For linkage region on chromosome 5, further fine mapping was performed on a total of three pedigrees. Linkage analysis revealed a maximum two point LOD score of 4.81 at marker D5S2505. Haplotype analysis narrowed the linkage region to 5p15.33-p15.2. Resequencing of five candidate genes, IRX2, IRX1, POLS, CCT5 and CTNND2 within the linkage region did not reveal any myopia mutation. They were therefore excluded as the myopia causative gene. Genotyping of 41 SNPs within this region in a Chinese cohort of 94 high myopia cases and 94 control subjects showed that the allele and genotypes distributions of rs370010 was significantly different between cases and controls (genotype P= 0.01176, allele P=0.00271 and trend P=0.00375). This SNP is located within a hypothetical gene LOC442129. After multiple testing corrections, none of the SNP remained significantly associated with high myopia. This is a novel myopia locus. Further work to identify the myopia gene in this region would involve candidate gene resequencing, family linkage analysis and gene-based SNPs association analysis. / High myopia is defined as refractive error below or equal to -6 dioptres (D). The prevalence of high myopia varies among different populations. The most common pathological structural abnormality in high myopia is the excessive lengthening of the posterior segment of the ocular globe. Apart from causing impaired vision, it may lead to severe ocular complications. The precise mechanistic role of genes and environmental factors in the development of high myopia is still uncertain. Studies of twins and families suggested that heredity is a major contributing factor. While no myopia gene has yet to be identified, 14 putative loci have been found on many chromosomes. In this study, we have utilized different approaches to map the myopia locus in the Chinese population. / In our family-based genome-wide scan program, the whole genome of Chinese high myopia pedigrees was screened by using microsatellite markers. Two point LOD scores > 1 were observed on chromosomes 12 and 5. Regions were further analyzed by fine mapping. For linkage region on chromosome 12, a maximum two point LOD score of 2.71 was obtained at marker D12S88 and suggested linkage region was narrowed at 12q21.31-q22 by haplotype analysis. Lumican located in this region was screened and no segregation of polymorphism was observed within the pedigree. The suggested locus in this study overlapped with the MYP3 but with a smaller interval than the one reported. Lumican was excluded to be the myopia gene in this locus. / In the candidate-gene program, the paired box gene 6 (PAX6) on 11p13, was first studied. Two dinucleotide repeats (AC)m and (AG)n in the promoter region were found to be highly polymorphic. Association was observed between these two repeats with high myopia in which patients had high repeat number in both (AC) m and (AG)n (p-value=0.0001317 and p-value=0.001). Our results indicated that the Chinese population does not show association between high myopia and polymorphisms in PAX6 coding region but the AC and AG dinucleotide repeats in the promoter region was significantly associated with high myopia. / Lam, Ching Yan. / "August 2007." / Source: Dissertation Abstracts International, Volume: 69-07, Section: B, page: 4103. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344085 |
| Date | January 2007 |
| Contributors | Lam, Ching Yan., Chinese University of Hong Kong Graduate School. Division of Ophthalmology and Visual Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (1 v. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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