新疆维吾尔族、哈萨克族人群HLA-DQA1、-DQB1两基因座多态性的研究及与25个种族或民族的比较分析

应用ＰＣＲ－ＲＦＬＰ基因分型技术,首次对我国新疆地区维吾尔族和哈萨克族２个少数民族群体的ＨＬＡ－ＤＱＡ１、－ＤＱＢ１两个基因座的多态性进行了研究。结果显示,在ＤＱＡ１８个等位基因中,维族和哈族均表现为ＤＱＡ１＊０３０１最常见。最少见的ＤＱＡ１等位基因,在维族中为ＤＱＡ１＊０４０１和＊０６０１,而在哈族中为ＤＱＡ１＊０６０１;在ＤＱＢ１１６个等位基因中,ＤＱＢ１＊０２０１和＊０３０１在维族和哈族中均表现为最常见。在维族中未观察到ＤＱＢ１＊０５０２、＊０５０３２和＊０５０４,在哈族中未观察到ＤＱＢ１＊０５０３２、＊０５０４和＊０６０５等位基因。统计分析表明,维族和哈族ＤＱＡ１、ＤＱＢ１各等位基因的分布无显著性差异,说明维、哈族间具有较密切的亲缘关系。在以２７个种族或民族的ＨＬＡ－ＤＱＡ１、－ＤＱＢ１两基因座基因频率构建的分子系统树上,维族和哈族独立于其他群体而聚类,独处一支。维族和哈族接近蒙古人种,而离高加索人种较远。     

新疆维吾尔族,哈萨克族人群HLA—DQA1,—DQB1两基因座多态性的研究？…

应用ＰＣＲ－ＲＦＬＰ基因分型技术,首次对我国新疆地区维吾尔族和哈萨克族２个少数民族群体的ＨＬＡ－ＤＱＡ１,－ＤＱＢ１两个基因座的多态性进行了研究,结果显示,在ＤＱＡ１８个等位基因中,维族和哈族表现为ＤＱＡ１＊０３０１最常见,最少见的ＤＱＡ１等位基因,在维族中的ＤＱＡ１＊０４０１和０６０１,而在哈族中ＤＱＡ１＊０６０１;在ＤＱＢ１１６个等位基因中,ＤＱＢ１＊０２０１和＊０３０１在维族和哈族中均表现为     

新疆吐鲁番地区维吾尔族HLA-DQA1等位基因多态性研究

目的：探讨新疆吐鲁番地区维吾尔族HLA—DQA1等位基因多态性。方法：采用聚合酶链反应一序列特异性引物技术,检测107例新疆吐鲁番地区维吾尔族健康个体的HLA—DQA1等位基因频率,分析HLA—DQA1基因多态性,并将所得结果与国内其他民族的同类资料进行比较。结果：新疆吐鲁番地区维吾尔族健康个体中共检出10个等位基因,以DQA1＊0104（O．3727）、DQA1＊0501（0．2636）、DQA1＊0103（0．1318）的频率较高,DQA1＊0401（0．0045）、DQA1＊0601（0．0091）的频率较低。结果与国内其他民族的同类资料进行比较,等位基因分布频率上有共同点,也有一定的独特性。结论：新疆吐鲁番地区维吾尔族HLA—DQA1基因,与国内其他民族群体的资料比较,总体检验有显著差异（p〈0．01）,显示人类的遗传系统既有共性亦有各自的特点,显示华人群体遗传背景的复杂性,结果为人类学研究和HLA—DQA1基因相关的疾病提供了较为重要的信息.     

用ＰＣＲ—ＳＳＯ方法研究云南西部彝族ＨＬＡ—ＤＱＢ１基因的多态性

应用ＰＣＲ－ＳＳＯ基因分型技术,对我国云南西部地区３代内无血缘关系的７６个彝族健康个体进行了ＬＡ－ＤＱＢ１位点的基因分型。结果显示,在ＤＱＢ１的３８个等位基因中,观察到１３个等位基因,云南西彝族表现为ＤＱＢ１＊０３０１（３６．１８％－３６．８４％）最常见。其他频率大于５％的等位基因还有ＤＱＢ１＊０５０２（１０．５３％－１１．１８％）、ＤＱＢ１＊０４０１（９．２１％）、ＤＱＢ１＊０３０２（８．５５％－９．２１％）、ＤＱＢ１*0601(7．８９％）ＤＱＢ１＊０５０３１（６．５８％）、ＤＱＢ１＊０３０３２（５．９２％－６．５８％）。和其他１３个华人群体ＤＱＢ１等位基因的频率比较分析表明,总体上,云南西彝族和其他各华人群体间都存在很大的差异。显示其ＨＬＡ等位基因频率分布的民族独特性。     

