中国南方汉族人群DNA错配修复酶hMSH2基因遗传多态性分析

目的 获取DNA错配修复酶hMSH2基因在中国南方汉族人群中的基因型和基因频率等群体遗传学资料。方法 收集163名中国南方汉族人群的基础资料及血液标本，抽提血液DNA，用多重PCR法扩增hMSH2基因第6、第7外显子，并进行单链构象多态性分析及DNA序列分析。结果 检测出hMSH2基因第7外显子上的C18、A82、B39 3种基因突变类型，频率分别为0．0184、0．0031、0．0031，经检验符合Hardy—Weinberg平衡(P＞0．05)；C18型突变杂合度最高(0．0361)。结论 中国南方汉族人群中hMSH2基因第7外显子上存在3种突变型等位基因，其中C18型突变频率最高，是一种有用的遗传标记。     

中国汉族人群DC-SIGN和DC-SIGNR基因遗传多态性

目的了解中国汉族人群DC-SIGN和DC-SIGNR基因颈区重复序列的遗传多态性分布，获得相应位点的汉族人群的遗传学数据。方法应用PCR技术、琼脂糖凝胶电泳结合测序对DC-SIGN和DC-SIGNR基因的颈区重复序列分型，计算DC-SIGNR的多态信息含量。结果DC-SIGN多态性低，颈区绝大多数为等位基因7重复，该等位基因频率为0．9808，但亦检出少量的等位基因4、5、6、8等变异，而美国白人只含有等位基因6、8变异；DC-SIGNR存在高度多态性，多态信息含量为0．5312，存在4、5、6．7、8、9等位基因，检出16种基因型。6／5、7／4、7／5、7／6、7／7、9／5、9．／7、9／9基因型和5、6、7、9等位基因频率在中国汉族人群和美国白人中的分布构成差异有统计学意义（P〈0．01），与美国白人比较，中国汉族人群似乎存在更多的插入突变。结论中国汉人的DC-SIGN和DC-SIGNR基因型分布和基因频率与美国白人相比其差异有统计学意义，并有其独特的群体遗传学特征。     

河北省汉族人群六个短串联重复序列基因座的遗传多态性

目的 对河北汉族群体6个短串联重复序列(short tandem repeat，STR)基因频率研究，以期得到河北汉族群体D7S820、D19S253、D12S391、D5S818、D16S539和D8S1179基因座的群体遗传学数据。方法 随机抽取173名河北省汉族人群无血缘关系个体的静脉血，应用PCR技术扩增上述6个短串联重复序列基因座，采用高分辨的聚丙烯酰胺凝胶垂直板电泳，银染显色分析。结果 得到了河北汉族这6个位点的遗传多态分布。D7S820、D19S253、D12S391、D5S818、D16S539、D8S1179基因座的杂合度分别为：0．828、0．757、0．769、0．837、0．785、0．852。个体识别率分别为：0．914、0．919、0，940、0．909、0．917、0．944。非父排除率分别为：0．618、0．740、0．801、0．557、0，655、0．696。遗传多态性信息量分别为：0．771、0．760、0、762、0．708、0．776、0．794。结论 上述6个STR基因座基因频率分布与Hardy-Weinberg平衡吻合良好，在河北汉族群体中具有较高的非父排除率与个体识别率，在群体遗传学研究及法医学应用中有较高价值。     

中国汉族人群D11S2010基因座的遗传多态性研究

短串联重复序列 (short tandem repeats,STR)广泛存在于人类基因组中 ,是由 2～ 7bp核心序列串联重复构成 ,它的多态性主要由核心序列的数目变异所致 [1 ]。作为第 2代 DNA遗传标记 ,STR位点已广泛用于法医学个人识别和亲子鉴定。近年来 ,国内外学者为开发 STR位点做了许多工作 ,对于中国人群在不同民族及不同地区的遗传多态性也有一些报道[2 - 5] 。我们采用 PCR、PAG垂直电泳和银染的方法 ,对中国河北 16 8名汉族健康无关个体 D11S2 0 10位点进行了调查 ,同时对 10个家系进行了分析 ,获得了汉族人群 D11S2 0 10基因座群体遗传学…     

