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R.W. Yee; Fine–Mapping and Candidate Gene Analysis of Chromosome 10–Linked Thiel–Behnke Corneal Dystrophy (CDB2) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4932.
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Purpose: We previously mapped Thiel–Behnke corneal dystrophy to chromosome 10q23–q24 (Yee et al. 1997, Genomics 46:152–154). This disease is also referred to as corneal dystrophy Bowman’s type II (CDB2). We previously reported a reduction of the CDB2 locus from 12 cM to 4 cM. We further hypothesized that additional recombination events might have occurred in the pedigree that would allow us to further reduce the locus. We reasoned that all affected patients in the family should share a common haplotype, which is different from another haplotype of the same affected patient as well as different from haplotypes of all unaffected patients. If recombination occurred within this 4 cM or 4.3 Mb DNA, the shared and disease–specific haplotype would be smaller than the whole region. We proposed that it was possible for us to identify this disease–specific haplotype. An additional purpose of this study was to identify disease–specific mutations by candidate gene analysis. Methods: Additional family members that we have not studied before may play crucial role in reduction of the CDB2 locus by linkage and haplotype analysis. We revisited our family and collected blood samples from 6 new members. We also redrew blood samples from 8 members that were included in our previous analysis. DNA was prepared from these 14 individuals and used for candidate gene mutation screening, linkage and haplotype analysis. Results: We analyzed 70% of 18 candidate genes and excluded a total of 5 genes as candidates so far. Most importantly, we reduced the CDB2 locus more than half from 4.3 Mb to 2 Mb, and subsequently reduced the number of candidate genes from 105 to 26, 3 of them were excluded by mutation analysis. Conclusions: The reduction of the CDB2 locus greatly increases the likelihood of cloning this disease gene.
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