福建畲族群体17个Y-STR基因座单倍型及遗传关系

应用Y-filerTM试剂盒及基因分型技术,检测152份福建畲族无关男性个体17个Y-STR基因座的多态性分布,计算等位基因频率及单倍型多样性,并结合已公开发表的其他11个群体相应基因座的单倍型资料,分析福建畲族群体遗传距离和聚类关系。福建畲族DYS385a/b基因座检出50种单倍型,其余15个Y-STR基因座分别检出3-11个等位基因,基因多样性GD值在0.4037(DYS391)～0.9725(DYS385a/b);观察到DYS19和DYS390基因座双等位基因和DYS385a/b基因座三等位基因,以及DYS448等部分基因座出现的"off-ladder"等位基因现象。17个Y-STR基因座共同构成的单倍型144种,其中138种单倍型出现1次,5种出现2次,1种出现4次,累计GD值为0.9990。从遗传距离分析发现,福建畲族与浙江汉族之间的遗传距离最近(0.0042),与青海藏族(0.2378)之间的遗传距离相对较远。福建畲族最靠近由台湾群体、浙江汉族、南方汉族等典型南方汉族群体聚成的分支区域。结果表明该17个Y-STR基因座在福建畲族群体中具有丰富的遗传多态性,对建立Y染色体STR数据库,研究群体遗传学和进行法医学应用有重要意义。     

青海藏族HLAⅡ类基因多态性的研究

用PCR－RFLP的技术进一步研究了青海藏族HLA－DPB1的多态性。在19个HLA－DPB1的等位基因中,共检出18个等位基因。其中,*0501的频率最高（AF＝380％）;其次为*0201（AF＝20．0％）;未检出*1601。在HLA－DPB1各等位基因的分布上,藏族与中国南方汉族、中国北方汉族等无明显差异,而与高加索人及尼格罗人的差异则较为显著。综合隶属于三大人种11个群体中的HLA－DQAl、－DQBl和一DPBl基因座各等位基因的分布频率,用UPGMA方法构建了分子系统树,实验结果进一步证实汉藏同源说。     

山西汉族17个Y-STR基因座遗传多态性及遗传关系

为了调查山西汉族群体17个Y-STR基因座的多态性分布,探讨其群体遗传学及法医学应用价值,文章应用Y-filer TM试剂盒检测222名山西汉族无关男性个体的17个Y-STR基因座,用ABI3130遗传分析仪进行基因分型,计算等位基因频率及单倍型多样性,并结合已公开发表的国内其他13个群体相关数据资料,分析山西汉族群体遗传距离和聚类关系。结果:山西汉族个体中共检出219种单倍型,单倍型多样性为0.9999;基因多样性GD值在0.3894(DYS391)~0.9755(DYS385a/b)。从遗传距离分析发现,山西汉族与吉黑汉族之间的遗传距离最近(?0.0001),与台湾群体(0.0152)之间的遗传距离相对较远。结果表明该17个Y-STR基因座在山西汉族群体中具有丰富的遗传多态性,对建立Y染色体STR数据库、研究群体遗传学和进行法医学应用有重要意义。     

甘肃裕固族HLA—DRB1基因多态性及其族源分析

目的：研究甘肃裕固族HLA—DRB1基因的多态性,探讨裕固族的起源、迁徙及其与其他民族的关系。方法：应用PCR-SSP基因分型技术,对54例裕固族个体进行了HLA-DRB1位点的基因分型并进行相应等位基因频率的比较。结果：甘肃裕固族HLA-DRB1位点共检出了14种等位基因,其中高频基因为DR5（0、2115）,DR4（0、1346）和DR7（0．1250）,低频的等住基因为DR14（0．0096）和DR13（0．0192）;裕固族人HLA-DRB1座位等位基因总的分布格局与蒙古族最接近,与云南黎族则相差较远。结论：对裕固族和我国各地人群的HLA-DRB1频率进行了聚类分析,极为相似的HLA-DRB1背景提示裕固族和蒙古族之间密切的遗传关系。     

