Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.
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DOI:
10.1007/s00251-017-1042-2
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发表时间:
2018-06
期刊:
影响因子:
3.2
通讯作者:
O'Connor DH
O'Connor DH
中科院分区:
医学4区
文献类型:
--
作者:
Semler MR;Wiseman RW;Karl JA;Graham ME;Gieger SM;O'Connor DH

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猪尾猕猴(Macaca nomestrina,Mane)是研究人类免疫缺陷病毒(HIV)的重要模型。它们对最小修饰的艾滋病毒的感染性使它们成为模拟人类感染艾滋病毒并进展为获得性免疫缺陷综合征(艾滋病)的独特的有价值的动物模型。然而,与恒河猴和食蟹猴相比,猪尾猴主要组织相容性复合体(MHC)的变异以及单个转录本在HIV和其他传染病发病机制中的影响还没有得到充分的研究。在这项研究中,我们使用太平洋生物科学的单分子实时循环一致测序来描述来自三个繁育中心的194只猪尾猕猴的MHC-I类(MHC-I)转录本。然后,我们使用全长序列来推断Mane-A和Mane-B单倍型,这些单倍型包含由于物理连锁而共分离的MHC-I转录物组。总之,我们对313个Mane-A、Mane-B和Mane-I序列的全长开放读框(ORF)进行了表征,这些序列定义了86个Mane-A和106个Mane-B MHC-I单倍型。太平洋生物科学技术使我们能够将这些MANE-A和MANE-B单倍型解析到同义等位基因变体的水平。新定义的含有全长ORF的单倍型和转录本序列为传染病研究人员提供了重要的资源,因为某些MHC单倍型已被证明能够特殊控制猴免疫缺陷病毒(SIV)在非人类灵长类动物中的复制和预防艾滋病样疾病。太平洋生物科学测序提供的更高的等位基因分辨率也有利于移植研究,使研究人员能够更具体地将捐赠者和接受者之间的单倍型与非同义等位基因变异水平进行匹配,从而降低移植物抗宿主疾病的风险。
Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.
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期刊: G3 (Bethesda, Md.)
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发表时间: 2007-08-01
影响因子: 5.4
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DOI: 10.1007/s00251-009-0397-4
发表时间: 2009-10-01
期刊: IMMUNOGENETICS
影响因子: 3.2
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发表时间: 2009-03-17
影响因子: 11.1
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通讯作者: Bieniasz, Paul D.