A Novel Locus for Keratoconus on 5q14.3–q21.1

Abstract

Abstract: : Purpose: : Previously we presented data suggesting a gene locus for keratoconus on chromosome 21 in a family with an autosomal dominant trait . In that study we performed linkage analysis only with markers on chromsome 21. In this study we expanded our linkage studies in the same family to include markers on all the 22 autosomal chromosomes Methods: : A two–stage genome–wide scan was performed in 27 family members. First linkage analysis was performed with 343 microsatellite markers along the 22 autosomal chromosomes at ∼10 cM density. This was followed by fine mapping at ∼2 cM density, in regions suggestive of linkage. Multipoint linkage analysis was performed using GeneHunter2. Results: Evidence of suggestive linkage from the initial scan was observed at the 82–112 cM region of chromosome 5q14.1–q21.3 with a maximum lod score (LOD) of 3.48. Fine mapping by testing an additional 8 microsatellite markers at 2–3 cM intervals revealed a narrower and higher peak (98–112 cM) with LOD 3.53. By analysis of the recombination of haplotypes, the putative locus of keratoconus was narrowed to a 6 cM region between markers D5S2499 and D5S495. No linkage was detected in this family with any of the other previously reported gene loci for keratoconus. Conclusions: These results indicate a promising new locus which might provide new insights into the pathogenesis of keratoconus.

Keywords: linkage analysis • genetics • keratoconus