An updated tree of Y-chromosome Haplogroup O and revised phylogenetic positions of mutations P164 and PK4

Y-chromosome Haplogroup O is the dominant lineage of East Asians, comprising more than a quarter of all males on the world; however, its internal phylogeny remains insufficiently investigated. In this study, we determined the phylogenetic position of recently defined markers (L127, KL1, KL2, P164, and PK4) in the background of Haplogroup O. In the revised tree, subgroup O3a-M324 is divided into two main subclades, O3a1-L127 and O3a2-P201, covering about 20 and 35% of Han Chinese people, respectively. The marker P164 is corrected from a downstream site of M7 to upstream of M134 and parallel to M7 and M159. The marker PK4 is also relocated from downstream of M88 to upstream of M95, separating the former O2(*) into two parts. This revision evidently improved the resolving power of Y-chromosome phylogeny in East Asia.     

Differential Y-chromosome Anatolian Influences on the Greek and Cretan Neolithic

The earliest Neolithic sites of Europe are located in Crete and mainland Greece. A debate persists concerning whether these farmers originated in neighboring Anatolia and the role of maritime colonization. To address these issues 171 samples were collected from areas near three known early Neolithic settlements in Greece together with 193 samples from Crete. An analysis of Y-chromosome haplogroups determined that the samples from the Greek Neolithic sites showed strong affinity to Balkan data, while Crete shows affinity with central/Mediterranean Anatolia. Haplogroup J2b-M12 was frequent in Thessaly and Greek Macedonia while haplogroup J2a-M410 was scarce. Alternatively, Crete, like Anatolia showed a high frequency of J2a-M410 and a low frequency of J2b-M12. This dichotomy parallels archaeobotanical evidence, specifically that while bread wheat ( Triticum aestivum ) is known from Neolithic Anatolia, Crete and southern Italy; it is absent from earliest Neolithic Greece. The expansion time of YSTR variation for haplogroup E3b1a2-V13, in the Peloponnese was consistent with an indigenous Mesolithic presence. In turn, two distinctive haplogroups, J2a1h-M319 and J2a1b1-M92, have demographic properties consistent with Bronze Age expansions in Crete, arguably from NW/W Anatolia and Syro-Palestine, while a later mainland (Mycenaean) contribution to Crete is indicated by relative frequencies of V13.     

A Perspective on the History of the Iberian Gypsies Provided by Phylogeographic Analysis of Y-Chromosome Lineages

The European Gypsies, commonly referred to as Roma, are represented by a vast number of groups spread across many countries. Although sharing a common origin, the Gypsy groups are highly heterogeneous as a consequence of genetic drift and different levels of admixture with surrounding populations. With this study we aimed at contributing to the knowledge of the Roma history by studying 17 Y-STR and 34 Y-SNP loci in a sample of 126 Portuguese Gypsies. Distinct genetic hallmarks of their past and migration route were detected, namely: an ancestral component, shared by all Roma groups, that reflects their origin in India (H1a-M82; ∼17%); an influence from their long permanence in the Balkans/Middle-East region (J2a1b-M67, J2a1b1-M92, I-M170, Q-M242; ∼31%); traces of contacts with European populations preceding the entrance in the Iberian Peninsula (R1b1c-M269, J2b1a-M241; ∼10%); and a high proportion of admixture with the non-Gypsy population from Iberia (R1b1c-M269, R1-M173/del.M269, J2a-M410, I1b1b-M26, E3b1b-M81; ∼37%). Among the Portuguese Gypsies the proportion of introgression from host populations is higher than observed in other groups, a fact which is somewhat unexpected since the arrival of the Roma to Portugal is documented to be more recent than in Central or East Europe.     

