浙江汉族人群HLA-DPA1和-DPB1基因多态性分析

目的 检测浙江地区汉族人群HLA-DPA1和HLA-DPB1等位基因及单倍型频率.方法 应用PCR-直接测序分型法对100名健康、无血缘关系的浙江汉族人外周血标本进行HLA-DPA1和HLADPB1等位基因分析.结果 在100份标本中检出8个HLA-DPA1等位基因和19个HLA-DPB1等位基因.HLA-DPA1等位基因频率较高的依次为DPA1*020202(47.0%)、DPA1*010301(38.5%)和DPA1*020101(10.5%).HLA-DPB1等位基因中,频率较高的依次为DPB1*0501(39.5%)、DPB1*020102(13.5%)和DPB1*040101(13.0%).连锁分析发现共有44个HLA-DPA1-DPB1单倍型,单倍型频率最高为DPA1*020202-DPB1*0501(29.5%).结论 浙江地区汉族人群HLA-DPA1和DPB1基因座等位基因具有丰富的多态性,2个基因座呈现连锁不平衡.     

广东汉族人群HLA-Cw基因多态性分析

检测HLA Cw在广东汉族人群中的基因频率 ,与其他人群进行比较 ,分析该人群HLA Cw等位基因多态性及其特点。骨髓移植供者 15 8例 ,抗凝血提取DNA ,半量全自动PCR RSSO分型检测Cw。结果显示 ,广东汉族人群HLA Cw基因频率分布由高至低依次为 :Cw 0 3(0 2 5 80 ) >Cw 0 7(0 1887) >Cw 0 1(0 1732 ) >Cw 0 8(0 10 70 ) >Cw 14 (0 0 6 5 4 ) >Cw 0 4(0 0 5 87) >Cw 15 (0 0 4 5 3) >Cw 12 (0 0 387) >Cw 0 6 (0 0 32 2 ) >Cw 0 5 (0 0 12 7) >Cw 16 (0 0 0 32 )。Hardy Weinberg平衡检验 χ2 =6 0 35 ,υ =5 4 ,P >0 1。表明广东汉族群体Cw 0 3、 0 7、 0 1、 0 8出现频率较高 ,该人群Cw等位基因处于遗传平衡状态 ,具有较为丰富的多态性及特点。     

浙江汉族人群HLA-DPA1和-DPB1基因多态性分析

目的 检测浙江地区汉族人群HLA-DPA1和HLA-DPB1等位基因及单倍型频率.方法 应用PCR-直接测序分型法对100名健康、无血缘关系的浙江汉族人外周血标本进行HLA-DPA1和HLADPB1等位基因分析.结果 在100份标本中检出8个HLA-DPA1等位基因和19个HLA-DPB1等位基因.HLA-DPA1等位基因频率较高的依次为DPA1*020202(47.0%)、DPA1*010301(38.5%)和DPA1*020101(10.5%).HLA-DPB1等位基因中,频率较高的依次为DPB1*0501(39.5%)、DPB1*020102(13.5%)和DPB1*040101(13.0%).连锁分析发现共有44个HLA-DPA1-DPB1单倍型,单倍型频率最高为DPA1*020202-DPB1*0501(29.5%).结论 浙江地区汉族人群HLA-DPA1和DPB1基因座等位基因具有丰富的多态性,2个基因座呈现连锁不平衡.     

浙江汉族人群HLA-DPA1和-DPB1基因多态性分析

目的 检测浙江地区汉族人群HLA-DPA1和HLA-DPB1等位基因及单倍型频率.方法 应用PCR-直接测序分型法对100名健康、无血缘关系的浙江汉族人外周血标本进行HLA-DPA1和HLADPB1等位基因分析.结果 在100份标本中检出8个HLA-DPA1等位基因和19个HLA-DPB1等位基因.HLA-DPA1等位基因频率较高的依次为DPA1*020202(47.0%)、DPA1*010301(38.5%)和DPA1*020101(10.5%).HLA-DPB1等位基因中,频率较高的依次为DPB1*0501(39.5%)、DPB1*020102(13.5%)和DPB1*040101(13.0%).连锁分析发现共有44个HLA-DPA1-DPB1单倍型,单倍型频率最高为DPA1*020202-DPB1*0501(29.5%).结论 浙江地区汉族人群HLA-DPA1和DPB1基因座等位基因具有丰富的多态性,2个基因座呈现连锁不平衡.     