湖南汉族人群HLA-DP、-DQ位点等位基因多态性与鼻咽癌的相关性

目的 探讨湖南汉族人群HLA—DP、HLA—DQ位点等位基因多态性与鼻咽癌遗传易感性之间的关系。方法 应用聚合酶链反应—特异性寡核苷酸探针基因分型技术对87例湖南汉族鼻咽癌患者与91名健康对照作HLA—DPAl、—DPBl、—DQAl及—DQBl的基因分型，采用x^2检验比较两组各位点等位基因频率，单倍型频率分布的差异。结果 发现鼻咽癌组DPAl*0201、DPBl*1901、DQAl*0201较对照组明显降低，DPBl*0402、DQAl*0101较对照组明显升高；单倍型DPAl*0201—DPBl*1401及DQAl*0201—DQBl*0201较对照明显降低；但P值经Bonferroni校正后，差异均无显著性(Pc＞0．05)。结论 湖南汉族人群HLA—DP和—DQ位点与鼻咽癌无明显相关，与以往用受累同胞对方法在鼻咽癌家系中未能证实鼻咽癌易感基因与HLA—DP和—DQ位点连锁的结果一致。     

中国湖北地区汉族人群TNF遗传多态性研究

目的：探讨中国湖北地区汉族人群中TNF微卫星遗传多态性分布。方法：收集湖北地区164名无血缘关系健康个体的静脉血,提取DNA,应用PCR结合变性聚丙烯酰胺凝胶高压电泳和AgNO3染色,对TNF微卫星进行分型,并将PCR产物克隆及测序鉴定。结果：TNFb检测到7个等位基因,11种基因型;TNFe检测到4个等位基因,7种基因型。TNFb和TNFe位点多态信息含量（PIC）分别为0．67和0．33,两者基因型分布皆符合Hardy-Weinberg平衡定律。统计分析显示,中国汉族人群TNFb、TNFe等位基因频率分布与欧美白种人均有显著性差异（P＜0．05）。结论：TNFb和TNFe等位基因频率分布具有种族的差异性。     

汉族人群谷胱甘肽-S-转移酶M1、T1基因多态性分析

目的 分析汉族人群谷胱甘肽-S-转移酶M1、T1(GSTM1,GSTT1)的基因多态性分布。方法样本为60名唐山地区汉族人群，采用多重等住基因聚合酶链反应(PCR)方法分析GSTM1和GSTT1基因多态性。结果 GSTM1缺失型和GSTT1缺失基因型频率分别为33．3％和11．7％，同时具有GSTM1缺失型和GSTT1缺失型的个体频率为1．7％。结论唐山地区GSTM1,GSTT1基因呈多态性分布，其等位基因和基因型频率不同于其他种族。     

海南汉族人群九个纤维蛋白原基因多态性及其与血浆纤维蛋白原水平的关系

目的 调查海南汉族健康人群αTaqⅠ和βBclⅠ、HinfⅠA／C、448G／A、βBsmA ⅠG／C、＋1689T／G、-148C／T、-249C／T、-455G／A多态性的等位基因频率及其与血浆纤维蛋白原（fibrinogen，Fg）水平的关系。方法 用比浊法测定238名健康个体的血浆Fg浓度，用PCR-限制性片段长度多态性方法及测序法分析多态性基因型，并用协方差分析比较9个位点的基因型与血浆Fg水平的关系。结果 海南汉族人群αTaqⅠ、βBclⅠ、HinfⅠA／C、C448、βBsmAⅠG／C、＋1689T／G、-148C／T、-249C／T、-455G／A稀有位点的等位基因频率分别为0．445、0．239、0．134、0．235、0．273、0．241、0．265、0．441、0．254，9个位点之间存在连锁不平衡；在总人群中，-455GA和AA基因型、-148CT和TT基因型、αTaqⅠT1T1基因型组的血浆Fg水平比野生型组高（P值均〈0．01）；在男性人群中，-455GA和AA基因型、-148CT和TT基因型、αTaqⅠT1T1、αTaqⅠT1T2基因型组的血浆Fg水平比野生型组高（P值均〈0．01）。在女性人群中，携带稀有位点A^-455、T^-148、αTaⅠT1的基因型组与野生型组之间的血浆赡水平差异无统计学意义。结论 在9个多态性位点之间存在连锁不平衡；A^-455、T^-148、αTaqⅠT1位点与血浆Fg水平增高关联，β-Fg-455G／A、-148C／T及α-TaqⅠ多态性与男性血浆Fg水平关联。     