傣族、水族和仡佬族人群的α地中海贫血基因突变分析

目的研究傣族、水族和仡佬族人群中常见α地中海贫血基因突变的频率和分布,探讨我国南方少数民族中α地中海贫血的分子流行病学特点。方法AK483例云南省傣族、180例贵州省水族和177例贵州省仡佬族的外周静脉血样本中分离基因组DNA,采用单管多重缺口PCR（Gap-PCR）,进行-α^3.7、-α^4.2和-^SEA三种缺失型α地中海贫血基因突变的检测。结果被检测的傣族、水族和仡佬族样本中α地中海贫血基因突变的携带率分别为34．16％、12．22％和5．08％,以云南傣族的携带率最高。-α^3.7、-α^4.2和--^SHA突变的等位基因频率在傣族中分别是14．18％、0．31％和4．14％,在水族中分别是2．50％、0．28％和3．33％,在仡佬族中分别是1.41％、0．56％和0．56％。-α^3.7是傣族中最常见的突变类型,--^SEA则是水族中的常见突变类型。结论云南傣族、贵州水族和仡佬族中有较高的α地中海贫血基因突变携带率,我国南方不同地区和民族之间在基因突变的频率和分布上均有明显差异。     

云南省傣族、汉族人群乙型肝炎病毒感染与IL-6-572C/G和IFNAR1-168G/C的关联性研究

目的:探讨云南省西双版纳地区傣族和汉族人群IL-6-572C/G和I型干扰素受体1(interferon alpha receptor 1,IFNAR1)-168G/C位点单核苷酸多态性与乙型肝炎病毒(HBV)感染后疾病转归的关联性。方法:采集西双版纳州傣族、汉族人群血液样本共600份,其中每个民族包括健康对照组100名、HBV感染患者200名(含100名自限性恢复患者和100名慢性乙肝患者),运用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)和DNA测序技术对IL-6-572C/G和IFNAR1-168G/C位点进行基因分型。结果:傣族人群中,-572C/G位点基因型多态性与HBV感染后转归的关联性并无统计学显著性。C、G等位基因型在HBV感染组、正常对照组之间和慢性乙肝组、自限恢复组之间差异无统计学显著性。但是在G显性模式(GG+CG/CC)下,GG+CG基因型为HBV感染者发展成为慢性乙型肝炎患者的保护因素(P0.05)。汉族人群中,-572C/G位点基因型和等位基因分布频率在各组比较中无统计学显著性,并且在G显性模式和G隐性模式比较中也无统计学显著性。在上述4种比较中,IFNAR1-168G/C位点在汉族和傣族样本中的差异均无统计学显著性。结论:IL-6-572C/G位点GG+CG基因型可能是傣族人群中HBV感染者发展成为慢性乙型肝炎的保护因素,而IFNAR1-168G/C多态性与HBV感染后转归在傣、汉两族中并无显著性关联。     

Mitochondrial DNA polymorphisms in Yunnan nationalities in China

Nucleotide sequences of the D-loop region of human mitochondrial DNA from four Yunnan nationalities, Dai, Wa, Lahu, and Tibetan, were analyzed. Based on a comparison of 563-bp sequences in 99 people, 66 different sequence types were observed. Of these, 64 were unique to their respective populations, whereas only 2 types were shared between the Lahu and Wa nationalities. The D-loop sequence variation and phylogenetic analysis suggested that the 99 mtDNA lineages were classified into eight clusters in the phylogenetic tree. All lineages that had a 9-bp deletion in the COII/tRNA^Lys intergenic region appeared in one cluster in the D-loop tree, suggesting a single event of the deletion in the Yunnan nationalities studied. Genetic distances, based on net nucleotide diversities between populations including Han Chinese and mainland Japanese, revealed that the Dai, Wa, Lahu, and Han Chinese are closely related to each other, while Tibetan and mainland Japanese formed a single cluster. The bootstrap probabil-ity of separation between the Dai-Wa-Lahu-Chinese clade and the Tibetan-Japanese clade was 99%, indicating that there are at least two different origins among minority groups in Yunnan province. Although the genetic distance between Tibetan and Japanese within the clade is rather long, the results may shed light on the origins of mainland Japanese. Received: December 22, 2000 / Accepted: January 18, 2001     

Phylogeographic analysis of mtDNA variation in four ethnic populations from Yunnan Province: new data and a reappraisal

