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The focus in the laboratory is to identify and characterize genes that cause human genetic disease. The diseases studied in the laboratory include the craniofacial disorder, Treacher Collins syndrome, the mental retardation syndrome, Cri du Chat, familial chondrocalcinosis, a form of arthritis and Wolfram Syndrome, a neurodegenerative disorder whose main symptoms include diabetes insipidus, diabetes mellitus, optic atrophy and deafness. These disorders have been localized to human chromosomes 5 and 4q. Projects include positional cloning of familial chondrocalcinosis and a second locus for Wolfram Syndrome. Identification of genes includes the use of linkage analysis, gene mapping, cloning, bioinformatics and mutation detection.
A large focus of the laboratory is the characterization of the Treacher Collins syndrome gene. The protein treacle has homology to a family of nucleolar phosphoproteins but the function of the protein and its role in craniofacial development is not known. The mouse homologue of the protein has also been identified. The developmental expression of the gene has been delineated using whole-mount mouse in-situ hybridization and the gene is expressed in an appropriate temporal and spatial manner. In addition, the protein has been confirmed to be a nucleolar phosphoprotein by localization studies using GFP-fusion constructs and phosphorylation studies. The protein is phosphorylated in a cell-cycle dependent manner. Current studies include the use of yeast-two hybrid screens to identify protein partners for treacle and the construction of a conditional knockout mouse model for Treacher Collins syndrome.