一种罕见的人类白细胞抗原HLA-B/Cw座位间的基因重组  

An unusual recombination event occurring between HLA-B and -Cw loci within a Chinese Han family

作　　者：骆媛[1] 孙玉英[1] 金荔[1] 梁飞[1] 刘楠[1] 宋新强[1] 袁方[1] 刘曙光[1] 刘金锋[1] 奚永志[1] 

机构地区：[1]军事医学科学院附属医院免疫学研究室及国家生物医学分析中心免疫学研究室,北京100071

出　　处：《中华医学杂志》2006年第9期628-631,共4页National Medical Journal of China

基　　金：国家"973"重大基础研究基金资助项目(2003CB515509);国家自然科学基金资助项目(30470751)

摘　　要：目的探讨人类白细胞抗原复合体HLA-B/C座位间的基因重组。方法采集拟进行造血干细胞移植的一例患者(男,39岁)及其妻女的外周血标本,首先对其HLA-Ⅰ、Ⅱ类区域的5个经典基因位点进行顺序特异引物PCR(PCR-SSP)低、高分辨基因分型及SBT分析,然后再进行遗传家系分析研究,确定HLA基因重组相关位点。结果HLA高分辨基因分型的结果证实患者(AML-M5患者)的2条单倍型分别为A2402101-Cw030401/0402-B1301-DRB10406-DQB1030302/0303与A02011-Cw150201/0202-B4002-DRB11405-DQB105031;其女儿的2条单倍型分别为A02011-Cw150201/0202-B1301-DRB10406-DQB1030302/0303与A2406-Cw0602-B1302-DRB1070101/0102-DQB10202;患者配偶的2条单倍型则分别为A330301/0302-Cw030201/0202-B5801-DRB117-DQB10202与A2406-Cw0602-B1302-DRB1070101/0102-DQB10202。从遗传家系分析显示,患者的女儿所携有的父源A02011-Cw150201/0202是源自父亲的一条染色单体,而B1301-DRB10406-DQB1030302/0303则源自父亲的另一条染色单体,这表明父亲的2条染色单体在减数分裂时HLA-B和-Cw基因座位间发生了重组,即2条染色体间发生了交换,重组后的单倍型又完整地遗传给了女儿。结论首次在国际上发现并证明了一例罕见的中国汉族人群HLA-B/C基因座位间的基因重组家系,这为更深入的研究HLA重组机制奠定了坚实基础。Objective To investigate the recombination event occurring between HLA-B and -Cw loci discovered in a family of Chinese Han nationality with an acute myeloid leukemia （AML） patient. Methods Peripheral blood samples were collected from a Chinese man with M5 type AML, aged 39, and his healthy wife and daughter, all of Han nationality. HLA class Ⅰ （-A, -B, and -Cw） and Ⅱ （-DRB1 and -DQB1 ） alleles were typed by both low and high resolution PCR with sequence specific primers （ PCR- SSP） and sequence-based typing （SBT）. Then the recombination sites were analyzed by family study. Results The 2 haplotypes of the patient, his daughter, and his wife were A ＊ 2402101-Cw ＊ 030401/0402- B ＊ 1301-DRB1 ＊ 0406-DQR1 ＊ 030302/0303 and A ＊ 02011-Cw ＊ 150201/0202-B ＊ 4002-DRB1 ＊ 1405- DQB1 ＊ 05031, A ＊ 02011-Cw ＊ 150201/0202-B ＊ 1301-DRB1 ＊ 0406-DQB1 ＊ 030302/0303 and A ＊ 2406-Cw ＊ 0602-B ＊ 1302_DRB1 ＊ 070101/0102-DQB1 ＊ 0202, and A ＊ 330301/0302-Cw ＊ 030201/0202- B ＊ 58-1-DRB1 ＊ 17-DQB1 ＊ 0202 and A ＊ 2406-Cw ＊ 0602-B ＊ 1302-DRB1 ＊ 070101/0102-B ＊ 5801- DRB1 ＊ 0202 respectively. Family study demonstrated that A ＊ 02011-Cw ＊ 150201/0202 recombination and B ＊ 1301-DRB1 ＊ 030302/0303 recombination carried by the daughter came from the 2 isolated chromosomes of her father, indicating that the recombination event occurred between HLA-B and -Cw loci during meiosis of the father and resulted in a new HLA haplotype that was inherited by the daughter. Conclusion An unusual HLA-B/Cw recombination event occurring between HLA-B and -Cw loci has been found in a Han family, which helps further study the mechanisms of HLA recombination.

关 键 词：人白细胞抗原 重组 遗传 

分 类 号：R392[医药卫生—免疫学]