 Two sets of mitochondrial DNA (mtDNA) hypervariable segment I (HVS-I) data from four ethnic populations (Tibetan, Va, Dai, and Lahu) from Yunnan Province, China, were analyzed here by using phylogeographic methods. The results suggest that more attention should be paid to sampling methodology when addressing the genetic relationship and affinity among ethnic populations. Comparison of related data from different labs may serve as a check for the credibility of the data and will help discern the origin of the ethnic populations. Generally, Tibetan populations have more north-prevalent haplogroups (clades of the mtDNA phylogeny), while Dai and Lahu populations have high frequencies of south-prevalent haplogroups. The Vas, although autochthonous according to historical records, show signs of gene admixtures from northern and southern populations, for they harbor high frequencies of the south-prevalent haplogroup F and the north-prevalent haplogroup D as well as other northern mtDNA lineages such as M9 and G2a. The consanguineous marriage customs of the Lahu, together with possible genetic drift during this group's historical migration, left a conspicuous genetic imprint on its current gene pool. Received: February 8, 2002 / Accepted: March 7, 2002     

The phylogenetic and geographic structure of Y-chromosome haplogroup R1a

R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25 000 (95% CI: 21 300–29 000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800–6800) years. The spatial frequency distributions of R1a sub-haplogroups conclusively indicate two major groups, one found primarily in Europe and the other confined to Central and South Asia. Beyond the major European versus Asian dichotomy, we describe several younger sub-haplogroups. Based on spatial distributions and diversity patterns within the R1a-M420 clade, particularly rare basal branches detected primarily within Iran and eastern Turkey, we conclude that the initial episodes of haplogroup R1a diversification likely occurred in the vicinity of present-day Iran.     

Ancient links between Siberians and Native Americans revealed by subtyping the Y chromosome haplogroup Q1a

To investigate the structure of Y chromosome haplogroups R-M207 and Q-M242 in human populations of North Asia, we have performed high-resolution genotyping using both single nucleotide polymorphisms and short tandem repeat (STR)-based approaches of 121 M207- and M242-derived samples from 885 males of 16 ethnic groups of Siberia and East Asia. As a result, the following Y chromosome haplogroups were revealed: R1b1b1-M73 (2.0%), R1b1b2-M269 (0.7%), R2-M124 (1.1%), Q1a*-MEH2 (0.5%), Q1a2-M25 (0.1%), Q1a3*-M346 (9.2%) and Q1a3a-M3 (0.2%). Despite the low coalescence age of haplogroup Q1a3*-M346, which is estimated in South Siberia as about 4.5±1.5 thousand years ago (Ka), divergence time between these Q1a3*-M346 haplotypes and Amerindian-specific haplogroup Q1a3a-M3 is equal to 13.8±3.9?Ka, pointing to a relatively recent entry date to America. In addition, unique cluster of haplotypes belonging to Q1a*-MEH2 was found in Koryaks inhabiting the Sea of Okhotsk coast (at a frequency of 10.3%). Although the level of STR diversity associated with Q1a*-MEH2 is very low, this lineage appears to be closest to the extinct Palaeo-Eskimo individuals belonging to the Saqqaq culture arisen in the New World Arctic about 5.5?Ka. This finding suggests that Q1a*-MEH2 likely traces a population migration originating in Northeast Siberia across the Bering Strait.     

云南新平地区傣族学龄前儿童β-地中海贫血基因突变类型分析

目的探讨云南新平傣族学龄前儿童β-地中海贫血的基因突变类型及其基因型频率特征。方法对407名傣族学龄前儿童进行血细胞分析,以平均红细胞体积(MCV)<80fl或平均血红蛋白量(MCH)<27pg为血液学表型初筛阳性样本进行血红蛋白电泳,HbA2>3.5%或HbF>2%为血红蛋白表型阳性样本进行14种东南亚常见基因分析。结果在407人中血液学筛查出235例进行血红蛋白电泳阳性60例在进行基因诊断分析,有21例得到确诊用检出5种突变基因,包括7种基因型常见的突变位点为41-42M(杂),基因型频率为47.62%;其余基因突变位点及其频率为:β-EM(14.29%),17M(9.52%),41-42M(纯)(9.52%),654M(杂)(9.52%),17/71-72M(双重杂)(4.76%),17/β-EM(双重杂)(4.76%)。结论初步探明了该地区学龄前儿童β-地中海贫血基因突变类型及基因型频率,获取其分子生物流行病学资料,为今后对该地人群进行疾病的防治、优生优育、遗传咨询、提高人口素质具有重要的指导意义。     

