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Jiaqi Zhou, Heng Xu, Renyuan Chu; Genome-wide Association Study In Pathological Myopia Nuclear Padigrees. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4443.
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To investigate the new candidate genes of pathological myopia in copy number deletion regions by genome-wide scan of nuclear pedigrees.
The study included 31 pathological myopia nuclear pedigrees. Peripheral blood was collected from each member of these pedigrees and genome DNA was extracted. The healthy people in these nuclear pedigrees were used as normal controls. Affymetrix Human SNP Assay 6.0 was used in genome-wide association (GWA) study. De novo copy number varies in genome DNA were analyzed using CNVs as genetic marker and the candidate genes were looked for in the CNVs hot spot. The results were compared with the healthy people in nuclear pedigrees and database. Real-time PCR was used to exclude the false-positive CNVs in the meaningful candidate copy number regions.
Thirty-one nuclear pedigrees (96 members) were included in this study. Kernel Smoothing algorithm, Hidden Markov Model (HMM) algorithm and Segmentation algorithm were used in the analysis process. Two important CNV deletion regions were found using all the three algorithms. In a nuclear pedigree, we found a non-recorded CNV deletion region (≈100kb) at chromosome 4q23 in both the patient and his sick mother. This region was just in the high myopia loci MYP11. Gene Candidate I was in this deletion region. In another nuclear pedigree, we found a non-recorded de novo CNV deletion region (≈350kb) at chromosome 9p24.3. The CNV deletion region was not found in the patient’s normal parent. There is a gene Candidate II in this region. One meaningful CNV deletion region were found using both HMM algorithm and Segmentation algorithm. In a nuclear pedigree, a non-recorded de novo CNV deletion region (≈100kb) was found at chromosome Xq25. The CNV deletion region was not found in the patient’s normal parent. This region was just in the high myopia loci MYP13. There is a candidate gene ACTRT1 in this region. The analysis of the three important CNV deletion regions by Real-time PCR confirmed that the three candidate CNV regions do exist.
Candidate I, Candidate II and ACTRT1 are three promising candidate genes of pathological myopia. It is a pity that there is no overlap of the three CNV deletion regions in all the cases. Further investigations such as verifying the three candidate genes in large sporadic samples and functional researches should be done in order to discover the disease causing genes.
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