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.

Leber congenital amaurosis: Clinical correlations with genotypes, gene therapy trials update, and future directions

“…Today LCA is recognized as a genetically heterogeneous recessively inherited group of retinal dystrophies that affects 1 in 81,000 3 to 1 in 30,000 4 live births, although it may be more common in communities that are relatively genetically isolated or in countries with common consanguineous pairings. 5 LCA accounts for over 5% of all inherited retinopathies and 20% of children attending schools for the visually impaired. 2 Patients usually present at birth with profound vision loss and pendular nystagmus.…”

The Association between Time Spent Outdoors and Myopia Using a Novel Biomarker of Outdoor Light Exposure

“…Norfolk Island is an ideal location in which to undertake ophthalmic epidemiological research because of its small population, inherent geographical and genetic isolation, 40 and history of research participation including a study in the early 21st century investigating the genetic determinants of cardiovascular disease. 41 An additional reason to study this island population is because the subtropical climate is relatively constant year round.…”

Distribution of conjunctival ultraviolet autoflourescence in a population-based study: the Norfolk Island Eye Study

“…Such isolated populations have already proved beneficial in increasing our understanding of the genetic determinants of simple and complex disease in ophthalmology. 18 In addition, Norfolk Island is geographically isolated, has a very stable population with restricted migration, and has consistent sun/UV exposure and low levels of pollution.…”