Physical and genetic mapping of the macular corneal dystrophy locuson chromosome 16q and exclusion of TAT and LCAT as candidate genes

[摘要] Purpose: Macular corneal dystrophy (MCD) is an inherited autosomalrecessive disorder that has been subdivided into three immunophenotypes,MCD types I, IA and II. We previously mapped the MCD type I gene tochromosome 16q22 and suggested that the MCD type II gene was linked tothe same region. The purpose of this study was to construct a genomiccontig spanning the MCD region and to narrow the MCD critical intervalby haplotype analysis. The TAT and LCAT genes were mapped to determineif they might be the MCD gene.Methods: The MCD contig was constructed by screening YAC, PAC, andBAC libraries with microsatellite, STS and EST markers, employing asystematic "DNA walking" technique. Polymorphic markers mapped andordered on the contig were used to screen the MCD affected individualsand their family members for haplotype analysis.Results: Twenty-two YAC, 30 PAC, and 17 BAC clones were mapped toform the MCD contig. Markers mapped on the contig include 19microsatellite, 14 STS, and 15 EST markers. Moreover, 18 novel STSmarkers were generated. Using the mapped and ordered microsatellitemarkers, haplotype analysis on 21 individuals with MCD type I or type IIand their family members from Iceland narrowed the MCD interval to 3overlapping PAC clones. In addition, the TAT and LCAT genes were mappedoutside the MCD region.Conclusions: We established a genomic contig for the MCD region anddramatically narrowed the MCD critical interval. Mapping data show thatthe TAT and LCAT genes are not the cause of MCD.

[学科分类] 生物化学/生物物理