Mapping the juvenile glaucoma gene

K. Petrukhin, S. G. Fischer, J. M. Liebman, E. Cayanis, S. Kalachikov, H. T. Zhang, R. Ritch, T. C. Gilliam

Research output: Contribution to journalArticlepeer-review


Purpose. Previous linkage studies and recombination mapping have shown that the minimum genetic region (MGR) for JOAG locus includes the interval flanked by D1S210/D1S452 and D1S218/D1S242. This interval contains genetic markers demonstrating the tightest linkage to the disease locus. The purpose of this study is (1) to establish YAC and PAC contigs across the region; (2) to isolate new generic markers from the region and type them in a three-generation JOAG family (3) to isolate candidate genes from the region and analyze them in affected individuals. Methods. Inter-Alu PCR product from YAC clones positive for flanking markers was used to screen a total genomic PAC library. New genetic markers and STS's were developed from PAC ends as well as from random and CA-positive subclones derived from PAC DNA. Exon trapping technique was used fo identify new genes in the MGR. Results. Using previously reported and newly characterized CA-repeats and STS's we establish YAC and partial PAC contigs between D1S210 and D1S218. Assuming no duplications in the region, the order of the previously reported markers is: D1S452/ AFM350yh1 - D1S210 - AFM278ye5 - AFM154xc9 - D1S242 - D1S218; the estimated distance between D1S210 and D1S218 is 1-1.5 Mb. Typing of newly identified genetic markers in a three-generation JOAG family did not reveal informative recombinations which could further delimit the MGR. Up to the moment, we isolated from PAC clones 15 exons utilizing an exon-trapping approach. One of the trapped exons exhibits 100% homology with the previously reported protease inhibitor gene; three other sequences display a weak but significant homology to δ-subunit of H-ATPase, titin (giant protein in charge of muscle elasticity), and proline-rich polypeptides. 11 exons are not homologous to any GenBank entry. Conclusions. Physical mapping and exon trapping allowed the identification of candidate genes for JOAG. Additional family studies and mutation analysis are designed to identify the gene(s) responsible for this condition.

Original languageEnglish
Pages (from-to)S33
JournalInvestigative Ophthalmology and Visual Science
Issue number3
StatePublished - 15 Feb 1996
Externally publishedYes


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