三个群体MICA基因外显子2、3和4的多态性研究

目的 调查上海地区汉族、云南傣族和新疆维吾尔族3个群体MICA基因外显子2、3和4的多态性。方法 采用聚合酶链反应－序列特异的寡核苷酸探针杂交（polymerase chain reaction and sequence-specific oligonucleotide robing,PCR-SSOP）方法，分析183名汉族、41名傣族和66名维吾尔族正常人群的MICA胞外区等位基因多态性。结果 分别在汉族、傣族和维吾尔族中检测出10、7和9个MICA等位，其中MICA^*008在汉族和维吾尔族中频率最高，而傣族中MICA^*010的频率最高。3个民族MICA等位基因分布方式各不相同，而且维吾尔族的等位基因分布与另外两个民族相比，差异具有显著性。结论 MICA等位基因分布方式具有民族地区特异性。     

云南省四个少数民族中所见的G6PD基因突变型

目的 通过鉴定云南省白族、傣族等少数民族中的Ｇ６ＰＤ基因突变型,统计大理市白族Ｇ６ＰＤ缺乏症发生率及基因频率,以了解分子进化和民族起源,并为Ｇ６ＰＤ缺乏症的防治提供理论依据。方法 用错配碱基ＰＣＲ／ＲＥ、ＰＣＲ－ＳＳＣＰ、ＡＲＭＳ法和ＤＮＡ序列分析等检测Ｇ６ＰＤ基因点突变。结果 经ＤＮＡ序列分析确认,首次在白族人群中发现Ｇ６ＰＤ Ｇ１３８８Ａ,发生率４２％、Ｇ１３７６Ｔ发生率２１％、Ａ９５Ｇ发生率     

Analysis of HLA class II allogenotyping in Australian Aborigines and Papua New Guinea populations

Human leukocyte antigen (HLA) class II allogenotyping has been applied to investigate the polymorphism of the DRB, DQB1, DQB2, DQA1, and DQA2 genes in Aborigines from the East Coast of Australia and in Melanesians from the Papua New Guinea North-East Coast and Highlands. Three new DR/DQ arrangements were observed, DRw14/DQB1-2b/DQA1-1a and DRw5Nauru/DQB1-3a/DQA1-2 (n Australian Aborigines), and DRw5Nauru/DQB1-1a/DQA1-1b (in Madang). DQA2 and DQB2 allogenotyping with TaqI and PstI digested genomic DNA revealed little polymorphism among the Papua New Guineans, with DQA2-Xa1 and DQB2-Xb1 the most common alleles in all the groups. However, the presence of DQA2-Xa2 in Papuans and Australian Aborigines reflects the degree of admixture with Caucasoids while the DQA2-Xa4 allele in Madang is probably a marker of Mongoloid origin.     

Isolates in a corridor of migrations: a high-resolution analysis of Y-chromosome variation in Jordan

A high-resolution, Y-chromosome analysis using 46 binary markers has been carried out in two Jordan populations, one from the metropolitan area of Amman and the other from the Dead Sea, an area geographically isolated. Comparisons with neighboring populations showed that whereas the sample from Amman did not significantly differ from their Levantine neighbors, the Dead Sea sample clearly behaved as a genetic outlier in the region. Its high R1*-M173 frequency (40%) has until now only been found in northern Cameroonian samples. This contrasts with the comparatively low presence of J representatives (9%), which is the modal clade in Middle Eastern populations, including Amman. The Dead Sea sample also showed a high presence of E3b3a-M34 lineages (31%), which is only comparable to that found in Ethiopians. Although ancient and recent ties with sub-Saharan and eastern Africans cannot be discarded, it seems that isolation, strong drift, and/or founder effects are responsible for the anomalous Y-chromosome pool of this population. These results demonstrate that, at a fine scale, the smooth, continental clines detected for several Y-chromosome markers are often disrupted by genetically divergent populations.     

