title: Analysis of the genomic region containing the tammar wallaby (Macropus eugenii) orthologues of MHC class III genes.
abstract: Major histocompatibility complex (MHC) molecules are central to development and regulation of the immune system in all jawed vertebrates. MHC class III cytokine genes from the tumor necrosis factor core family, including tumor necrosis factor (TNF) and lymphotoxin alpha and beta (LTA, LTB), are well studied in human and mouse. Orthologues have been identified in several other eutherian species and the cDNA sequences have been reported for a model marsupial, the tammar wallaby. Comparative genomics can help to determine gene function, to understand the evolution of a gene or gene family, and to identify potential regulatory regions. We therefore cloned the genomic region containing the tammar LTB, TNF, and LTA orthologues by "genome walking", using primers designed from known tammar sequences and regions conserved in other species. We isolated two tammar BAC clones containing all three genes. These tammar genes show similar intergenic distances and the same transcriptional orientation as in human and mouse. Gene structures and sequences are also very conserved. By comparing the tammar, human and mouse genomic sequences we were able to identify candidate regulatory regions for these genes in mammals. Full length sequencing of BACs containing the three genes has been partially completed, and reveals the presence of a number of other tammar MHC III orthologues in this region.
authors.affiliation: Comparative Genomics Unit, ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, Australian National University, Canberra, Australia. cross@rsbs.anu.edu.au
authors.forename: J G R
authors.initials: JG
authors.lastname: Cross
authors.forename: G A
authors.initials: GA
authors.lastname: Harrison
authors.forename: P
authors.initials: P
authors.lastname: Coggill
authors.forename: S
authors.initials: S
authors.lastname: Sims
authors.forename: S
authors.initials: S
authors.lastname: Beck
authors.forename: J E
authors.initials: JE
authors.lastname: Deakin
authors.forename: J A Marshall
authors.initials: JA
authors.lastname: Graves
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D033481:Chromosomes, Mammalian; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D016678:Genome; D006801:Humans; D007614:Macropodidae / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha