Inherited retinal diseases in dogs: advances in gene/mutation discovery

Abstract

1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed.

Mechanistic insight into the progressive retinal atrophy disease in dogs via pathway-based genome-wide association analysis

“…The majority of hereditary PRA diseases in dog are autosomal recessive, while some are X-linked forms or autosomal dominant [1,5,7]. So far, researchers have identified as many as 31 mutations in 24 genes, as underlying cause for canine retinal disease [8]. The methods to identify susceptible genetic variants and genes discovery in canine have seen considerable improvement over the past 20 years [8,9].…”

Autosomal Dominant Retinitis Pigmentosa Due to Class B Rhodopsin Mutations: An Objective Outcome for Future Treatment Trials

“…Major advances in understanding RP disease mechanisms have also resulted from studies of animals with inherited retinal degeneration [9,10]. From a limited number of “animal models” of RP with unknown genetic causes, there was subsequent identification of the molecular basis of many of these retinal degenerations.…”

A novel mutation in PDE6B in Spanish Water Dogs with early‐onset progressive retinal atrophy

“…Mutations in over 20 genes have been identified as causal for PRA in dogs. 2,3 Progressive retinal atrophy occurs in the Spanish Water Dog (SWD) breed. They are one of the many breeds with PRA due to a mutation in the progressive rod-cone degeneration gene (PRCD).…”