Macaques provide the most widely used nonhuman primate models for studying the immunology and pathogenesis of human diseases. Although the macaque major histocompatibility complex (MHC) region shares most features with the human leukocyte antigen (HLA) region, macaques have an expanded repertoire of MHC class I genes. Although a chimera of two rhesus macaque MHC haplotypes was first published in 2004, the structural diversity of MHC genomic organization in macaques remains poorly understood owing to a lack of adequate genomic reference sequences. We used ultralong Oxford Nanopore and high-accuracy Pacific Biosciences (PacBio) HiFi sequences to fully assemble the ∼5.2-Mb M3 haplotype of an MHC-homozygous, Mauritian-origin cynomolgus macaque (Macaca fascicularis). The MHC homozygosity allowed us to assemble a single MHC haplotype unambiguously and avoid chimeric assemblies that hampered previous efforts to characterize this exceptionally complex genomic region in macaques. The high quality of this new assembly is exemplified by the identification of an extended cluster of six Mafa-AG genes that contains a recent duplication with a highly similar ∼48.5-kb block of sequence. The MHC class II region of this M3 haplotype is similar to the previously sequenced rhesus macaque haplotype and HLA class II haplotypes. The MHC class I region, in contrast, contains 13 MHC-B genes, four MHC-A genes, and three MHC-E genes (vs. 19 MHC-B, two MHC-A, and one MHC-E in the previously sequenced haplotype). These results provide an unambiguously assembled single contiguous cynomolgus macaque MHC haplotype with fully curated gene annotations that will inform infectious disease and transplantation research.

中文翻译：

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食蟹猴主要组织相容性复合体单倍型的完整测序

猕猴为研究人类疾病的免疫学和发病机制提供了最广泛使用的非人灵长类动物模型。尽管猕猴主要组织相容性复合体 (MHC) 区域与人类白细胞抗原 (HLA) 区域具有大部分特征，但猕猴拥有更多的 MHC I 类基因。尽管两种恒河猴 MHC 单倍型的嵌合体于 2004 年首次发表，但由于缺乏足够的基因组参考序列，人们对猕猴 MHC 基因组组织的结构多样性仍然知之甚少。我们使用超长 Oxford Nanopore 和高精度 Pacific Biosciences (PacBio) HiFi 序列来完全组装 MHC 纯合毛里求斯食蟹猴 (Macaca fascicularis) 的~5.2-Mb M3 单倍型。MHC 纯合性使我们能够明确地组装单个 MHC 单倍型，并避免嵌合组装，嵌合组装阻碍了先前表征猕猴中这一异常复杂的基因组区域的努力。这种新组装的高质量通过六个Mafa-AG基因的扩展簇的鉴定得到了例证，该簇包含最近的重复，具有高度相似的 ~48.5-kb 序列块。该M3单倍型的MHC II类区域与先前测序的恒河猴单倍型和HLA II类单倍型相似。相比之下，MHC I 类区域包含 13 个MHC - B基因、4 个MHC - A基因和 3 个MHC - E基因（之前测序的序列中包含 19 个MHC - B基因、2 个MHC - A基因和 1 个MHC - E基因）单倍型）。这些结果提供了一个明确组装的单个连续食蟹猴 MHC 单倍型，具有完全策划的基因注释，将为传染病和移植研究提供信息。