广东汉族人群HLA-B基因多态性研究

目的调查广东汉族人群HLA-B位点基因多态性，比较不同人群HLA—B等位基因频率分布特征。方法应用测序技术测定562名广东汉族人HLA-B位点第2、3、4外显子序列，比对数据库得到分型结果，计算HLA-B等位基因频率并与不同人群进行比较。结果共检测到59种HLA-B等位基因，其中6种等位基因频率≥5％，分别是HLA-B＊4601（14．5％），HLA-B＊400101（14．4％），HLA—B＊1502（11．5％），HLA—B＊1301（8．6％），HLA-B＊5801（8．1％）和HLA-B＊380201（6．4％）。这6种等位基因的等位基因频率合计为63．5％。同时，检测到30种等位基因频率〈0．5％的HLA-B等位基因，这30种等位基因的等位基因频率合计为4．9％。广东汉族人群HLA-B等位基因频率总体分布与中国香港华人、新加坡华人比较差异无统计学意义（P〉0．05），但与日本人比较差异有统计学意义。结论分析了HLA-B基因在广东汉族人群中的分布特征，提供了较完整的HLA-B等位基因频率分布资料，为遗传学及疾病相关性等研究提供了重要的参考数据。     

华北汉族人群HLA单倍型研究

对北京附近河北省固安县地区的１０３个多子女家庭进行了ＨＬＡ－Ａ、Ｂ、Ｃ、ＤＲ、Ｂｆ、Ｃ２、Ｃ４Ａ、和Ｃ４Ｂ等八个位点的等位基因的分型，分析了八个位点的ＨＬＡ扩展单倍型，揭示出中国华北地区汉族人群ＨＬＡ单倍型的面貌。研究证明ＨＬＡ单倍型各位点间的等位基因呈高度的连锁不平衡，并显示出中国人不同于其他人种的特点。同时讨论了ＨＬＡ单倍型分析的重要意义。     

藏族人群的HLA多态性研究

藏族人群的ＨＬＡ多态性研究孙成文，孔繁华，金荔，陈兴国，张蕊芳人类白细胞抗原（ＨＬＡ）是迄今所知最复杂的遗传多态性系统，受控于第６对染色体短臂上一组紧密连锁的基因群。它不仅在免疫调控过程中发挥重要作用，而且其表现型随种族、地区等的不同而有所差异。１０...     

应用SBT直接测序分型法研究中国南方汉族人群HLA五个基因座单倍型

目的 研究中国南方汉族人群HLA-A、B、Cw、DRBl、DQBl等位基因多态性及单倍型的分布特征.方法 应用聚合酶链反应-直接测序分型(polymerase chain reaction sequence-based typing,PCR-SBT)法对186名中国南方汉族健康人群HLA-A、B、Cw、DRBl、DQBl进行基因分型.结果 检出的HLA-A、B、Cw、DRBl、DQBl等位基因分别有28、49、24、29、20种.经统计分析A*0207-B*4601(10.81%),A*3303-B*5801(6.14%),B*4601-DRBl*0901(6.22%),B*4001*DRBl*0901(3.78%),DRBl*0901-DQBl*0303(12.16%)和DRBl*1202-DQBl*0301(8.38%)单倍型呈强连锁不平衡单倍型(RLF≥0.5,X<'2>>3.84,P<0.05);A*0207-B*4601-Cw*0102(10.75%),A*3303-B*5801-Cw*0302(5.14%),A*0207-B*4601-DR*0901(5.07%),A*3303-B*5801-DRBl*0301(2.96%),A*0207-B*4601-Cw*0102-DRBl*0901-DQBl*0303(4.87%)和A*1101-B*1301-Cw*0304-DRBl*1501-DQBl*0601(2.43%)单倍型分别是中国南方汉族人群常见单倍型.结论 中国南方汉族人群HLA 5个基因座单倍型分布具有高度的遗传多态性且有其自身分布特点.本研究获得的较完整的HLA 5个基因座单倍型分布数据,将为人类学、HLA疾病相关性和器官移植等研究提供遗传学参考数据.     

