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鉴定一个越南起源的食蟹猕猴群体中的 MHC Mafa-DRB 等位基因。

Identification of MhcMafa-DRB alleles in a cohort of cynomolgus macaques of Vietnamese origin.

机构信息

School of Life Science, General Hospital of PLA T, Beijing, PR China.

出版信息

Am J Primatol. 2012 Oct;74(10):958-66. doi: 10.1002/ajp.22048. Epub 2012 Jul 2.

Abstract

Cynomolgus macaques have been used widely to build a research model of infectious and chronic diseases, as well as in transplantation studies, where disease susceptibility and/or resistance are associated with the major histocompatibility complex (MHC). To better elucidate polymorphisms and genetic differences in the Mafa-DRB locus, and facilitate the experimental use of cynomolgus macaques, we used pool screening combined with cloning and direct sequencing of polymerase chain reaction products to characterize MhcMafa-DRB gene alleles in 153 Vietnamese cynomolgus macaques. We identified 30 Mafa-DRB alleles belonging to 17 allelic lineages, including four novel sequences that had not been documented in earlier reports. The highest frequency allele was Mafa-DRBW27:04, which was present in 7 of 35 (20%) monkeys. The next most frequent alleles were Mafa-DRB3:07 and Mafa-DRBW7:01, which were detected in 5 of 35 (14.3%) and 4 of 35 (11.4%) of the monkeys, respectively. The high-frequency alleles in this Vietnamese population may be high priority targets for additional characterization of immune functions. Only the DRB103 and DRB1*10 lineages were also present in humans, whereas the remaining alleles were monkey-specific lineages. We found 25 variable sites by aligning the deduced amino acid sequences of 29 identified alleles. Evolutionary and population analyses based on these sequences showed that human, rhesus, and cynomolgus macaques share several Mhc-DRB lineages and the shared polymorphisms in the DRB region may be attributable to the existence of interbreeding between rhesus and cynomolgus macaques. This information will promote the understanding of MHC diversity and polymorphism in cynomolgus macaques and increase the value of this species as a model for biomedical research.

摘要

食蟹猴被广泛用于建立传染性和慢性疾病的研究模型,以及移植研究,其中疾病易感性和/或抗性与主要组织相容性复合体 (MHC) 有关。为了更好地阐明 Mafa-DRB 基因座的多态性和遗传差异,并促进食蟹猴的实验应用,我们使用池筛选结合聚合酶链反应产物的克隆和直接测序,对 153 只越南食蟹猴的 MHC Mafa-DRB 基因等位基因进行了特征分析。我们确定了 30 个 Mafa-DRB 等位基因,属于 17 个等位基因谱系,其中包括 4 个在早期报道中未记录的新序列。频率最高的等位基因是 Mafa-DRBW27:04,在 35 只猴子中的 7 只(20%)中存在。其次是 Mafa-DRB3:07 和 Mafa-DRBW7:01,在 35 只猴子中的 5 只(14.3%)和 4 只(11.4%)中检测到。在这个越南人群中,高频等位基因可能是进一步表征免疫功能的高优先级目标。仅 DRB103 和 DRB1*10 谱系也存在于人类中,而其余等位基因是猴子特异性的谱系。通过对齐 29 个鉴定出的等位基因的推导氨基酸序列,我们发现了 25 个可变位点。基于这些序列的进化和群体分析表明,人类、恒河猴和食蟹猴共享几个 MHC-DRB 谱系,DRB 区域的共享多态性可能归因于恒河猴和食蟹猴之间的杂交。这些信息将促进对食蟹猴 MHC 多样性和多态性的理解,并提高该物种作为生物医学研究模型的价值。

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