title: Organization and annotation of the Xcat critical region: elimination of seven positional candidate genes.
abstract: Xcat mice display X-linked congenital cataracts and are a mouse model for the human X-linked cataract disease Nance Horan syndrome (NHS). The genetic defect in Xcat mice and NHS patients is not known. We isolated and sequenced a BAC contig representing a portion of the Xcat critical region. We combined our sequencing data with the most recent mouse sequence assemblies from both Celera and public databases. The sequence of the 2.2-Mb Xcat critical region was then analyzed for potential Xcat candidate genes. The coding regions of the seven known genes within this area (Rai2, Rbbp7, Ctps2, Calb3, Grpr, Reps2, and Syap1) were sequenced in Xcat mice and no mutations were detected. The expression of Rai2 was quantitatively identical in wild-type and Xcat mutant eyes. These results indicate that the Xcat mutation is within a novel, undiscovered gene.
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Huang
authors.forename: Scarlett
authors.initials: S
authors.lastname: Geunes-Boyer
authors.forename: Sufen
authors.initials: S
authors.lastname: Wu
authors.forename: Amalia
authors.initials: A
authors.lastname: Dutra
authors.forename: Jack
authors.initials: J
authors.lastname: Favor
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D020451:Contig Mapping; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014960:X Chromosome / Q000235:genetics*
chemical_list: C078338:CTF4 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; C489722:REPS2 protein, human; D022821:RNA Splice Sites; C492525:Reps2 protein, mouse; D029701:Saccharomyces cerevisiae Proteins