title: SNP profile within the human major histocompatibility complex reveals an extreme and interrupted level of nucleotide diversity.
abstract: The human major histocompatibility complex (MHC) is characterized by polymorphic multicopy gene families, such as HLA and MIC (PERB11); duplications; insertions and deletions (indels); and uneven rates of recombination. Polymorphisms at the antigen recognition sites of the HLA class I and II genes and at associated neutral sites have been attributed to balancing selection and a hitchhiking effect, respectively. We, and others, have previously shown that nucleotide diversity between MHC haplotypes at non-HLA sites is unusually high (>10%) and up to several times greater than elsewhere in the genome (0.08%-0.2%). We report here the most extensive analysis of nucleotide diversity within a continuous sequence in the genome. We constructed a single nucleotide polymorphism (SNP) profile that reveals a pattern of extreme but interrupted levels of nucleotide diversity by comparing a continuous sequence within haplotypes in three genomic subregions of the MHC. A comparison of several haplotypes within one of the genomic subregions containing the HLA-B and -C loci suggests that positive selection is operating over the whole subgenomic region, including HLA and non-HLA genes. [The sequence data for the multiple haplotype comparisons within the class I region have been submitted to DDBJ/EMBL/GenBank under accession nos. AF029061, AF029062, and AB031005-AB031010. Additional sequence data have been submitted to the DDBJ data library under accession nos. AB031005-AB03101 and AF029061-AF029062.]
authors.affiliation: Center for Information Biology, National Institute of Genetics, Mishima, Shizuoka-ken 411-8540, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Gaudieri
authors.forename: R L
authors.initials: RL
authors.lastname: Dawkins
authors.forename: K
authors.initials: K
authors.lastname: Habara
authors.forename: J K
authors.initials: JK
authors.lastname: Kulski
authors.forename: T
authors.initials: T
authors.lastname: Gojobori
mesh_terms: D001482:Base Composition / Q000235:genetics; D002460:Cell Line; D019295:Computational Biology; D019143:Evolution, Molecular; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D006680:HLA Antigens; D009711:Nucleotides