中国南方汉族群体MPSⅠ型KpnⅠ酶切位点的遗传多态性

为研究中国汉族群体IDUA基因球KｐｎⅠ酶切位点的遗传多态性以及该位点等位基因片段传递的规律,采用PCR－RFLP技术,对162例无血缘关系的健康中国汉人的324条染色体进行检测,另又对5个家系16位成员进行同样的检测,然后用X2检验进行统计学处理。结果表明,等位基因A1频率为0．17,等位基因A2频率为0．83,杂合率为29％;A1、A2的传递规律与理论上预计的完全符合。认为中国汉族群体IDUA基因KｐｎⅠ酶切位点也具有遗传多态性,并且与国外报道的无显著性差异;A1、A2在世代中的传递完全符合孟德尔遗传规律。     

应用IdentifilerTM系统对湖南人群中OL等位基因的观察与分析

应用IdentifilerTM系统和ABI310型遗传分析仪,对湖南人群中3 423例无关个体进行基因分型,筛选出OL等位基因,并对其分布及构成进行分析.结果显示在3 423例个体基因分型中,发现12种OL等位基因,分布于D13S317、D19S433、D21S11、D3S1358、D7S820和FGA等6个基因座,各基因座OL等位基因的种类数目为1～3个,位点频率为0.292‰～9.641‰.通过以上研究,可对IdentifilerTM系统群体遗传多态性数据进行有效的补充和完善,从而使其更好地应用于人类生物学、法医遗传学等领域.     

四川彝族和新疆维族HLA-B位点基因多态性分析

应用PCR-SSP(Polymerase Chain Reaction-Sequence Specific Primer) 方法对无亲缘关系的106位四川彝族样品和110位新疆维族样品进行HLA-B基因分型。在彝族样品中共检出20个等位基因,其中高频率的等位基因为B*40（0.2028）、B*15（0.1604）、B*51(0.1274),低频率的等位基因为B*47 (0.0189)、B*27(0.0142)、B*44(0.0142)、B*18(0.0094)和B*78(0.0047)。在维族样品中共检出27个等位基因,其中高频率的等位基因为B*35 (0.1136)和B*51（0.1136）,低频率的等位基因为B*41（0.0045）、B*56（0.0045）和B*78（0.0091）。经χ2检验,两个民族群体的基因型分布均符合Hardy-Weinberg平衡。经遗传分析,四川彝族群体HLA-B基因座杂合度(H)、个体识别率(DP)和非父排除率(EP)分别为0.8977、0.9661和0.8009;维族群体的H、DP和EP分别为0.9372、0.9857和0.8732。本研究获得了四川彝族和新疆维族HL A-B基因座基因频率数据,为临床器官移植配型、人类学、法医学及疾病关联性研究提供了重要的群体遗传学资料。     

HLA-A gene polymorphism defined by high-resolution sequence-based typing in 161 Northern Chinese Han people

Human leukocyte antigen (HLA) system is the most polymorphic region known in the human genome. In the present study, we analyzed for the first time the HLA-A gene polymorphisms defined by the high-resolution typing methods-sequence-based typing (SBT) in 161 Northern Chinese Han people. A total of 74 different HLA-A gene types and 36 alleles were detected. The most frequent alleles were A*110101 (GF=0.2360), A*24020101 (GF=0.1646), and A*020101 (GF=0.1553); followed by A*3303 (GF=0.1180), A*3001 (GF=0.0590),     

High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

Background

Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort.

Methodology/Principal Findings

Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group.

Conclusions

At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates.     

新疆维吾尔族和汉族亚甲基四氢叶酸还原酶基因多态性研究

目的:研究新疆维吾尔族、汉族两民族亚甲基四氢叶酸还原酶(Methyleneterahyofolate reductase MTHFR)基因多态性的分布情况,获取新疆维吾尔族与汉族MTHFR 1298位群体遗传学数据。方法:应用PCR-RFLP技术检测新疆维吾尔族及汉族MTHFR1298位多态性位点基因频率及基因型频率。结果:新疆维吾尔族、汉族MTHFR 1298位C等位基因分布频率分别为12%、23%,P<0.05有统计学差异性,且新疆维吾尔族MTHFR 1298位C等位基因分布频率与现有报道的少数民族贵州苗族、布依族具有统计学差异。结论:MTHFR 1298位多态性在不同民族具有差异性:MTHFR 1298位多态性在新疆维吾尔族和汉族有民族差异;新疆新疆维吾尔族MTHFR 1298位C等位基因频率与贵州苗族、布依族少数民族之间具有民族差异性。     

