title: Identification of two pseudogenes with sequence homology to human and gorilla MHC class IA genes: ancestral haplotype in the Filipino population.
abstract: While characterizing exons 2 and 3 of the class I human leukocyte antigen (HLA)-A locus in human lymphocytes, two similar but unexpected PCR products were detected in six samples of Filipino ethnicity. A nucleotide sequence analysis of the two amplicons, tentatively named HLA-COQ and HLA-DEL, rendered them as two novel and seemingly related sequences, both with homology to the gorilla and human major histocompatibility complex (MHC) A locus. Exon 2 is similar to the published human pseudogenes HLA-BEL, HLA-Y, and to primate MHC Gogo-A*0501, differing by 2 bp from HLA-BEL, and HLA-Y, and by 4 bp from Gogo-A*0501. Exon 3 is most similar to HLA-A*2902 and A*310102, differing by 7 bp from A*2902, and by 8 bp from A*31012. Genomic sequence comparison of exons 1 to 8 indicates that their closest published match is to the Gogo-A*0501. Complete typing at the HLA-A, -B, -C, DRB1, and DRB5 loci for the six samples yielded the reoccurring types: HLA-A*3401, -B*1521/1525, -Cw*0403, -DRB1*150201, and DRB5*010101. Thus far, HLA-COQ and HLA-DEL have been detected only in Filipino samples containing these HLA types. The HLA-COQ gene is nonfunctional based on a stop codon located in exon 4. HLA-DEL is also a nonfunctional gene because of the dual cytosine insertion in exon 4, with a reading frame shift generating a stop codon downstream. Parsimony analysis of the two pseudogenes with 31 other primate A locus coding regions resulted in a phylogenetic tree that segregated the two pseudogenes with the Gogo-A*0501, suggesting that HLA-COQ, HLA-DEL, and Gogo-A*0501 evolved from a common ancestral allele.
authors.affiliation: Children's Memorial Hospital, Chicago, IL, USA. g-coquillard@northwestern.edu
authors.forename: G
authors.initials: G
authors.lastname: Coquillard
authors.forename: M
authors.initials: M
authors.lastname: Lau
authors.forename: M
authors.initials: M
authors.lastname: Kletzel
authors.forename: S G
authors.initials: SG
authors.lastname: Rodriguez-Marino
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons / Q000235:genetics* / Q000276:immunology; D016368:Frameshift Mutation / Q000235:genetics / Q000276:immunology; D006071:Gorilla gorilla / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010679:Philippines; D010802:Phylogeny; D011544:Pseudogenes / Q000235:genetics* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I