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M. Sarfarazi, A. DaSilva, L. Welsh, J. Aragon–Martin, L. Wilson, S. Monemi, T. Rezaie, A. Child; Genome Scan Analysis of 139 Families With Adult–Onset Primary Open Angle Glaucoma (POAG) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):47.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To perform a new genome scan and to identify new genetic loci for adult–onset POAG. Methods: DNA samples of 638 subjects from 139 POAG families (400 affected, 26 glaucoma suspect and 212 normal) were genotyped for 410 polymorphic markers from the entire genome. DNA samples from a minimum of 2 (and maximum of 8) affected subjects per kindred were included in the study. Genotypic data transferred into DMS database and, thereafter, exported to CYRILLIC for constructing the most likely inherited haplotypes for each chromosome and in each family. Two–point LOD scores were calculated first for the entire genotypic data and, again for the affected meioses only. Results: Overall, 245,706 genotypes representing 591 potential informative meioses were obtained and included in our data analysis. DNA samples from 1,087 subjects of these 139 families are currently available for further genotyping and saturation mapping. Inspection of inherited haplotypes indicated that a number of these families may be segregating with GLC1B, GLC1C, GLC1D, GLC1G or GLC1H loci. Linkage evaluation to GLC1A, GLC1E, GLC1F and other provisional loci on 2, 10, 14 and 15 are still in progress. Our preliminary data analysis identified 2 different families that produced LOD scores of 2.22 and 2.20 with D11S2363 and D14S592 respectively. Thirty families provided LOD scores between 1.0 and 2.0 with one or more STRP markers. Forty–seven families showed LOD scores between 0.5 and 1.0 with various DNA markers. When genotypic data was analyzed for the "Affected Meioses Only", LOD scores ranging from 2.03 to 2.98 were obtained with 23 STRP markers and scores from 3.13 to 3.52 with 4 DNA markers of D1S1589, D4S1625, GATA104 (on Chr. 7q31) and GATA198B05 (on Chr. 22). A comprehensive saturation mapping, haplotype construction and data analysis for these potentially new POAG regions are currently in progress. Conclusions: As this is the most comprehensive genome scan that includes over 400 affected subjects, we anticipate that new POAG loci will be confirmed by this study. Supported by EY–09947 and M01RR–06192.
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