广东汉族HLA-A、C、B、DRB1和DQB1基因的高分辨多态性及连锁不平衡分析  

Polymorphism and linkage disequilibrium analysis of HLA-A,-C,-B,-DRB1 and -DQB1 genes at high-resolution level in Chinese Han population from Guangdong province

作　　者：朱为刚[1] 金士正[1] 邹红岩[1] 李桢[1] 蓝欲晓[1] 鲍自谦[1] 王大明[1] 程曦[1] 程良红[1] 

机构地区：[1]深圳市血液中心深圳市输血医学研究所,广东深圳518035

出　　处：《中国输血杂志》2009年第12期983-990,共8页Chinese Journal of Blood Transfusion

基　　金：广东省科技计划项目(2005B36001079;2008B030301278);广东省医学科研基金资助项目(A2008622);深圳市科技计划项目(200802117)资助课题

摘　　要：目的研究广东汉族人群的人类白细胞抗原(HLA)-A、C、B、DRB1和DQB1基因的高分辨多态性和等位基因间的连锁不平衡关系。方法PCR-测序分型方法(sequence-based typing,SBT)对144名随机广东汉族造血干细胞捐献者的HLA-A、C、B、DRB1和DQB1基因进行序列分析,并采用PyPop软件计算等位基因频率、单体型频率和连锁不平衡参数。结果发现1个新等位基因HLA-Cw*0340;HLA-Ⅰ类基因中,A、C、B基因座分别检出27、24和54个等位基因,其中频率>0.05常见等位基因包括A*1101、A*2402、A*0207、A*0201、A*3303、A*0203、Cw*0102、Cw*0702、Cw*0304、Cw*0801、Cw*0302、B*4601、B*4001、B*1301、B*5801和B*1502;HLA-Ⅱ类基因中,总共观察到30个DRB1和15个DQB1等位基因,频率>0.05的常见等位基因见于DRB1*0901、DRB1*0301、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*1101、DRB1*1602,DQB1*0303、DQB1*0301、DQB1*0502、DQB1*0601、DQB1*0201、DQB1*0302和DQB1*0501;除A-DQB1最常见单体型为A*1101-DQB1*0301外,其它所有两座位单倍型以及A-C-B、A-B-DRB1和A-C-B-DRB1-DQB1扩展单体型的最常见型均由A*0207、Cw*0102、B*4601、DRB1*0901和DQB1*0303组合而成。任意2个HLA基因间均具有强的连锁不平衡,而21.99%—31.63%的有价值连锁不平衡单倍型具有统计学意义(χ2>3.84,P<0.05),其中频率≥0.01的有156条。结论获得了广东汉族人群HLA-A、B、C、DRB1和DQB1基因的等位基因和单体型多态性及连锁不平衡分析数据,为HLA基因的相关研究和应用提供了更加详细的参考资料。Objective To study the polymorphism and （analysis） analyze the linkage disequilibrium parameters of human leukocyte antigen （HL4）-A, C, B, DRB1 and DQB1 genes at high-resolution level in Chinese Han population from Guangdong province. Methods One hundred and forty-four randomly selected Chinese Han hematopoietic stem cell donors from Guangdong province were genotyped by polymerase chain reaction （PCR） sequence-based-typing （SBT） method for their HLA-A, B, C, DRB1 and DQB1 genes, and then the allele frequencies, haplotype frequencies and the linkage disequilibrium parameters were computed by a PyPop software. Results A novel HLA-Cω^＊ 0340 allele was found in this population. For class Ⅰ HLA genes, there were twenty-seven, twenty-four and fifty-four alleles （were） observed in HLA-A, C and B locus respectively, and among them, the common alleles with frequencies higher than 0.05 were A^ ＊ 1101, A ^＊ 2402, A^＊0207, A^＊0201, A^＊3303, A^＊0203, Cω^＊0102, Cω^＊0702, Cω^＊0304, Cω^＊0801, Cω^＊0302, B^＊4601, B^＊4001, B^＊ 1301, B^＊5801 and B^＊ 1502. For class ⅡHLA genes, thirty DRB1 alleles and fifteen DQB1 alleles were observed and the frequent alleles with frequencies greater than 0. 05 included DRB1^＊ 0901, DRB1 ^＊ 0301, DRB1 ^＊ 1501, DRB1 ^＊ 1202, DRB1^＊0803, DRB1^＊ 1101, DRB1^＊ 1602, DQB1^＊0303, DQB1^＊0301, DQB1^＊0502, DQB1^＊ 0601, DQB1^＊0201, DQB1^＊0302 and DQB1^＊ 0501. The most frequent haplotypes were all constructed by the combination of according alleles which included A ^＊ 0207, Cω^＊0102, B^＊ 4601, DRB1^＊ 0901 and DQB1 ^＊ 0303 for all two-loci HLA haplotypes and three kind extended HLA haplotypes （A-C-B, A-B-DRB1 and A-C-B-DRB1-DQB1 ）, except that the A-DQB1 haplotype was A ^＊1101-DQB1^＊ 0301. Strong linkage disequilibrium was observed between in any two HLA genes. The ratio of informative linkage disequilibrium haplotyptes with statistically significant ranged from 21.99% to 31.63% （ χ^2 〉 3.84, P 〈

关 键 词：人类白细胞抗原 HLA等位基因 单体型 连锁不平衡 汉族 广东 

分 类 号：R457.11[医药卫生—治疗学]