Study of MHC class II region polymorphism in the Filipino cynomolgus macaque population
Study of MHC class II region polymorphism in the Filipino cynomolgus macaque population
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DOI：
10.1007/s00251-014-0764-7
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发表时间：
2014-04-01
期刊：
影响因子：
3.2
通讯作者：
Shiina, T.
中科院分区：
文献类型：
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作者：
Blancher, A.;Aarnink, A.;Shiina, T.
食蟹猴（Macaca fascicularis）目前在免疫学的各个领域中用作动物模型，特别是在用于预防和治疗传染病的创新疫苗的开发中。主要组织相容性复合体（MHC）的多态性影响适应性免疫反应的发展，表征食蟹猴MHC基因的多态性至关重要。在这里，我们提出了一个系统的研究菲律宾猕猴群体的MHC II类单倍型。通过对大样本菲律宾动物（N = 353）的研究，我们通过对7个微卫星进行基因分型，确定了18个MHC II类单倍型。通过对基因组扩增片段进行PCR-SSO或DGGE测序对动物进行DRB基因分型。我们克隆了117只动物的DQA、DQB、DPA和DPB基因的cDNA序列。结合微卫星基因分型和cDNA的特点，在117只动物，我们定义的cDNA和微卫星之间的遗传关联，并表征了18个MHC II类单倍型。对于研究的353只动物中的104只，重组单倍型的存在是高度可能的。34%的重组位于D 6S 2876和D 6S 2747微卫星之间的256 kb片段，该区域包含人MHC中的几个重组热点。
The cynomolgus macaque (Macaca fascicularis) is currently used as an animal model in various fields of immunology especially in the development of innovative vaccines for the prevention and treatment of infectious diseases. The polymorphism of the major histocompatibility complex (MHC) influences the development of adaptive immune responses and it is crucial to characterize the polymorphism of cynomolgus MHC genes. We present here a systematic study of the MHC class II haplotypes in the Filipino macaque population. By the study of a large sample of Filipino animals (N = 353), we have characterized 18 MHC class II haplotypes by means of genotyping seven microsatellites. The animals were DRB genotyped by means of PCR-SSO or DGGE-sequencing on genomic amplified fragments. We cloned and sequenced the complementary DNA (cDNA) of DQA, DQB, DPA, and DPB genes of 117 animals. Combining the microsatellite genotyping and cDNA characterized in the 117 animals, we defined genetic association between the cDNA and the microsatellites and characterized 18 MHC class II haplotypes. For 104 animals out of the 353 studied, the presence of a recombinant haplotype was highly probable. Thirty-four percent of recombination was located in 256 kb segment between D6S2876 and D6S2747 microsatellites, a region encompassing several hot spots of recombination in the human MHC.