HLA-Cw在广东汉族人群中的分布频率及其意义的初步分析

目的 :检测HLA Cw在广东汉族人群的分布频率 ,初步分析该人群中KIR与HLA Cw之间识别方式的特点及意义。方法 :骨髓移植供者 12 2例 ,ACD抗凝血提取DNA ,半量全自动PCR RSSO分型检测Cw。结果 :广东汉族人群HLA Cw基因频率分布由高至低依次为 :Cw 0 3(0 2 371) >Cw 0 7(0 2 15 9) >Cw 0 1(0 175 2 ) >Cw 0 8(0 112 9) >Cw 0 4 (0 0 5 0 5 ) >Cw 14、15(0 0 4 19) >Cw 12 (0 0 376 ) >Cw 0 6 (0 0 333) >Cw 0 5 (0 0 0 82 ) >Cw 16 (0 0 0 4 1)。第一组Cw 0 2 ,0 4 ,0 5 ,0 6识别KIR分子中2DL 2DSI;第二组Cw 0 1,0 3,0 7,0 8识别KIR分子中 2DL2 2DL3;2DS2 2DS3。两组分布频率相比有显著性差异 (P <0 0 1)。结论 :广东汉族人群HLA Cw 0 1,0 3,0 7,0 8出现频率较高 ,其与KIR的识别方式均属第二组。     

中国北方汉族HLA基因C位点遗传多态性研究

目的：研究北方汉族人群HLA(人类白细胞抗原)基因c位点的遗传特征。方法：采用序列特异性引物扩增(Polymerase Chain Reaction-Sequence-Specific Primers PCR-SSP)方法对205个样本进行HLA-C及-A、-B基因特异性分析。结果：检出C位点特异性14个，其中Cw*01、*07基因表现频率最高，分别为30．73％和27．80％；血清学方法检测不出的HLA-Cw*12、*14、*15表现频率分别为13．17％、4．88％、8．78％。统计显示显著性连锁不平衡的HLA-B-C单倍型24个，HLAs-A-C单倍型5个。结论：作为中国北方人HLA遗传多态性群体调查，提供了一套比较完整准确的基因频率和连锁不平衡参数，为人类学及疾病相关性等研究提供了较为完整的正常参考数据。     

广东汉族79例中iKIR及其HLA配体表达的初步分析

目的　探索杀伤细胞免疫球蛋白样抑制性受体 (iKIR)及其人白细胞抗原 (HLA)配体在中国广东汉族人群中的分布。方法　对 79例广东汉族人 ,采用引物序列特异性扩增法检测其iKIR表型 ,HLA A、B、Cw表型。HLA A、B分型采用BiotestHLA分型 (SSP)试剂盒 ,HLA C分型采用半量全自动PCR SSO分型。结果　KIR2DL1、2DL2、2DL3、2DL4、2DL5、3DL1、3DL2、3DL3的表型频率分别为0 .87、0 .13、0 .5 2、1、0 .18、0 .94、1和 0 .99。个体 86 .1%表达 1种以上iKIR HLA配对 ,其中 3DL1 HLA Bw4配对表型频率为 6 9.6 % ,2DL2 C2为 4 3.0 % ,2DL1 C1为 16 .5 %。由于不表达HLA A3,该组人群中无 3DL2 HLA A3受体配体对。 13.9%人群缺乏iKIR HLA配对。结论　约 7/ 8的广东汉族个体表达1种以上iKIR HLA配对 ,以 3DL1 HLA Bw4配对为主 ;约 1/ 8个体缺乏已知的iKIR HLA配对。     

