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M Voorendt, JJ M Assink, LA Sandkuijl, JB ten Brink, S van Soest, A Reis, PT V M de Jong, AA B Bergen; Genome-Wide Screen for Age-Related Maculopathy in an Isolated Population . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2829.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The aim of this study is to identify genetic factors for age-related maculopathy (ARM) in an isolated community. Methods: Patients with ARM from a genetically isolated population in the Netherlands were ascertained through the registers of ophthalmologists. From all individuals fundus photographs were taken and graded according to the ARM International Classification System. Spouses of the patients and age-matched subjects were included as controls. DNA was isolated from peripheral blood lymphocytes. From all patients and 80 controls genealogical data up to 12 generations has been obtained. A genome-wide screen with 400 polymorphic markers, equally spaced with an interval of 10 cM, was performed in this pedigree. Haplotypes in all patients and controls were constructed, using the alleles from spouses and children if available. Alleles of 400 markers were counted among the patient and control group. A chi-square test was performed to see if some alleles are more abundant in ARM patients compared to controls. If this test was significant an odds ratio was calculated. The genotype data were also analysed with a likelihood ratio statistic to test for linkage disequillibrium. Extensive haplotype analysis was carried out for the locus on 1q25-q31 and the candidate genes ABCA4 and TIMP3. Results: A pedigree with 22 affected ARM individuals was identified. From those 22 patients, 13 were diagnosed to have the endstage of the disease. The age at examination ranged from 66 to 91 years. No obvious haplotype sharing regions in any of the published candidate regions could be found. The chi-square test also showed no significant abundancy of marker alleles in those regions. The genomic screen revealed five new regions of interest (p < 0.05). In these regions additional markers have been tested, and data analysis of those markers is still in progress. Currently we are also including the genealogical data from the patients and 80 controls in the statistical analysis. A clinical follow-up of all patients is ongoing to exclude potential phenocopies. Conclusions: The genes and loci described in the literature as candidates involved in causing ARM were excluded in this isolated population. In the pedigree five new chromosomal regions were found that could be involved in the pathogenesis of ARM.
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