Linkage Analysis in Keratoconus: Replication of Locus 5q21.2 and Identification of Other Suggestive Loci
| Autor: | Luca Buzzonetti, Costantina Pizzicoli, Antonio Laborante, Patrizia De Bonis, Michele Di Perna, Nicola Delle Noci, Luigi Bisceglia, Leopoldo Zelante, Francesco Giuliani, Lucia Fischetti |
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| Rok vydání: | 2009 |
| Předmět: |
Chromosomes
Human Pair 14 Genetics education.field_of_study Genotype Genetic Linkage Population Chromosome Mapping Family aggregation Locus (genetics) Biology Keratoconus Genetic analysis Pedigree Genetic linkage Chromosomal region Chromosomes Human Pair 5 Humans Microsatellite Genetic Predisposition to Disease Lod Score education Algorithms Microsatellite Repeats |
| Zdroj: | Investigative Opthalmology & Visual Science. 50:1081 |
| ISSN: | 1552-5783 |
| Popis: | Purpose Keratoconus (KC) is the most common indication for corneal transplantation in the Western world, with etiologic mechanisms still poorly understood. The disease prevalence in the general population is approximately 1:2000, and familial aggregation, together with increased familial risk, suggests important genetic influences on its pathogenesis. To date, several loci for familial keratoconus have been described, without the identification of any responsible gene in the respective mapped intervals. The aim of this study was to identify causative/susceptibility genes for keratoconus. Methods A total of 133 individuals (77 affected and 59 unaffected) of 25 families from southern Italy were genotyped using microsatellite markers and included in a genome-wide scan. Nonparametric and parametric analysis using an affected-only strategy were calculated by using genetic algorithm software. Results The chromosomal regions 5q32-q33, 5q21.2, 14q11.2, 15q2.32 exhibited the strongest evidence of linkage by nonparametric analysis (NPL = 3.22, 2.73, 2.62, and 2.32, respectively). The regions 5q32-q33 and 14q11.2 were also supported by multipoint parametric analysis, for which heterogeneity LOD (HLOD) scores of 2.45 (alpha = 0.54) and 2.09 (alpha = 0.46), respectively, were obtained under an affected-only dominant model. Conclusions This study represents the first KC linkage replication study on the chromosomal region 5q21.2 and reports evidence of suggestive linkage in several regions for which suggestive or significant linkage has been previously detected in different populations. |
| Databáze: | OpenAIRE |
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