广东汉族人群HLA Ⅰ、Ⅱ基因多态性及单倍型分析

目的 检测广东汉族人群HLA-A、B、Cw、DRB1基因频率，分析该人群HLAⅠ、Ⅱ等位基因多态性及其单倍型特点。方法 骨髓移植供者160人，抗凝血提取DNA，半量全自动聚合酶链反应-单链构象多态分型检测HLA-A、B、Cw、DRB1基因型。结果 在低分辨水平分别检出HLA-A、B、Cw及DRB1等位基因12、23、11、13个。统计分析呈现显著连锁不平衡的HLA-A-B单倍型9个，B-Cw单倍型20个，A-Cw单倍型7个，HLA-A-DRB1单倍型8个，B-DRB1单倍型9个，Cw-DRB1单倍型10个。结论 广东汉族群体HLA-基因具有较为丰富的多态性，其双座位连锁不平衡单倍型具有地区性遗传特征。     

中国广东地区汉族人群补体C4单倍型分析

采用改良的国际补体参考实验室方法,检测广东地区汉族人群补体C4单倍型。在156条无关染色体中,共检出14种C4单倍型:A3B1频率最高(0.3269),A3B2(0.2436)和A4B2(0.1090)次之,以下依次为A4B1(0.0705);AQ0B2和AQ0B1(均为0.0641);A2B1(0.0321);A3BQ0(0.0256);A3B5和A3B4(均为0.0192);A5B4、AQ0B4、AQ0B96和AQ0BQ0频率最低(均为0.0064)。其中A4B2和A2B1呈正向连锁不平衡。将广东汉族与其它不同种族群体的数据进行比较,发现广东汉族C4单倍型分布具有明显特点。     

HLA allele and haplotype frequencies in the Panamanian population

In this study, we report for the first time HLA allele and haplotype frequencies in the modern Panamanian population at a two-field (four digits) resolution level. Reported frequencies were calculated from genotype data for the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci of 462 healthy unrelated Panamanian adults of Hispanic ethnicity. In addition to providing new insights on the allelic structure of the Panamanian population and its origin, these data are critical for better planning of healthcare strategies in the country and for future research exploring the association with certain chronic and infectious diseases.     

Allele and eight-locus haplotype frequencies in population of Belgorod region,Russia

This paper reports the HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and –DPB1 alleles and estimated haplotype frequencies in a population of 153 healthy potential blood marrow donors from Belgorod region, Russia. HLA genotyping was performed by next generation sequencing method (NGS). Statistical analysis were performed using Arlequin software packages. There was no deviation from Hardy-Weinberg Equilibrium detected at HLA-A, -B, -DRB1, -DQA1, -DQB1, and -DPA1 loci. Deviation was detected at the HLA-C and DPB1 locus probably due to an excess of C*12:03:01 and DPB1*04:01:01 homozygotes. These genotype data are available in the Allele Frequencies Net Database under the population name, “Russia, Belgorod Region” and the identifier: 3780.     

