–937.
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Post by Admin on Nov 29, 2018 19:38:24 GMT
Uyghurs live primarily in Xinjiang, a province in the far western region of China and crossed by the Silk Road which is an important pathway connecting Eastern Asia with Central Asia and Europe. As a result, Uyghurs have experienced extensive interaction with other Asian and European populations. Modern Uyghurs present an admixture of Eastern and Western anthropological and genetic traits1,2,3. To shed light on the historical interactions of the Uyghurs with the Europeans and Eastern Asians, a high-resolution genetic dataset as well as detailed population genetics and phylogenetic analyses based on the dataset are needed. Such a high-resolution dataset is also potentially useful in forensic applications either within Uyghur populations or to infer ancestry of DNA donors. Y chromosome contains the largest non-recombining block in human genome and can be used to trace the male line of descent4. Short tandem repeats (STRs) are genetic markers that are more informative than single nucleotide polymorphisms (SNPs) and reveal more recent events in population history, because of its high mutability and high degree of allelic polymorphism. A number of highly polymorphic Y chromosome STRs (Y-STRs) systems are useful and available for studies in population genetics and forensic sciences such as patrilineal relationship evaluation, mixture identification and ancestry inference5,6,7,8,9. Such Y-STRs systems have been successfully applied to Uyghur populations10,11,12,13. Figure 1: Geographic distribution of populations used in this study. Genetic relationship between the Uyghur population and reference populations in Eastern Asia or Europe The detailed typing results at the 26 Y-STR loci of 100 male individuals of Uyghur from southern Xinjiang are shown in Supplementary Table S1. Uyghur is known to be an admixture of Eastern Asian and European populations19. Using the high-resolution Y-STR loci system, we studied the genetic relationship of Uyghur and different Asian or European populations (Table 1) based on RST (Table 2), and MDS was used to visualize the results (Fig. 2A). To avoid using populations exclusively from the Eastern or Western extremes of Eurasia continent, we also included samples from Kazakhstan and Afghanistan that are in Central Asia. As is shown by the MDS plot (Supplementary Figure S1), the Uyghur population lies between the Eastern Asian and European populations. Our results are consistent with the hypothesis that both Eastern Asian and European populations contributed to the current gene pool of the Uyghur population. Uyghur populations are also genetically close to Central Asian populations, reflecting the communications among the populations due to geographic proximity, silk roads and the genetic contribution of the Mongols suggested by previous studies20,21,22,23. On the other hand, Central Asian populations are also closely related to Eastern Asian and European populations, consistent with previous studies suggesting the admixed nature of Central Asia21,22,23,24,25. The two observations collectively substantiate the inference that Eastern and Western Eurasian populations are genetic donors of Uyghur and its closely related Central Asian populations.
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Post by Admin on Dec 1, 2018 18:05:37 GMT
However, because the only Y-STR data available for Central Asian populations are based on 17 Y-STR loci, there is a higher chance to infer biased genetic distances based on the available data compared to using a dataset based on 23 Y-STR loci typed using the PowerPlex Y23 kit. Such bias may explain the unexpectedly long genetic distance from Han populations to the rest of the populations, and the clustering of several geographically and genetically isolated minorities in southern and northern China (Supplementary Figure S1). Among the 19 reference populations from Europe and Eastern Asia where information on 23 Y-STR loci is available, Hui is the most closely related to Uyghur ( RST = 0.0132) and Dai is the most distantly related to Uyghur ( RST = 0.1717). The AMOVA results also show that the Uyghur population is slightly more closely related to the European populations than the Eastern Asian populations (p = 0.074), which is consistent with the studies of Xu et al. using SNP markers19, Zhao et al. using classical markers25 and Comas et al. using mtDNAs26. However, the observed genetic relationships could be complicated by many factors including the geographic origins of the samples, the choice of genetic markers and the coverage of reference populations27. A number of other studies suggest that Uyghur is more closely related to Eastern Asian populations than European populations27,28,29. One possible cause of the discrepancy is the difference in the geographic locations of the Uyghur populations that are analyzed in different studies. The Uyghur populations described in the present study and in the study of Xu et al. are in southern Xinjiang, which are less affected by the recent migrations of Han Chinese30,31. Figure 2: MDS plot and neighbour-joining phylogenetic