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S. Monemi, A. Child, O. Lehmann, G. Spaeth, R. Crick, M. Sarfarazi; Genome Scan of Two Large Families with Adult-Onset Primary Open Angle Glaucoma (POAG) Suggests a Probable Locus on 5q33-q35 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1128.
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Purpose: To identify new chromosomal locations in two large families with adult-onset POAG. Methods: The first POAG family has a total of 99 members in five generations and 40 of them sampled already (13 affected, 4 OH and 23 unaffected). The second family has 108 members in four generations and 53 of them sampled previously (7 affected, 5 glaucoma suspect and 41 unaffected). Genome scan was carried out with ABI and CHLC florescent linkage mapping sets. Saturation mapping were carried out and altogether, the first family genotyped for 900 and the second for 300 polymorphic DNA markers. All genotypic data entered into a database management system (DMS) and subsequently pedigrees were exported to Cyrillic program. The most likely inherited haplotypes were constructed manually for each chromosome and for each of the two pedigrees. Results: Initial data analysis excluded linkage to previously reported POAG loci of GLC1B to GLC1F but identified potential regions on chromosomes 1, 3, 5, 6, 7, 8, 10, 15 and 16. However, additional saturation mapping and haplotype analysis ruled out linkage to chromosomes 1, 3, 6, 7, 8, 10, 15 and 16. Interestingly, all 7 affected individuals from one family consistently shared an affected haplotype for 30 consecutive DNA markers from D5S2497 to D5S498, a region of approximately 36 cM. The other family also shared a smaller portion of the same region. We are currently in the process of developing additional polymorphic markers from BAC clones covering smaller areas of this region showing linkage gaps of >3-5 cM. Saturation mapping with our newly developed DNA markers and linkage study of additional POAG families to this region will provide a more detailed account of this initial observation and potentially narrows down this region further. Conclusions: A new locus for adult-onset POAG may potentially be linked to the 5q33-5q35 region. Supported by EY-09947 and M01RR-06192.
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