Investigation of founder effects for the Thr377Met Myocilinmutation in glaucoma families from differing ethnic backgrounds

[摘要] Purpose: The aim of this study was to determine if there is a commonfounder for the Thr377Met myocilin mutation in primary open angleglaucoma (POAG) families with various ethnic backgrounds.Methods: Genomic DNA of 24 POAG-affected individuals from ninepedigrees with the Thr377Met mutation and 104 unaffected family memberswas genotyped with six microsatellite markers and four single nucleotidepolymorphisms. The families were from Greece, India, Finland, the USA,and Australia. To assess the degree of linkage disequilibrium acrossMYOC in the general population we also investigated data generatedfrom the HapMap consortium.Results: Three distinct haplotypes associated with the Thr377Metmyocilin mutation were identified. The families from the USA andGreece, as well as the three Australian families originating from Greeceand the former Yugoslavian Republic of Macedonia had one commonhaplotype. Interestingly, however, HapMap data suggest that linkagedisequilibrium across MYOC was not strong.Conclusions: The Thr377Met myocilin mutation has arisen at leastthree separate times. Evidence for genetic founder effects in thisprevalent age-related, yet heterogeneous, disease has importantimplications for future gene identification strategies.

[学科分类] 生物化学/生物物理