RECOMBINATIONAL AND PHYSICAL MAPPING OF THE LOCUS FOR PRIMARY OPEN-ANGLE GLAUCOMA (GLC1A) ON CHROMOSOME 1Q23-Q25

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG , GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombin ant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2. 8 Mb apart on a 4.7-Mb contig that we have completed between the D1S28 51 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The ne w GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 res triction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compati ble with its predominant cytogenetic location on the 1q24 G-band. Fina lly, we have excluded important candidate genes, including genes codin g for three ATPases (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our resul ts provide a basis to identify the GLC1A gene. (C) 1997 Academic Press .