中国汉族人群TNF-α基因启动子区的多态性研究

目的：研究中国汉族人群TNF-α基因启动子区的基因多态性。方法：采用PCR-SBT（PCR Sequencing Based Typing）方法进行TNF-α基因启动子区的多态检测。结果：采用PCR-SBT方法可以成功获得TNF-α基因启动子区的多态性结果并能够发现新的多态性位点；本次研究发现中国汉族人群TNF-α基因启动子区的多态性位点有：-1031、-863、-857、-572、-308、-238、-204和-163，其中-572和-204的多态性位点为首次报道；我国汉族人群该区域的核酸差异性为（11.00±0.46）×10-4，低于非洲人群；与Malawi人群相比，我国汉族人群-1031C、-308A、-238A出现频率较低，而-857T的频率却较高；与Gambian人群相比，-863A和-857T出现频率较高，-308A出现频率较低；我国汉族人群TNF-α基因启动子区的-1031C、-863A、-857T与-572C、-308A、-238、-204C、-163C有相关性。结论：采用PCR-SBT方法可以成功对TNF-α基因启动子区的基因多态性进行研究，我国汉族人群TNF-α基因启动子区的基因多态性可能存在独特的特点。     

载脂蛋白E基因多态性在云南省德宏州傣族人群的分布

目的　探讨云南省德宏州傣族人群和昆明汉族人群载脂蛋白E(apolipoprotein E,apo E)基因多态性分布情况。方法　收集171名德宏傣族和71名昆明汉族人群基因组,通过聚合酶链反应-限制性片段长度多态性方法检测apo E基因第4外显子第112位和15 8位的多态性。结果　傣族组apo Eε2 / 2、ε2 /3、ε2 / 4、ε3/ 3、ε3/ 4、ε4 / 4基因型频率依次为:0 .0 0 6、0 .111、0 .0 0 6、0 .789、0 .0 88、0 .0 0 0 ;汉族组依次为:0 .0 0 0、0 .16 9、0 .0 14、0 .718、0 .0 99、0 .0 0 0。apo Eε2、ε3、ε4等位基因频率在傣汉两民族中依次为:0 .0 6 4、0 .889、0 .0 4 7;0 .0 92码、0 .85 2、0 .0 5 6 (P>0 .0 5 )。结论　apo E基因型频率和等位基因频率均存在着民族、种族差异。与国内其它少数民族比较,德宏傣族人群apo Eε2等位基因频率显著低于壮族(P<0 .0 1) ;ε3等位基因频率显著高于朝鲜族、回族、蒙古族、壮族(P<0 .0 5 ) ,极显著高于维吾尔族(P<0 .0 1) ;ε4等位基因显著低于鄂伦春族(P<0 .0 5 ) ,极显著低于维吾尔族、鄂温克族(P<0 .0 1)。与不同种族人群比较,德宏傣族人群apo E基因多态性分布与日本人接近(P>0 .0 5 ) ,而与新加坡、欧美国家人群有较大的差异性。     

MICA genetic polymorphism and HLA-A,C,B,MICA and DRB1 haplotypic variation in a southern Chinese Han population: identification of two new MICA alleles, MICA*060 and MICA*062

In this study, 201 healthy, unrelated Han subjects in Hunan province, southern China, were investigated by sequence-based typing (SBT) for the allelic variation of the human major histocompatibility complex (MHC) class I chain-related gene A (MICA). Nineteen MICA alleles were observed, among which MICA*008:01 predominated with gene frequency of 30.35%. There was significant linkage disequilibrium (LD) of MICA*012:01 with HLA-B*54 and HLA-B*55, which was not observed in a northern Chinese Han population. Haplotype HLA-A*11-C*07-B60-MICA*008:01 (9.16%) was highly specific to this southern Chinese Han population. The most common five-locus haplotype in this population was HLA-A*02-C*01-B*46-MICA*010-DRB1*09 (8.73%). A new MICA allele, MICA*060, was identified on an HLA-A*02-C*01-B*55:02-DRB1*14 haplotype through extended family analysis. MICA*060 has probably arisen from MICA*012:01. Another new MICA allele, MICA*062, was identified by screening 1432 subjects using polymerase chain reaction-sequence-specific priming technology. MICA*062 has probably derived from MICA*010. Of particular interest is that MICA*062 was carried on an HLA-C*08-B*48:01-DRB1*14 haplotypic segment, as HLA-B*48 has been consistently shown to be primarily linked to MICA gene deletion in east Asian populations. Our results provide new insight into MICA genetic polymorphism in human populations. The findings reported here are of importance for future studies on the potential role of MICA in allogeneic organ transplantation and disease association in populations of Chinese ancestry.     

