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Title: Linkage analysis in highly myopic families
Author: Creer, Rosalind
ISNI:       0000 0004 2751 0529
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2007
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The Family Study of Myopia is a research project aiming to discover genetic loci causing susceptibility to high myopia. As part of this investigation, the heritability of refractive error and other ocular components was estimated for a large Irish-Welsh multi-generational pedigree using variance components analysis software, SOLAR. Heritabilities of 0.39 (p=6.92 x 10"5, S.E.=0.14), 1.00 (p=1.84 x 10"4, S.E.=0.22) and 0.30 (p=0.13, S.E.=0.33) were found for refractive error, mean corneal curvature and axial length, respectively. Heritability of refractive error was also calculated using within-family regression and a Markov Chain Monte Carlo method producing estimates of between 0.12 and 0.73. This high heritability of ocular refraction suggests the potential for finding susceptibility loci for the control and development of refractive error. To pinpoint these loci, areas of chromosomes which have previously been suggested to harbour genes controlling refractive error were investigated to determine whether linkage was present within this family. DNA was extracted from mouthwashes and linkage analysis was performed. SOLAR revealed no significant linkage to the loci tested, reinforcing the theory that myopia is a highly heterogenous disease. The maximum twopoint LOD score was within the MYP6 locus at marker D22S1176 (LOD=1.19). Multipoint analysis showed the maximum LOD score at the MYP3 locus, between markers D12S1605 and D12S354 (LOD =1.37). In a separate study of 96 families containing a highly myopic child and the two parents, the involvement of a candidate gene encoding the protein myocilin (MYOC) was examined using an association analysis. There was weak evidence of over- transmission of allele 3 of MYOC 1, a marker in the 5' untranslated region of the gene, and under-transmission of allele 4 of that same marker (both p<0.05). This suggests MYOC may play a small role in the causation of high myopia development but a larger sample is needed to establish this conclusively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available