GENOMIC SCREEN FOR ADULT ONSET GLAUCOMA SUSCEPTIBILITY GENES:  FINE MAPPING
OF CANDIDATE REGIONS

J.L. Wiggs1, 2R.R Allingham, 3L.R Bailey, 2J. August, 2E.A Del Bono, 2B. Broomer, 2K. LaRocque, F. Lennon-Grahm, M. Pericak-Vance,

M. Hauser and 3J.L Haines

1New England Medical Center, Boston, Massachusetts,  USA

2Duke University, USA and 3Vanderbilt University, USA

Previous studies have suggested that multiple genetic defects and possibly environmental factors may influence adult onset glaucoma susceptibility.  To identify the chromosomal locations of adult glaucoma susceptibility genes, we have completed an initial genome screen using two independent pedigree sets (182 total affected sibpairs).  Our initial studies identified 16 chromosomal regions that demonstrated interesting results (lod score >1.0 and/or a p-value <0.05).  Further studies including the second pedigree set identified regions on chromosomes 2, 4, 9, 11, 14, 17 and 19 that continued to produce model-dependent lod scores and/or an MLS > 1.0, while five regions (2, 14, 17p, 17q and 19) produced an MLS > 2.0 (Wiggs et al., Hum Mol Genet  9:  1109-1117).  The purpose of the current study is to further refine these chromosomal regions with a third set of affected sibling pairs and additional markers spanning each chromosomal region at 2-5 cM intervals.  Linkage analysis was performed using multiple methods.  Analysis of the data indicates that markers located in the candidate region on chromosomes 14 and 19 continue to show positive results.  The addition of new sibpairs also identified a new region on chromosome 15.  Further analysis of candidate genes located in these regions is currently underway.