Genetic Isolates in Ophthalmic Diseases

Abstract

In recent years, noteworthy gains have been made in unravelling the genetic contribution to some complex ocular diseases, principally age-related macular degeneration. Yet, a relatively poor understanding of the genetic aetiology for many other heritable blinding diseases, such as glaucoma, keratoconus and myopia, remains. Genetic isolates, populations with varying degrees of geographical or cultural seclusion, provide an effective means for investigating the molecular mechanisms involved in human diseases. This is particularly true for rare diseases in which founded alleles can be rapidly driven to a high frequency due to restriction of gene flow in the population. Recent success in complex gene mapping has resulted from the widened linkage disequilibrium (LD) in the genome of genetically isolated populations. An improved understanding of the predisposing genetic risk factors allows for enhanced screening modalities and paves the foundations for the translation of genomic technology into the clinic. This review focuses on the role population isolates have had in the investigation of genes underlying complex eye diseases and discusses their likely usefulness given the expansion of large-scale case-control association studies.

Keywords:

• Founder effect
• complex disease
• glaucoma
• macular degeneration
• refractive error