tree. Evolutionary relationships between the Uyghur population and the Asian and European populations are inferred from the Neighbor-joining tree based on the RST values (Fig. 2B). It has been shown that, in neighbor-joining trees, an admixed population will always lie on the path between the source populations32. Indeed, the Uyghur population lies between the European populations and the Eastern Asian populations. The distance-based phylogeny is strongly supportive of the admixed nature of the Uyghur population and the Central Asian populations. Similar to the MDS plot, when the profile is reduced to 17 Y-STR loci, the phylogeny exhibited unexpected topologies or branch lengths among the reference populations potentially due to the bias of using less Y-STR markers. Among the Eastern Asian and European populations, the Uyghur population has a closer relationship with the Hui (Cangzhou, China), the Hungarian and the Mongolian populations. The proximity between the Uyghur population and the Hui population is consistent with historical records, which indicate that the present Hui population is an admixture of Central Asian, Han, Mongolian, Uyghur and other populations formed around the 13th century. The relatively close relationship between the Uyghur population and the Hungarian population is consistent with the Asian origin hypothesis of Hungarians33,34,35,36,37. The proximity between the Uyghur population and the Mongolian population could be speculatively explained by the migration of Orkhon Uyghurs, proposed ancestors of present Uyghurs, from Mongolia to Xinjiang around the 9th century. The migration allows gene flow between the Orkhon Uyghurs and the indigenes in Xinjiang, such as Tocharians, that are genetically similar to northern Europeans28,38,39. The fact that the indigenous population is much larger than the Orkhon Uyghur population may also explain why the Uyghur is genetically closer to European populations than Eastern Asian populations as is shown in this study. The ability of the Y-STR loci to infer ancestry of DNA donors Ancestry informative DNA markers are valuable tools in forensic sciences. For Uyghur samples, ancestry inference could be especially challenging due to the admixed nature of the population. We investigated the power of the Y-STR system in ancestry inference by asking how well it can discriminate Uyghur samples from different Asian and European samples. The Y-DNA haplogroup tree involving individual samples from Uyghur and reference populations revealed no clear separation of the Uyghur samples from the reference samples (Fig. 3). The Uyghur samples exhibited one primary haplogroup M429 containing 84 samples (out of 95 Uyghur samples used for the analysis) mixed with samples from mainly Eastern Asia and Europe, with the rest of the samples distributed in haplogroups M89 and M2. It is worthwhile to note that the relative abundance of Uyghur, Eastern Asian, Central Asian and European samples in each haplogroup also depends on the total number of samples used in the study that are from Uyghur, Eastern Asia, Central Asia and Europe.
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Post by Admin on Dec 2, 2018 18:16:16 GMT
Figure 3: Y-DNA haplogroup tree of Uyghur, European, Central Asian and Eastern Asian samples. LDA was performed on the Uyghur, European, Central Asian and Eastern Asian samples to look for markers that are ancestry-informative. Figure 4A shows all individual samples plotted on the two LDA factors (axes F1 and F2). The first factor (F1) explained the majority (95.807%) of the variation. The markers DYS635 and DYS438 had the largest correlation coefficient (0.731 and 0.5) with the first and second factor, respectively (Fig. 4B). The plot showed no obvious separation of the Uyghur samples from the reference samples, although the Eastern Asian samples were well separated from the European samples. Due to the long history of admixture of Uyghurs, the present multiplex Y-STR data alone might be insufficient to discriminate Uyghur samples from European or Asian samples. A more comprehensive dataset that allows inclusion of more Y-STR loci may increase the power in finding ancestry-informative markers. Figure 4: LDA of Uyghur, European, Central Asian and Eastern Asian samples based on Y-STR genotypes. In this study we genotyped 100 Uyghur males at 26 Y-STR loci and demonstrated that the 26 Y-STR loci system is useful in describing genetic variation in a Uyghur population in southern Xinjiang. Forensic parameters of the 26 Y-STR loci system showed that the system has high discriminatory power within the Uyghur population and has potential application in forensic studies. We showed that the Uyghur population from southern Xinjiang is genetically admixed with reference populations in Eastern Asia and Europe, with a slightly closer relationship to the European populations. Due to the admixed nature of Uyghur, it is hard to differentiate Uyghur DNA donors from donors in Asia or Europe based on the available Y-STR information. Bian, Y. et al. Analysis of genetic admixture in Uyghur using the 26 Y-STR loci system. Sci. Rep.6, 19998 (2016).
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