title: DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue.
abstract: The gene DACH is a human homologue of Drosophila melanogaster dachshund (dac), which encodes a nuclear factor essential for determining cell fates in the eye, leg, and nervous system of the fly. To investigate possible connections between DACH and inherited developmental disorders, we have characterized the human DACH genomic structure and investigated the tissue and cellular distribution of the mouse DACH1 protein during development. DACH spans 400 kb and is encoded by 12 exons. The predominant DACH transcript is 5.2 kb and encodes a 706-amino-acid protein with an observed molecular weight of 97 kDa.DACH mRNA was detected in multiple adult human tissues including kidney and heart. The mouse DACH1 protein was immunolocalized to specific cell types within the developing kidneys, eyes, cochleae, and limb buds. Data suggest genetic linkage of the limb bud patterning defect postaxial polydactyly type A (designated PAP-A2, MIM 602085) to a 28-cM interval on chromosome 13 that includes DACH. However, mutation analysis of DACH in this PAP-A2 pedigree revealed no sequence differences in the coding region, splice sites, or proximal promoter region. The data presented will allow for the analysis of DACH as a candidate for other developmental disorders affecting the limbs, kidneys, eyes, ears, and other sites of DACH expression.
authors.affiliation: Craniofacial Development Section, NIAMS, National Institutes of Health, Bethesda, Maryland 20892-2745, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Ayres
authors.forename: L
authors.initials: L
authors.lastname: Shum
authors.forename: A N
authors.initials: AN
authors.lastname: Akarsu
authors.forename: R
authors.initials: R
authors.lastname: Dashner
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Ikura
authors.forename: H C
authors.initials: HC
authors.lastname: Slavkin
authors.forename: G H
authors.initials: GH
authors.lastname: Nuckolls
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D004622:Embryo, Mammalian / Q000378:metabolism; D005091:Exons; D005192:Family Health; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007438:Introns; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D017689:Polydactyly / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C103968:dac protein, Drosophila; D012313:RNA