Identification of the gene mutation associated with North Carolina macular dystrophy

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North Carolina macular dystrophy (NCMD) is an autosomal dominant disease of the central retina which was mapped already in 1993 to the long arm of chromosome 6. Subsequently, fine mapping localized the genetic defect to a 1.7 megabase pair region; however, despite major efforts from several research groups, the disease-associated gene has not been found so far. All chromosome 6 associated NCMD patients have an identical haplotype suggesting an ancestral origin of the sought-after disease mutation. It is the goal of the project to use state-of-the-art technology in high-throughput sequencing to determine all sequence variants of the minimal candidate region in a patient and the two parents. Bioinformatics analysis will take advantage of the data from the 1000 genomes project and should allow reducing the number of variants between 5 and a maximum of 20. These variants will then be functionally tested for pathogenicity. In addition, the deep sequencing data are amenable for detection of insertion, deletion and inversion events. Also, we plan to search the minimal candidate region for larger genomic rearrangements by Southern blot analysis. Together, these approaches should result in the identification of the genetic defect associated with NCMD and thus should provide the basis for future studies into the function and dysfunction of the NCMD gene.