Sorsby's fundus dystrophy in the British Isles: demonstration of a striking founder effect by microsatellite-generated haplotypes.

• DOI: 10.1101/gr.6.2.92
• Publication Date: 2007-06-05T21:18:07Z
• Authors: S D Wijesuriya; K Evans; M R Jay; C Davison; B H Weber; A C Bird; S S Bhattacharya; C Y Gregory
• Keywords: Founder effect

Sorsby's fundus dystrophy (SFD) has been mapped to a genetic interval of 8 cM between loci D22S275 and D22S278. A total 15 families, unrelated on the basis genealogy expressing SFD phenotype were identified from large data base eye disease families originating diverse parts British Isles. The identification same Ser181Cys mutation cosegregating with in each family led us consider hypothesis founder effect being present. In all studied, relatively infrequent allele (occurring just 11% control group) was associated at marker locus D22S280. highly significant disease-associated haplotype, spanning across 3 locus, conserved 11 (68% affected chromosomes); further extended haplotype up 7 cM, 5 (27% SFD-associated chromosomes) possibly represents ancestral haplotype. This analysis refined TIMP3 gene localization 1- 3-cM D22S273 D22S281 provides strong evidence for single mutational event responsible majority