Distribution of HLA-A,HLA-B,HLA-C,and HLA-DRB1 alleles and haplotypes in Jingpo minority in Yunnan province of China

HLA-A, HLA-B, HLA-C, and HLA-DRB1 allele frequencies and estimated haplotype frequencies from 105 unrelated healthy Jingpo ethnic subjects who living in Dehong Dai-Jingpo Autonomous Prefectures, Yunnan Province, southwest China has been reported. HLA genes were genotyped by SSOP typing method using Luminex Multi-Analyte Profiling system. Jingpo ethnic nationality belongs to southern group of East Asians, but with its specific HLA alleles and haplotypes characteristic.     

Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality,China

PurposeThalassemia is one of the most common monogenic diseases in southwestern China, especially among the Dai ethnic group. Here, we explore the feasibility of a next-generation sequencing (NGS) screening method specifically for the Dai people.MethodsBlood samples were obtained from Dai people for premarital screening. Double-blind, parallel hemoglobinopathy screening was conducted using both traditional hematological methods (red cell indexes and hemoglobin electrophoresis, then DNA sequencing) and an NGS approach.ResultsAmong 951 tested individuals, we found a thalassemia carrier rate of 49.5% (471/951) using the NGS screen, in contrast to 22.0% (209/951) found using traditional methods. Almost 74.8% (217/290) of α-thalassemia carriers and 30.5% (25/82) of composite α- and β-thalassemia carriers were missed by traditional screens. The proportion of such α- and β-thalassemia carriers among the Dai people is 8.6% (82/951). For β-thalassemia carriers, the high ratio (66/99) of CD26 mutations may suggest a correlation between CD26 and the environmental adaption of the Dai people.ConclusionsMethodological comparisons demonstrate the superiority of NGS for both sensitivity and specificity, provide a comprehensive assessment of thalassemia screening strategies, and indicate that NGS is a competitive screening method, especially among populations with a high prevalence of disease.Genet Med advance online publication 26 January 2017     

Genomic diversity of natural killer cell receptor genes in three populations

We report the distribution of genes encoding 11 killer cell immunoglobulin-like receptors (KIR) and 2 CD94:NKG2 receptors, in 32 Caucasians, 67 Australian Aborigines and 59 Vietnamese. The inhibitory and the activating KIR genes were found at different frequency in the three populations. No correlation was found between the polymorphism of the KIR genes and the HLA specificities of the tested samples. The most significant KIR associations were 2DL2 with 2DS2; 2DL2 with 2DS3 and 3DL1 with 2DS4 in all three study groups. In Caucasians and Vietnamese 2DS2 was associated with 2DS3 and 2DS1with 3DS1. KIR 2DL1 was strongly associated with three other KIRs: 2DL3, 3DL1 and 2DS4 in Aborigines. The distribution of the KIR phenotypes was different in the three populations. The AA1 phenotype was frequent in Vietnamese (42.4%) and Caucasians (31.2%), but very rare in Aborigines (1.5%). In contrast, the BB7 phenotype was very common for Aborigines (22.4%) and was absent in the two other groups. Our data demonstrate that different associations and putative KIR haplotypes could be distinguished in different populations.     

