PMID- 36854669 OWN - NLM STAT- MEDLINE DCOM- 20230615 LR - 20240215 IS - 1549-5469 (Electronic) IS - 1088-9051 (Print) IS - 1088-9051 (Linking) VI - 33 IP - 3 DP - 2023 Mar TI - Complete sequencing of a cynomolgus macaque major histocompatibility complex haplotype. PG - 448-462 LID - 10.1101/gr.277429.122 [doi] AB - 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 approximately 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 approximately 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. CI - (c) 2023 Karl et al.; Published by Cold Spring Harbor Laboratory Press. FAU - Karl, Julie A AU - Karl JA AUID- ORCID: 0000-0002-4447-4721 AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. FAU - Prall, Trent M AU - Prall TM AUID- ORCID: 0000-0003-0635-4152 AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. FAU - Bussan, Hailey E AU - Bussan HE AUID- ORCID: 0000-0002-0961-7109 AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. FAU - Varghese, Joshua M AU - Varghese JM AUID- ORCID: 0000-0001-9777-0818 AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. FAU - Pal, Aparna AU - Pal A AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. FAU - Wiseman, Roger W AU - Wiseman RW AUID- ORCID: 0000-0002-7682-7085 AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. AD - Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA. FAU - O'Connor, David H AU - O'Connor DH AUID- ORCID: 0000-0003-2139-470X AD - Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA; dhoconno@wisc.edu. AD - Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA. LA - eng GR - P51 OD011106/OD/NIH HHS/United States GR - T15 LM007359/LM/NLM NIH HHS/United States GR - T32 GM140935/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230228 PL - United States TA - Genome Res JT - Genome research JID - 9518021 SB - IM MH - Animals MH - Humans MH - Macaca fascicularis/genetics MH - Haplotypes MH - Macaca mulatta/genetics MH - *Major Histocompatibility Complex/genetics MH - Sequence Analysis, DNA/methods MH - Alleles PMC - PMC10078292 EDAT- 2023/03/01 06:00 MHDA- 2023/06/15 06:42 PMCR- 2023/09/01 CRDT- 2023/02/28 23:35 PHST- 2022/10/24 00:00 [received] PHST- 2023/02/21 00:00 [accepted] PHST- 2023/06/15 06:42 [medline] PHST- 2023/03/01 06:00 [pubmed] PHST- 2023/02/28 23:35 [entrez] PHST- 2023/09/01 00:00 [pmc-release] AID - gr.277429.122 [pii] AID - 10.1101/gr.277429.122 [doi] PST - ppublish SO - Genome Res. 2023 Mar;33(3):448-462. doi: 10.1101/gr.277429.122. Epub 2023 Feb 28.