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L.A. Welsh, A. Child, R.P. Crick, E. Heon, M. Sarfarazi; Genome Wide Scan of 5 Families with Adult Onset Primary Open Angle Glaucoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1121.
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Purpose: To perform a random genome screening and to identify chromosomal locations of genes in 5 large families with Adult-Onset Primary Open Angle Glaucoma. Methods: Four British and one Canadian family with 25 and 14 affected individuals respectively were included in this study. The phenotype of affected subjects included high to moderate intraocular pressure, onset after 40 years of age and glaucomatous visual field loss. Collectively, 98 individuals were sampled of whom 32 affected, 1 glaucoma suspect and 2 unaffected subjects were selected for a random genome screening. Our strategy was to first screen the genome with 169 markers at 20 cM intervals, and follow that up by another 217 intervening markers for a final resolution of 5-10 cM. Prospective regions were investigated by genotyping 14 additional members of these families and by using closely linked flanking markers. All genotypic data were entered into a database management system and subsequently pedigrees were exported to Cyrillic program for construction and inspection of inherited haplotypes. Results: Over 500 and 300 DNA markers respectively were genotyped in one Canadian and four British families. The most likely affected haplotypes were constructed manually for each chromosome and for a total of 49 affected and normal individuals. Analysis of these haplotypes and observation of positive LOD scores initially revealed potential hint of linkage for regions on chromosomes 1, 2, 3, 4, 5, 10, 12, 13, 16, 20, 21 and 22. However, further saturation mapping could not establish firm linkage for most of these regions. Locations that are still consistent with linkage include regions on chromosomes 4q, 10q and 12q. Confirmation of this initial observation and saturating mapping of these 3 regions with additional members of these families are currently in progress. Conclusions: We have performed a genome scan in 5 POAG families and tentatively mapped their genetic loci on chromosomes 4, 10 and 12. Supported by EY-09947 and M01RR-06192
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