Distribution of MICA haplotypes in a Chinese Han population

The MICA gene encodes nonclassical major histocompatibility complex class I molecules, centromeric to HLA-B and telomeric to HLA-DRB1. The MICA genes are polymorphic. The immune response against MICA may correlate with a decrease in graft survival after transplantation. However, data on the frequency of MICA polymorphisms in different populations are limited. In this study, we determined MICA allelic frequencies in a Han population living in Guangdong Province in south China. A total of 15 MICA alleles were identified using sequence-based typing. The most frequent allele was MICA*010 (22.22%), followed by MICA*002:01(18.56%), MICA*008:01(16.32%), and MICA*019(14.93%). The MICA null gene (MICA*Del) exhibited a frequency of 1.743% in this population. MICA and HLA, MICA-HLA-B, and MICA-HLA-A/HLA-B/HLA-DRB1 haplotype frequencies were estimated. The most common 2-, 3- and 4-locus haplotypes were HLA-B*40:01-MICA*008:01 (13.70%), HLA-A*11:01-B*40:01-MICA*008:01(8.25%), and HLA-A*33:03-B*58:01-DRB1*03:01-MICA*002:01(5.22%). A new MICA allele, MICA*061, was identified and appears to be evolutionarily related to MICA*012:01. This study provides high-resolution information on the distribution of haplotypes with MICA, HLA-A, HLA-B, and HLA-DRB1 in China. This information should help determine the mechanisms underlying diseases and allotransplant rejection associated with MICA polymorphisms in the southern Chinese Han population.     

MICA‐129 Met/Val polymorphism could be a genetic biomarker for Familial Breast Cancer in the Tunisian population

Identification of candidate genes associated with susceptibility of breast cancer can have a significant impact at a cancer management national healthcare systems level, making genetic testing more affordable and cost‐effective. We have previously shown that the major histocompatibility complex class I‐related chain A (MICA) was related to breast cancer and plays an important role in modulating immune response mechanisms through NKG2D receptor activation. Compared to our previous study, in this work, we recruited a new cohort composed of 354 unrelated Tunisian women affected by breast cancer and 380 age‐matched women as controls, all genotyped for MICA‐129 Met/Val (rs 1051792). Subsequently, we exanimated the distribution of this polymorphism in ten families. As a result, an association was found between the Val allele and Val/Val genotype and the risk of breast cancer (p = 2.5 × 10^–15; OR = 2.40; p = 6.5 × 10^–13; OR = 3.03, respectively). Stratified analysis with age and family history of cancer revealed an association between the Val/Val genotype and younger patients <40 years (p = .003; OR = 2.03). Among those patients having a family history of cancer, 68% had a Val/Val genotype (p = .02; OR = 1.82). In the family study, an analyse of pedigrees revealed that the majority of families showed the development of breast cancer at a young age. Moreover, all patients diagnosed with early‐onset breast cancer had a Val/Val genotype. Our results lead us to propose that this polymorphism may be an inherited genetic biomarker contributing to an increased breast cancer risk in Tunisian women.     

中国南方汉族和苗族人群hPARP1基因遗传多态性

目的检测人类聚腺苷二磷酸核糖聚合酶1[poly（ADP-ribose）polymerase 1，PARP1]基因的基因型和基因频率在中国南方汉族和苗族人群中的分布。方法收集187名中国南方汉族和210名苗族人的血液DNA，用PCR法扩增hPARP1基因4个外显子，并进行单链构象多态性分析。结果用PCR成功扩增出第12、13、16、17外显子，片段长度分别为253bp、313bp、175bp、362bp，在187名中国南方汉族和210名苗族人群中，分别有3人和9人检测出hPARP1基因第12、13、16和17外显子上各有1种基因突变，分别为Phe548Ser、Ala683Ser、Asp798Tyr、His808Arg。结论中国南方汉族和苗族人群中hPARP1基因第12、13、16和17外显子上存在突变型等位基因。     

广东汉族人群MICA和MICB微卫星多态性分布

目的　调查广东地区汉族人群 MICA基因第 5外显子和 MICB基因第 1内含子微卫星多态性分布。方法　应用聚合酶链反应和荧光 ( 6 - FAM)自动化检测技术 ,对广东地区共 10 6名无亲缘关系样本进行 MICA和 MICB微卫星基因分型 ,并计算这两个微卫星的基因频率、基因型频率、个体鉴别力、期望杂合性、多态性信息含量和非父排除率。结果　MICA和 MICB微卫星基因型分布符合 Hardy- Weinberg平衡。MICA A5基因频率最高为 0 .2 877,A4基因频率则最低为 0 .132 1;A5 - 5 .1( 14 .15 % )和 A5 - 5 ( 10 .38% )基因型分布频率较高。 MICB CA14等位基因频率最高为 0 .32 5 5 ,CA19、CA2 8等位基因频率最低为0 .0 0 4 7,未检出 CA2 7。 CA14 - CA14 ( 14 .15 % )基因型分布频率较高。结论　 MICA基因第 5外显子和MICB基因第 1内含子微卫星适合作为中国人群的遗传标志 ,用于人类学、遗传疾病基因连锁分析、法医学亲子鉴定和个体识别等研究领域     

