Linkage analysis for age-related macular degeneration supports agene on chromosome 10q26

[摘要] Purpose: Age-related macular degeneration (AMD) is a retinaldegenerative disease that is the leading cause of blindness worldwide inindividuals over the age of 60. Although the etiology of AMD remainslargely unknown, numerous studies have suggested both genetic andenvironmental influences. A previous study of affected multiplexfamilies identified four chromosomal regions that potentially harbor AMDsusceptibility genes. The purpose of our study was to furtherinvestigate these regions with additional microsatellite marker coveragein our independent data set.Methods: We examined regions on chromosomes 1q, 9p, 10q, and 17q forgenetic linkage in our 70 multiplex families (consisting of 133 affectedsibpairs). Two point heterogeneity LOD score (HLOD) and nonparametricLOD score (MLS) analyses were performed for disease models defined bythe most severe status in either eye. Conditional analyses wereperformed using apolipoprotein E (APOE) alleles as covariates insemiparametric LOD (LOD*) score calculations.Results: Regions on chromosomes 1q, 9p, and 17q did not provideevidence of linkage in our data set. However, markers D10S1230 andD10S1656 on chromosome 10q26 generated maximum HLOD scores of 1.52 and1.13, respectively. Marker D10S1230 also generated an MLS score of 1.56in stage 4 and 5 individuals. Controlling for the potential effect ofthe APOE-ε4 allele did not substantially alter these scores.Conclusions: With the inclusion of this study, at least five AMDdata sets provide support of genetic linkage to 10q26. Such consistencyand confirmation of evidence strongly suggests that this region shouldbe the subject of further detailed genomic efforts for the disease.

[学科分类] 生物化学/生物物理