猕猴MHC-DPB1基因外显子2多态性研究
收稿日期: 2009-11-24
修回日期: 2010-03-06
网络出版日期: 2010-05-24
基金资助
教育部“长江学者和创新团队发展计划”创新团队项目(编号：IRT0848), 动物疫病与人类健康四川省重点实验室开放基金项目(编号： SZDSYS-200601)和四川省教育厅自然科学基金重点项目(编号：08ZA076)资助
Polymorphism of MHC-DPB1 gene exon 2 in rhesus macaques (Macaca mulatta)
Received date: 2009-11-24
Revised date: 2010-03-06
Online published: 2010-05-24
猕猴(Macaca mulatta)是最理想的医学实验灵长类动物, 且为国家二级保护动物。为了解中国猕猴主要组织相容复合体(Major histocompatibility complex, MHC)基因的遗传多态性背景, 为它们在生物医学研究中的应用及其遗传资源的保护提供一定的科学依据, 文章采用变性梯度凝胶电泳(Denaturing gradient gel electrophoresis, DGGE)和克隆测序技术分析了106个四川野生猕猴MHC-DPB1基因的exon 2, 共检测到21个Mamu-DPB1等位基因, 其中有15个为本研究中首次发现的新等位基因; 从整个大的猕猴群体(106个个体)来看, 等位基因频率最高的是Mamu-DPB1*30(0.1120); 单独从不同地理群体来看, 最高等位基因频率分别为: 小金-DPB1*30 (0.1120), 黑水-DPB1*04 (0.1702), 巴中-DPB1*32 (0.1613), 汉源-DPB1*30(0.1120), 九龙-DPB1*04(0.1139); 氨基酸序列比对发现, 猕猴Mamu-DPB1等位基因编码的氨基酸序列中, 有12个氨基酸残基变异位点表现出物种特异性, 其中有9个位于新发现的15个Mamu-DPB1等位基因氨基酸序列中; 不同物种来源的DPB1等位基因系统发生树表明, 猕猴与其近缘物种食蟹猴(Macaca fascicularis)的DPB1等位基因间存在着跨种多态(Trans-species polymorphism)现象。研究还表明, MHC-DPB1等位基因在中国猕猴群体和先前为主要研究对象的印度猕猴群体间具有较大的差异。
关键词： 猕猴; 主要组织相容复合体Ⅱ类; Mamu-DPB1基因; 多态性
徐怀亮，汪宴廷，程安春，姚永芳，倪庆永，曾文，毕风均，杨泽霞，陈孝跃 . 猕猴MHC-DPB1基因外显子2多态性研究[J]. 遗传, 2010 , 32(6) : 588 -598 . DOI: 10.3724/SP.J.1005.2010.00588
Rhesus macaque (Macaca mulatta) has long been used as an experimental model animal for biomedical research and was under the key state protection (class II) from Chinese government. In order to facilitate the use of Chinese rhesus macaques in biomedical research and their protection based on better understanding of the major mistocompability complex (MHC) genes in these macaques, the exon 2 of Mamu-DPB1 genes were determined in 106 wild rhesus macaques using DGGE, cloning and sequencing. A total of 21 Mamu-DPB1 alleles were obtained, of which 15 alleles were novel sequences that had not been documented previously. Mamu-DPB1*30 was the most frequent allele in the whole large population comprising all 106 rhesus macaque individuals (0.1120) and in Xiaojin population (0.1120), Mamu-DPB1*04 in Heishui (0.1702), -DPB1*32 in Bazhong (0.1613), -DPB1*30 in Hanyuan (0.1120), and -DPB1*04 in Jiulong (0.1139). The alignment of the amino acids sequences showed that 12 variable sites were species-specific, of which 9 sites occurred in the putative amino acids sequences of the 15 novel Mamu-DPB1 alleles. Trans-species polymorphism was observed on the phylogenetic tree based on the DPB1 alleles of rhesus macaques and cynomolgus (Macaca fascicularis). In addition, these results also demonstrated that significant genetic differentiation has occurred between Chinese and Indian rhesus macaque population.
[1] Lackner AA, Veazey RS. Current concepts in AIDS pathogenesis: insights from the SIV/macaque model. Annu Rev Med, 2007, 58(1): 461–476.