新疆维吾尔族HLA-Cw基因座遗传多态性调查 The Study of HLA-Cw Polymorphism in Uygur Population

采用序列特异性寡核苷酸探针杂交技术（PCR-SSOP）对146位新疆维吾尔族无关个体HLA-Cw基因座进行基因分型,研究该民族HLA-Cw基因座遗传多态性,建立新疆维吾尔族HLA-Cw基因频率数据库。检出18种等位基因,基因频率分布在0.0069~02460,其中HLA-Cw*04、07、08、14基因频率比较高,基因频率分别为02460、0.1151、0.1010、0.1202,共占新疆维吾尔族可检出等位基因的58.23%,PCR-SSOP分型技术使新疆维吾尔族HLA-Cw基因座空白基因频率降至0.0064。经χ2检验,基因型分布符合Hardy-Weinberg平衡定律。建立民族HLA-Cw基因座基因频率数据库,为临床器官移植配型、人类学、法医学提供重要的群体遗传学资料。 Abstract:The HLA-Cw loci polymorphism in Uygur population was investigated using the PCR- sequence specific oligonucleotide probe (SSOP) method,and the genetic database on the distribution of gene frequency of the HLA-Cw loci was established.From 146 individuals of Uygur population,18 HLA-Cw alleles were detected.The gene frequency was from 0.0069 to 0.2460.The four most common alleles were HLA-Cw*04(24.60%)、07(11.51%)、08(1010%)、14(12.02%),and they covered 58.23% of total alleles detected from Uygur population.We have made a survey of HLA-Cw alleles frequencies in a Uygur population,with blank frequency being lowered to 0.0064.The distribution of genotype frequencies met the law of Hardy-Weinberg equilibrium by hi-square test.The frequency data can be used in forensic and paternity tests to estimate the frequency of a DNA profile in the Uygur population,transplant matching and anthropology.     

An Analysis of HLA-A, -B,and -DRB1 Allele and Haplotype Frequencies of 21,918 Residents Living in Liaoning,China

HLA-A, -B and -DRB1 allele frequencies and their haplotype frequencies in 21,918 Chinese residents living in Liaoning Province, who were registered as volunteer donors of China Marrow Donor Registry, were investigated. They are composed of 93.37% Han Chinese, 5.1% Manchus, 0.57% Mongols, 0.46% Hui persons, 0.29% Koreans and 0.14% Xibe ethnic group. In total eighteen different HLA-A alleles, forty-eight different HLA-B alleles and fourteen different HLA-DRB1 alleles have been identified. Their frequencies are in agreement with the Hardy-Weinberg equilibrium. For Han Chinese in Liaoning, 1,534 different HLA-A-B-DRB1 haplotypes were identified, with a frequency of higher than 0.01%. A*30-B*13-DRB1*07, A*02-B*46-DRB1*09 and A*02-B*13-DRB1*12 are the most frequent haplotypes among Liaoning Han. While Liaoning Han, Liaoning Manchu, Liaoning Mongol, Liaoning Hui and Liaoning Korean share the northern Han characteristic haplotypes, all minority ethnic groups with the exception of Liaoning Manchu have developed their own unique HLA profiles. This dataset characterizes the HLA allele and haplotype frequencies in the Liaoning area and suggests that it is different from those in other parts of China and ethnic groups, which implicates transplant donor searching strategies and studies on population genetics.     

HLA-DR polymorphism in a Senegalese Mandenka population: DNA oligotyping and population genetics of DRB1 specificities.

HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro PCR amplification detects HLA allelic polymorphisms for all class II loci. A detailed HLA-DR oligotyping analysis of 191 individuals from a geographically, culturally, and genetically well-defined western African population, the Mandenkalu, reveals a high degree of polymorphism, with at least 24 alleles and a heterozygosity level of .884 for the DRB1 locus. The allele DRB1*1304, defined by DNA sequencing of the DRB1 first-domain exon, is the most frequent allele (27.1%). It accounts for an unusually high DR13 frequency, which is nevertheless within the neutral frequency range. The next most frequent specificities are DR11, DR3, and DR8. Among DRB3-encoded alleles, DR52b (DRB3*02) represents as much as 80.7% of all DR52 haplotypes. A survey of HLA-DR specificities in populations from different continents shows a significant positive correlation between genetic and geographic differentiation patterns. A homozygosity test for selective neutrality of DR specificities is not significant for the Mandenka population but is rejected for 20 of 24 populations. Observed high heterozygosity levels in tested populations are compatible with an overdominant model with a small selective advantage for heterozygotes.     

中国西北地区汉,回,维,藏民族HLA—DRB基因多态性的研究

按照第１１届国际相容性抗原研讨会工作会议ＨＬＡⅡ类ＰＣＲ－ＳＳＯ分型标准和美国国立骨髓供者计划组织对ＨＬＡ ＤＲＢ位点等位基因分型要求,设计合成１对引物,扩增ＨＬＡ ＤＲＢ ＤＮＡ片段,长度为２５６ｂｐ,设计合成不同片段大小探针２７种,可检出ＤＲＢ座位上ＤＲＢ１的３９种等位基因,ＤＲＢ３的３种等位基因,ＤＲＢ４的１种等位基因和ＤＲＢ５的３４种等位基因。     

Genetic link between Chaoshan and other Chinese Han populations: Evidence from HLA-A and HLA-B allele frequency distribution

The genetic polymorphism of HLA-A and HLA-B loci was investigated in 505 Chaoshanese using PCR-SSP method. Among the HLA-A alleles detected, A*11 (35.64%) was most frequent, followed by A*02 (31.78%). Of 34 HLA-B alleles tested, 30 were observed, in which B*60 (21.68%), B*46 (14.46%), and B*58 (10.69%) were highly predominant. Comparison was made with other nine Chinese Han ethnic groups covering the Mainland China, Taiwan, Hong Kong, and Singapore. The high frequent alleles found in Chaoshanese were also common in other Chinese groups compared though the frequency levels varied from group to group. The phylogenic tree analysis based on the HLA-A and -B allele frequencies of all the 10 Chinese ethnic groups revealed that Chaoshanese, while clustering in general with the southern China-related Han Chinese, had the highest affinity to the Mainland Minnanese, but separated distinctively from the northern Han Chinese. The study, however, was yet to confirm the hypothesis of the Central Plains Han origin of Chaoshanese. Interestingly, the alleles (B*46, B*38, and B*58) and the related haplotypes (A*02-B*46 and A*33-B*58) that are positively associated with nasopharyngeal carcinoma (NPC), a disease prevailing predominantly among southern Chinese, were always at much higher frequencies among southern Chinese than among northern Chinese, whereas A*31 and B*13, the two alleles with highly protective effects for NPC, and the associated haplotype A*30-B*13 were predominantly high in northern Chinese. The different genetic background between northern and southern China may explain, at least partially, the prevalence of NPC among southern Chinese.     

云南澜沧拉祜族HLA-DRB1基因多态性研究

采用我们改进的高分辨率基于内含子的PCR-SBT分型方法,首次检测云南拉祜族HLA-DRB1基因多态性。在55例拉祜族个体中共检出16种HLA-DRB1等位基因,最常见的DRB1等位基因是HLA-DRB1*12021、09012、15011,基因频率分别为30.909%、15.455%、13.636%,共占拉祜族可检出等位基因的60%,其中DRB1*0413、11081、1312、1418、1504首次在我国人群中检出,并且在世界各地人群中也比较罕见。对拉祜族和世界各地人群的HLA-DRB1频率进行了比较,分析了HLA-DRB1等位基因在各人种中的分布特点,并用Neighbor-joining法进行了聚类分析。比较分析的结果显示拉祜族明显属于中国南方族群,未显示出其族源来自北方的痕迹。对此遗传数据和民族学、历史学研究的矛盾,做了初步的分析。 Abstract:The HLA-DRB1 gene polymorphism in Lahu ethnic of Yunnan,China was the first time investigated using high resolution PCR-SBT method,which is based on sequences of HLA-DRB1 Intron 1 and Intron 2 and with our improvement.From 55 individuals of Lahu ethnic 16 DRB1 alleles were detected.The three most common alleles were HLA-DRB1*12021(30.909%),09012(15.455%),15011(13.636%),and they covered 60% of the total alleles detected from Lahu ethnic.HLA-DRB1*1413,*11081,*1312,*1418,*1504 were the first time detected in the Chinese,and were very rare in worldwide ethnic groups.With comparison of HLA-DRB1 gene frequencies between various ethnic groups we analysized the characteristics of HLA-DRB1 gene distribution in worldwide populations,and constructed the phylogenetic tree by Neighbor-joining method and Nei measure of genetic distance.The result showed Lahu ethnic obviously belong to the Chinese South ethnic groups and can't trace its origin from northern groups with the HLA-DRB1 genetic data.The preliminary explanations about the contradiction were given in this paper.