中国湖北汉族人群对同种异型抗原免疫应答与HLA遗传多态性的相关性

目的研究个体之间混合淋巴细胞反应强度的差异,探讨中国汉族人群对同种异型抗原的应答水平与ＨＬＡ的相关性。方法在１７个家系中进行父／子和母／子间单向混合淋巴细胞培养。结果和结论不同组合的混合淋巴细胞反应强度,即父→子与子→父相比;母→子与子→母相比;父／子间与母／子间相比,差异均无显著性。个体对同种异型抗原的免疫应答的强度与ＨＬＡ－Ⅰ类分子的型别相关,ＨＬＡ－Ａ１０表型阳性个体的刺激指数ＳＩ（０．９５±０．２４）明显低于阴性个体（１．４１±０．６９）,差异具有极显著性意义。     

Next-Generation Sequencing of the HLA locus: Methods and impacts on HLA typing,population genetics and disease association studies

The human Major Histocompatibility Complex, known as the “Human Leukocyte Antigen (HLA)”, could be defined as a “super locus” (historically called “supergene”) governing the adaptive immune system in vertebrates. It also harbors genes involved in innate immunity. HLA is the most gene-dense, polymorphic and disease-associated region of the human genome. It is of critical medical relevance given its involvement in the fate of the transplanted organs/tissues and its association with more than 100 diseases. However, despite these important roles, comprehensive sequence analysis of the 4 megabase HLA locus has been limited due to technological challenges. Thanks to recent improvements in Next-Generation Sequencing (NGS) technologies however, one is now able to handle the peculiarities of the MHC notably the tight linkage disequilibrium between genes as well as their high degree of polymorphism (and hence heterozygosity). Increased read lengths, throughput, accuracy, as well as development of new bioinformatics tools now enable to efficiently generate complete and accurate full-length HLA haplotypes without phase ambiguities. The present report reviews current NGS approaches to capture, sequence and analyze HLA genes and loci. The impact of these new methodologies on various applications including HLA typing, population genetics and disease association studies are discussed.     

HLA class II haplotypes in Mexican systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is an autoimmune disease in which polymorphisms within the human leukocyte antigen (HLA) region have been associated to its etiology. For this study, HLA-DQB1, DQA1, and DRB1 genes were typed by polymerase chain reaction–sequence-specific primer in 237 individuals, taken from 74 families, who had a member with SLE, and who had their residence in the western region of Mexico; as well as in 159 ethnically matched healthy volunteers taken from 32 families. Genotype and allele frequency analysis was performed in 74 SLE patients and 54 unrelated controls. Precise three-loci identification of independent haplotypes was performed in 48 patients and 54 controls by familial segregation. Genotype distribution at each loci was concordant with Hardy-Weinberg’s equilibrium in the control group. In general, no genotype effect was observed in SLE patients. Allele distribution comparison showed in the SLE group a significant increase of HLA-DQA1*0102, DQB1*0402, and DRB1*15; whereas alleles HLA-DQB1*0303 and *0501 were significantly decreased. SLE patients showed haplotype DQB1*0602-DQA1-*0102-DRB1*15 increased. As expected, patients with SLE have a reduced haplotype genetic diversity. The associations found in this study are related to an ancestral haplotype that has been observed in SLE populations of different origins.     

湖北汉族人群对乙肝疫苗免疫应答的水平与HLA-I类分子多态性的相关研究

目的：探讨人群对乙肝疫苗免疫应答与ＨＬＡ遗传多态性的相关性。方法：对５２名湖北汉族健康自愿者进行ＨＢＶ血源疫苗标准全程接种,共３次（第０、１、６月）,末次接种后８ｗ用酶免疫法（ＥＩＡ）检测血清抗ＨＢｓ抗体水平：Ｓ／Ｎ≥２１为应答者;Ｓ／Ｎ＜２１为无应答者。同时对受试者进行ＨＬＡＩ类抗原多态性检测。结果：应答者４２人（８１０％）,无应答者１０人（１９０％）;无应答者与ＨＬＡＢ３９具有显著相关性,ＲＲ＝１７５,χ２＝５２２,Ｐ＜００５,而与ＨＬＡＢ６２呈负相关,χ２＝６４１,Ｐ＜００５。结论：在湖北汉族人群中,ＨＬＡＢ３９表型阳性个体对乙肝疫苗免疫应答水平明显低于其他个体,而ＨＬＡＢ６２表型阳性个体明显高于其他个体。