MICA-STR, HLA-B haplotypic diversity and linkage disequilibrium in the Hunan Han population of southern China

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. This study was aimed to investigate the haplotypic diversity and linkage disequilibrium between human leukocyte antigen (HLA)-B and (GCT)(n) short tandem repeat in exon 5 of MICA gene (MICA-STR) in a southern Chinese Han population. Fifty-eight randomly selected nuclear families with 183 members including 85 unrelated parental samples were collected in Hunan province, southern China. HLA-B generic typing was performed by polymerase chain reaction-sequence-specific priming (PCR-SSP), and samples showing novel HLA-B-MICA-STR linkage were further typed for HLA-B allelic variation by high-resolution PCR-SSP. MICA-STR allelic variation and MICA gene deletion (MICA*Del) were detected by fluorescent PCR-size sequencing and PCR-SSP. Haplotype was determined through family segregation analysis. Statistical analysis was applied to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities and seven MICA-STR allelic variants were observed in 85 unrelated parental samples, the most predominant of which were HLA-B*46, -B60, -B*13, and -B*15, and MICA*A5, MICA*A5.1 and MICA*A4, respectively. Genotype distributions of HLA-B, MICA-STR loci were consistent with Hardy-Weinberg proportions. The HLA-B-MICA-STR haplotypic phases of all 85 unrelated parental samples were unambiguously assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations, nine of them have not been reported in the literature. Significant positive linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA-B*13 and MICA*A4, HLA-B*38 and MICA*A9, HLA-B*58 and MICA*A9, HLA-B*46 and MICA*A5, HLA-B*51 and MICA*A6, HLA-B*52 and MICA*A6, and HLA-B60 and MICA*A5.1, were observed. HLA-B*48 was linked to MICA*A5, MICA*A5.1 and MICA*Del. HLA-B*5801-MICA*A10 linkage was found in a family. Our data indicated a high degree of haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B in a southern Chinese Han population, the data will inform future studies on anthropology, donor-recipient HLA matching in clinical transplantation and HLA-linked disease association.     

南方汉族人特应性皮炎中间丝聚合蛋白基因多态性检测与分析

目的 探讨中间丝聚合蛋白( filaggrin,FLG)基因多态性与南方汉族人特应性皮炎(atopic dermatitis,AD)的相关性.方法 提取50例南方汉族AD患者及100名健康对照者的基因组DNA,采用PCR及直接测序法,对FLG基因已报道的13个单核苷酸多态性(3321 delA、441 delA、1249insG、E1795X、S3296X、R501X、2282 del4、R2447X、S2889X、7945 delA、3702 delG、Q2417X、R4307X)进行测序.结果 14例(28％)AD患者检测到FLG 3321 delA多态性位点,6例(12％) AD患者检测到FLG 441 delA多态性位点,健康对照组无1例检测到该多态性位点.患者组及对照组均未检测到FLG( 1249insG、E1795X、S3296X、R501X、2282 del4、R2447X、S2889X、7945 delA、3702 delG、Q2417X、R4307X)基因多态性.结论 FLG基因可能与南方汉族人群AD易感性相关.     

HLA class I chain-related MICA and MICB genes polymorphism in healthy individuals from the Bulgarian population

Although human leukocyte antigen (HLA) gene polymorphism has been investigated in many populations around the world, the data on MHC class I chain-related (MIC) genes are still limited. The present study is aimed to analyze the allelic polymorphism of MICA and MICB genes and haplotype associations with HLA-B locus in 132 healthy, unrelated individuals from the Bulgarian population by next generation sequencing (NGS). A total of 36 MICA and 16 MICB alleles were observed with the highest frequency detected for MICA*008:01 (17.1%) and MICB*005:02 (32.4%). Further, two and three-loci haplotype frequencies and pairwise linkage disequilibrium were estimated. Highly significant global linkage disequilibrium was found between either HLA-B and MICA and MICB genes. This is the first study on MICA and MICB allelic polymorphism, linkage disequilibrium, and haplotype polymorphism in the Bulgarian population. These results will allow for better characterization of the genetic heterogeneity of the Bulgarian population and could contribute to further analyses on MICA and MICB clinical significance.