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Autosomal dominant Stargardt-like macular dystrophy: founder effect and reassessment of genetic heterogeneity
Journal article   Peer reviewed

Autosomal dominant Stargardt-like macular dystrophy: founder effect and reassessment of genetic heterogeneity

Larry A Donoso, Arcilee T Frost, Edwin M Stone, Richard G Weleber, Ian M MacDonald, Gregory S Hageman, Gerhard W Cibis, Robert Ritter III and Albert O Edwards
Archives of ophthalmology (1960), Vol.119(4), pp.564-570
04/2001
DOI: 10.1001/archopht.119.4.564
PMID: 11296022

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Abstract

To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor. Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed. We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes. Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions. The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited in an autosomal dominant pattern.
Genetic Markers Haplotypes Humans Male Chromosome Mapping Chromosomes, Human, Pair 6 - genetics Genetic Heterogeneity Founder Effect Genes, Dominant Macular Degeneration - genetics DNA - analysis Pedigree Female Genetic Linkage - genetics Genealogy and Heraldry

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