[2] Seggewiss R, Loré K, Guenaga FJ, Pittaluga S, Mattapallil J, Chow CK, Koup RA, Camphausen K, Nason MC, Meier-Schellersheim M, Donahue RE, Blazar BR, Dunbar CE, Douek DC. Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood, 2007, 110(1): 441–449.
[3] Vierboom MP, Jonker M, Tak PP, t Hart BA. Preclinical models of arthritic disease in non-human primates. Drug Discov Today, 2007, 12(7–8): 327–335.
[4] Smith DG. Genetic characterization of Indian-origin and Chinese-origin rhesus macaques (Macaca mulatta). Comp Med, 2005, 55(3): 227–230.
[5] Boyson JE, Shufflebotham C, Cadavid LF, Urvater JA, Knapp LA, Hughes AL, Watkins DI. The MHC class I genes of the rhesus monkey: Different evolutionary histo-ries of MHC class I and II genes in primates. J Immunol, 1996, 156(12): 4656–4665.
[6] Jones EY, Fugger L, Strominger JL, Siebold C. MHC class II proteins and disease: a structural perspective. Nat Rev Immunol, 2006, 6(4): 271–282.
[7] Rocha N, Neefjes J. MHC class II molecules on the move for successful antigen presentation. EMBO J, 2008, 27(1): 1–5.
[8] 季芳, 饶军华, 刘晓明. 恒河猴主要组织相容性复合体(MHC)的多态性研究概述. 中国比较医学杂志, 2007, 17(7): 420–425.
[9] 陈瑾, 代解杰, 和占龙, 李琦涵, 杨贵波, 孙晓梅. 云南地区恒河猴MHC部分基因频率及多态性的分析. 中国实验动物学报, 2008, 12(6): 410–416.
[10] Doxiadis GG, Otting N, de Groot NG, Bontrop RE. Dif-ferential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies. Immunol Rev, 2001, 183(1): 76–85.
[11] Doxiadis GG, Otting N, de Groot NG, de Groot N, Rou-weler AJ, Noort R, Verschoor EJ, Bontjer I, Bontrop RE. Evolutionary stability of MHC class II haplotypes in di-verse rhesus macaque populations. Immunogenetics, 2003, 55(8): 540–551.
[12] Qiu CL, Yang GB, Yu K, Li Y, Li XL, Liu Q, Zhao H, Xing H, Shao Y. Characterization of the major histocom-patibility complex class II DQB (MhcMamu-DQB1) alleles in a cohort of Chinese rhesus macaques (Macaca mulatta). Hum Immunol, 2008, 69(8): 513–521.
[13] McCanlies EC, Ensey JS, Schuler CR, Kreiss K, Weston A. The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization. Am J Ind Med, 2004, 46(2): 95–103.
[14] Slierendregt BL, Otting N, Kenter M, Bontrop RE. Allelic diversity at the Mhc-DP locus in rhesus macaques (Macaca mulatta). Immunogenetics, 1995, 41(1): 29–37.
[15] Arnold ML, Pei R, Spriewald B, Wassmuth R. Anti-HLA class II antibodies in kidney retransplant patients. Tissue Antigens, 2005, 65(4): 370–378.
[16] Ma X, Tang LH, Qu LB, Ma J, Chen L. Identification of 17 novel major histocompatibility complex-A alleles in a population of Chinese-origin rhesus macaques. Tissue Antigens, 2009, 73(2): 184–187.
[17] Ouyang D, Xu L, Dai Z, Shi H, Zhang G, Zheng Y, He X. Identification of major histocompatibility complex class I alleles in Chinese rhesus macaques. Acta Biochim Bio-phys Sin (Shanghai), 2008, 40(11): 919–927.
[18] Blasky AJ, Karl JA, Wiseman RW, Read DS, O'Connor DH. Rapid high-resolution MHC class I genotyping of Chinese rhesus macaques by capillary reference strand- mediated conformational analysis. Immunogenetics, 2008, 60(10): 575–584.
[19] Otting N, Heijmans CM, van der Wiel M, de Groot NG, Doxiadis GG, Bontrop RE. A snapshot of the Mamu-B genes and their allelic repertoire in rhesus macaques of Chinese origin. Immunogenetics, 2008, 60(9): 507–514
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:
