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D. Wang, B.J. Fan, P.O. S. Tam, J. Chua, D.S. C. Lam, C.P. Pang; A Genome–Wide Scan Maps a Novel Juvenile–Onset Primary Open Angle Glaucoma Locus to Chromosome 15q . Invest. Ophthalmol. Vis. Sci. 2006;47(13):186.
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© ARVO (1962-2015); The Authors (2016-present)
To map the disease–associated locus of a family with autosomal dominant juvenile–onset primary open angle glaucoma (JOAG).
Complete ophthalmic examination was conducted and genomic DNA obtained from 21 member of a Chinese family, in which 8 were confirmed JOAG patients. MYOC, OPTN and WDR36 were screened for sequence alterations by PCR and direct sequencing. Genome–wide scanning was carried out using the ABI PRISM Linkage Mapping Set MD–10. Genescan and Genotyper software packages were used to call genotypes. Two–point and multi–point linkage analyses were performed with the MLINK, ILINK and LINKMAP programs. For fine mapping, additional markers flanking the most promising region on chromosome 15q with a resolution of 1.5cM were also analyzed. The significance of LOD scores was tested with simulation analyses using FASTLINK. Haplotypes were constructed using Simwalk2. Three candidate genes (NR2E3, SMAD6, CNL6) located within the critical region were screened for mutations.
MYOC, OPTN and WDR36 mutations were excluded in all family members. A maximum two–point LOD score value of 3.31 at theta = 0.0 was obtained for the marker D15S125. Three adjacent markers, D15S153, D15S1028 and D15S161, gave two–point LOD score values of 3.02, 1.95 and 1.81, at theta = 0.0, respectively. Haplotype analysis and recombination mapping further confined this region to 15q22–q24 within a genetic distance of 17 cM flanked by D15S1036 and D15S1005. Screening of NR2E3, SMAD6, CNL6 revealed no mutations in all coding exons or splicing junctions.
Our results provided the mapping of a novel locus for JOAG at 15q22–q24. Further search for the disease causative gene in this new JOAG locus is in progress.
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