title: Genomic organisation and allelic diversity within coding and non-coding regions of the Ovar-DRB1 locus.
abstract: In all but the most primitive vertebrates, multiple polymorphic genes associated with lymphocyte-mediated immunological surveillance are linked together within genomic regions termed the major histocompatibility complex (MHC). The extensive diversity at many MHC loci provides a valuable source of genetic markers for examining the complex relationships between host genotype and disease resistance or susceptibility. Such studies in domestic sheep (Ovis aries) have generally focused on exon 2 of the polymorphic class II MHC DRB1 gene and its adjacent sequences. We have determined the complete genomic sequences of two Ovar-DRB1 alleles, which has allowed an analysis of diversity at coding, non-coding and promoter regions of this gene. On the basis of these sequences, oligonucleotide primers were designed for amplification of full-length Ovar-DRB1 transcripts and used to evaluate diversity within an MHC-defined resource flock maintained at the Moredun Institute. We describe nine novel full-length Ovar-DRB1 sequences along with an improved direct-sequencing method for analysis of the entire exon 2 region of the Ovar-DRB1 gene based on previously unknown intronic sequences. We discuss how these data provide evidence on the evolution of MHC DRB diversity in domestic sheep.
authors.affiliation: Moredun Research Institute, Midlothian, EH26 OPZ, UK. keith.ballingall@moredun.ac.uk
authors.forename: Keith T
authors.initials: KT
authors.lastname: Ballingall
authors.forename: Kathleen
authors.initials: K
authors.lastname: Fardoe
authors.forename: Declan J
authors.initials: DJ
authors.lastname: McKeever
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons / Q000235:genetics*; D014644:Genetic Variation; D016678:Genome; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012756:Sheep / Q000235:genetics*
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012333:RNA, Messenger