title: Characterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant.
abstract: Oral-facial-digital type 1 (OFD1) syndrome is an X-linked dominant condition characterized by malformations of the face, oral cavity, and digits. The responsible gene, OFD1, maps to human Xp22 and has an unknown function. We isolated and characterized the mouse Ofd1 gene and showed that it is subject to X-inactivation, in contrast to the human gene. Furthermore, we excluded a role for Ofd1 in the pathogenesis of the spontaneous mouse mutant Xpl, which had been proposed as a mouse model for this condition. Comparative sequence analysis demonstrated that OFD1 is conserved among vertebrates and absent in invertebrates. This analysis allowed the identification of evolutionarily conserved domains in the protein. Finally, we report the identification of 18 apparently nonfunctional OFD1 copies, organized in repeat units on the human Y chromosome. These degenerate OFD1-Y genes probably derived from the ancestral Y homologue of the X-linked gene. The high level of sequence identity among the different units suggests that duplication events have recently occurred during evolution.
authors.affiliation: Telethon Institute of Genetics and Medicine, 80131 Naples, Italy.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Ferrante
authors.forename: Adriano
authors.initials: A
authors.lastname: Barra
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Truong
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Christine M
authors.initials: CM
authors.lastname: Disteche
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004195:Disease Models, Animal; D004303:Dosage Compensation, Genetic; D040461:Gene Components; D018628:Gene Dosage; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment; D012730:Sex Chromosomes; D014018:Tissue Distribution
chemical_list: D006360:Heat-Shock Proteins; C086058:ODF1 protein, human; C115130:OFD1 protein, human; C490109:Odf1 protein, mouse; D011506:Proteins