title: Genomic organization and expression of the doublesex-related gene cluster in vertebrates and detection of putative regulatory regions for DMRT1.
abstract: Genes related to the Drosophila melanogaster doublesex and Caenorhabditis elegans mab-3 genes are conserved in human. They are identified by a DNA-binding homology motif, the DM domain, and constitute a gene family (DMRTs). Unlike the invertebrate genes, whose role in the sex-determination process is essentially understood, the function of the different vertebrate DMRT genes is not as clear. Evidence has accumulated for the involvement of DMRT1 in male sex determination and differentiation. DMRT2 (known as terra in zebrafish) seems to be a critical factor for somitogenesis. To contribute to a better understanding of the function of this important gene family, we have analyzed DMRT1, DMRT2, and DMRT3 from the genome model organism Fugu rubripes and the medakafish, a complementary model organism for genetics and functional studies. We found conservation of synteny of human chromosome 9 in F. rubripes and an identical gene cluster organization of the DMRTs in both fish. Although expression analysis and gene linkage mapping in medaka exclude a function for any of the three genes in the primary step of male sex determination, comparison of F. rubripes and human sequences uncovered three putative regulatory regions that might have a role in more downstream events of sex determination and human XY sex reversal.
authors.affiliation: Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Brunner
authors.forename: U
authors.initials: U
authors.lastname: Hornung
authors.forename: Z
authors.initials: Z
authors.lastname: Shan
authors.forename: I
authors.initials: I
authors.lastname: Nanda
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: E
authors.initials: E
authors.lastname: Zend-Ajusch
authors.forename: T
authors.initials: T
authors.lastname: Haaf
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: A
authors.initials: A
authors.lastname: Shima
authors.forename: M
authors.initials: M
authors.lastname: Schmid
authors.forename: V M
authors.initials: VM
authors.lastname: Kalscheuer
authors.forename: M
authors.initials: M
authors.lastname: Schartl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D005091:Exons; D005260:Female; D005399:Fishes / Q000196:embryology / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009990:Oryzias / Q000196:embryology / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D029961:Zebrafish Proteins
chemical_list: C110547:DMRT1 protein; C119852:DMRT2 protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D029961:Zebrafish Proteins; C486539:dmrt2a protein, zebrafish; D012313:RNA; D004247:DNA