Distribution of HLA gene and haplotype frequencies in Taiwan: a comparative study among Min-nan, Hakka, Aborigines and Mainland Chinese

A total of 8,497 blood samples were typed for HLA-A, B, DR and DQ. Of these, 7,137 Min-nan, 714 Hakka, 535 Mainland Chinese (152 from North China, 211 from Middle China, and 172 from South China) and 111 Aborigines were randomly selected from Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). Differences in HLA gene and antigen frequencies have been observed between various ethnic groups of the Chinese population in Taiwan. The phylogenic tree shows Taiwan Aborigines and Javanese cluster together; Min-nan shares a common cluster with Hakka, Southern Hans and Thai; and Northern Hans shares a cluster with Middle Hans. The separation between Northern/Middle and Southern Chinese Hans support the idea that Northern and Southern Chinese have different genetic background. Aborigines appeared to be quite distinct in the distribution of a majority of the class I and class II antigens. High frequency of HLA-A24 (60.4%) and relatively restricted HLA polymorphisms are noted in Aborigines. The HLA haplotypes with high frequency in Aborigines included A24-B60-DRB1*04, A24-B60-DRB1*14, A24-B48-DRB1*04, and A24-B48-DRB1*14, which are different from the other ethnic groups. Although the phylogenic tree separates Aborigines and Han Chinese populations, 4 out of 20 most common HLA-A, -B, and -DR haplotypes presented in both Aborigines and Han Chinese may reflect an ancient common origin or intermixture between early settlers of Han Chinese and Taiwan Aborigines. The results in this study are essentially a summary of the observed gene/haplotype frequencies and differences among various ethnic groups in Taiwan.     

Towards understanding the origin and dispersal of Austronesians in the Solomon Sea: HLA class II polymorphism in eight distinct populations of Asia-Oceania.

HLA class II nucleotide sequence polymorphisms were examined in eight ethnic groups of Asia-Oceania using DNA typing methods. Allele frequencies and characteristic DR/DQ haplotypes were determined and compared with those of other populations of Asia-Oceania. Genetic distances were measured to show the genetic relationship within the studied populations as well as between the studied populations and previously published populations. Phylogenetic trees were constructed based on HLA allele frequencies using the neighbour-joining method. The populations, mainly Trobriand Islanders, Roro, Tolai, Western Samoans and Taiwanese Aborigines, are characterized by a reduced diversity at the HLA loci examined, especially for DPB1. The high frequency of the 'Asian'-specific DPB1*0501 allele in Trobrianders and Roro, but also in Western Samoans and Taiwanese Aborigines, was the most striking result. The prevalence of DPB1*0501 and the short genetic distance from Trobriander and Roro to Taiwanese Aborigines provide evidence that the origin of the Austronesian odyssey is south-east Asia, and Taiwan could be an important part of it. The relatedness of Trobrianders to the Polynesian population from Western Samoa indicates a probable recent common ancestor. The observed lack of diversity may reflect bottleneck(s) and/or limited diversity of the founding population. Analysis of HLA class I antigens, together with mt-DNA and Y-chromosomal studies, will give us further information about the settlement of the Trobriand and other islands during the colonization of the Pacific.     

Phylogeography of Y-chromosome haplogroup Q1a1a-M120, a paternal lineage connecting populations in Siberia and East Asia

Background: Previous studies have suggested that the human Y-chromosome haplogroup Q1a1a-M120, a widespread paternal lineage in East Asian populations, originated in South Siberia. However, much uncertainty remains regarding the origin, diversification, and expansion of this paternal lineage.

Aim: To explore the origin and diffusion of paternal Q-M120 lineages in East Asia.

Subjects and methods: The authors generated 26 new Y chromosome sequences of Q-M120 males and co-analysed 45 Y chromosome sequences of this haplogroup. A highly-revised phylogenetic tree of haplogroup Q-M120 with age estimates was reconstructed. Additionally, a comprehensive phylogeographic analysis of this lineage was performed including 15,007 samples from 440 populations in eastern Eurasia.

Results: An ancient connection of this lineage with populations in Siberia was revealed. However, this paternal lineage experienced an in-situ expansion between 5000 and 3000?years ago in northwestern China. Ancient populations with high frequencies of Q-M120 were involved in the formation of ancient Huaxia populations before 2000?years ago; this haplogroup eventually became one of the founding paternal lineages of modern Han populations.

Conclusion: This study provides a clear pattern of the origin and diffusion process of haplogroup Q1a1a-M120, as well as the role of this paternal lineage during the formation of ancient Huaxia populations and modern Han populations.