title: Complex MHC Class I Gene Transcription Profiles and Their Functional Impact in Orangutans.
abstract: MHC haplotypes of humans and the African great ape species have one copy of the MHC-A, -B, and -C genes. In contrast, MHC haplotypes of orangutans, the Asian great ape species, exhibit variation in the number of gene copies. An in-depth analysis of the MHC class I gene repertoire in the two orangutan species, Pongo abelii and Pongo pygmaeus, is presented in this article. This analysis involved Sanger and next-generation sequencing methodologies, revealing diverse and complicated transcription profiles for orangutan MHC-A, -B, and -C. Thirty-five previously unreported MHC class I alleles are described. The data demonstrate that each orangutan MHC haplotype has one copy of the MHC-A gene, and that the MHC-B region has been subject to duplication, giving rise to at least three MHC-B genes. The MHC-B*03 and -B*08 lineages of alleles each account for a separate MHC-B gene. All MHC-B*08 allotypes have the C1-epitope motif recognized by killer cell Ig-like receptor. At least one other MHC-B gene is present, pointing to MHC-B alleles that are not B*03 or B*08. The MHC-C gene is present only on some haplotypes, and each MHC-C allotype has the C1-epitope. The transcription profiles demonstrate that MHC-A alleles are highly transcribed, whereas MHC-C alleles, when present, are transcribed at very low levels. The MHC-B alleles are transcribed to a variable extent and over a wide range. For those orangutan MHC class I allotypes that are detected by human monoclonal anti-HLA class I Abs, the level of cell-surface expression of proteins correlates with the level of transcription of the allele.
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands; groot@bprc.nl.
authors.forename: Natasja G
authors.initials: NG
authors.lastname: de Groot
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands;
authors.forename: Corrine M C
authors.initials: CM
authors.lastname: Heijmans
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands;
authors.forename: Marit K H
authors.initials: MK
authors.lastname: van der Wiel
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Jeroen H
authors.initials: JH
authors.lastname: Blokhuis
authors.affiliation: Immunohaematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; and.
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands;
authors.forename: Gaby G M
authors.initials: GG
authors.lastname: Doxiadis
authors.affiliation: Immunohaematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; and.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.affiliation: Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands; Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Bontrop
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D005805:Genes, MHC Class I; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010802:Phylogeny; D057080:Pongo abelii / Q000235:genetics*; D011148:Pongo pygmaeus / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome