title: Genome-wide scan of granular corneal dystrophy, type II: confirmation of chromosome 5q31 and identification of new co-segregated loci on chromosome 3q26.3.
abstract: Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected novel nine candidate loci for CGD2. In simulation analysis, the only 3q26.3 region including neuroligin 1 gene (NLGN1) was supported by empirical statistic significance. To investigate the effect of genetic heterogeneity in linkage analysis, we classified CGD2 families into two subgroups. Although we could not find a significant evidence for correlation between the 3q26.3 region and CGD2 phenotypes, this first genome-wide analysis with CGD2 families in Korea has a very important value for offering insights in genetics of CGD2. In addition, the co-segregating loci with CGD2 including 3q26.3 would be a good target for further study to understand the pathophysiology of CGD2.
authors.affiliation: Department of Biochemistry School of Medicine Ewha Womans University Seoul, Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Kwang Joong
authors.initials: KJ
authors.lastname: Kim
authors.forename: Han Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Jeong
authors.initials: J
authors.lastname: Bok
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Jung
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyung Lae
authors.initials: HL
authors.lastname: Kim
mesh_terms: D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003198:Computer Simulation; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D053773:Transforming Growth Factor beta1; C093438:neuroligin 1