Chromosome 10q26 locus and age-related macular degeneration: a progress update

Abstract

Age-related macular degeneration (AMD) is the leading cause of late-onset central vision loss in developed countries. Both genetic and environmental factors contribute to the onset of AMD. Variation at a locus on chromosome 10q26 has been consistently associated with this disease and represents one of the two strongest genetic effects being identified in AMD. At least three genes are located within the bounds of the locus: pleckstrin homology domain containing family A member 1 (PLEKHA1), age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement A serine peptidase 1 (HTRA1), all of which are associated with AMD. Due to the strong linkage disequilibrium (LD) across this region, statistical genetic analysis alone is incapable of distinguishing the effect of an individual gene in the locus. Uncertainty remains, however, in regards to which gene is responsible for the linkage and association of the locus with AMD. Investigating functional consequences of the associated variants and related genes tends to be essential to identifying the biologically responsible gene(s) underlying AMD. This review examines the recent progress and current uncertainty on the genetic and functional analyses of the 10q26 locus in AMD with a focus on ARMS2 and HTRA1. A discussion, which entails the possible multi-faceted approaches for pinpointing the gene(s) in the locus underlying the pathogenesis of AMD, is also included.

Keywords: ARMS2; HTRA1; PLEKHA1; age-related macular degeneration; gene annotation; indel; promoter; single nucleotide polymorphism; transcript splice variants.