Purchase this article with an account.
R.W. Yee, W. Dai, X. Zhao; Candidate Gene Analysis of Chromosome 10–linked Thiel–Behnke Corneal Dystrophy (CDB2) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5557.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We previously mapped Thiel–Behnke corneal dystrophy, also referred to as corneal dystrophy Bowman’s type II (CDB2), to chromosome 10q23–q24. We further reduced the CDB2 locus to a 2 Mb region by haplotype and linkage analysis. This study is to clone the disease gene by candidate gene mutation screening approaches.
PCR primers were designed for all exons within the coding region of each candidate gene and used for DNA amplification from one unaffected and three affected patients. DNA sequencing was performed directly on the amplified DNA. Polymorphisms in DNA sequence were analyzed. Twenty–five candidate genes within the CDB2 region were screened. This mutation analysis was also performed on alternative splicing variants of these candidate genes. To identify new candidate genes, University of Cailifornia Santa Cruz (UCSC) genome browser was used for retrieving UniGene clusters and localizing them to the CDB2 locus by using the programs developed in our laboratory.
We analyzed 95% of the 25 candidate genes and identified a total of 65 single nucleotide polymorphisms (SNPs). Twenty–eight of them (43%, 28/65) were new SNPs. We also screened for mutation in alternative splicing variants of these candidate genes and found additional 12 SNPs. Bioinformatics and database analysis identified 36 additional candidates for the CDB2 disease gene.
The new SNPs identified in this study are very useful for annotation of the human genome. Mutation screening excludes majority of the 25 genes as candidates. Additional genes and UniGenes identified through bioinformatics and genomic database analysis are promising candidates for the CDB2 disease gene.
This PDF is available to Subscribers Only