Genetic modifiers as relevant biological variables of eye disorders

Abstract

From early in the study of mammalian genetics, it was clear that modifiers can have a striking influence on phenotypes. Today, several modifiers have now been studied in enough detail to allow a glimpse of how they function and influence our perspective of disease. With respect to diseases of the eye, some modifiers are an important source of phenotypic variation that can elucidate how genes function in networks to collectively shape ocular anatomy and physiology, thus influencing our understanding of basic biology. Other modifiers represent an opportunity for new therapeutic targets, whose manipulation could be used to mitigate ophthalmic disease. Here, we review progress in the study of genetic modifiers of eye disorders, with examples from mice and humans that together illustrate the ubiquitous nature of genetic modifiers and why they are relevant biological variables in experimental design. Special emphasis is given to ophthalmic modifiers in mice, especially those relevant to selection of genetic background and those that might inadvertently be a source of experimental variability. These modifiers are capable of influencing interpretations of many experiments using targeted genome manipulations such as knockouts or transgenics. Whereas there are fewer examples of modifiers of eye disorders in humans with a molecular identification, there is ample evidence that they exist and should be considered as a relevant biological variable in human genetic studies as well.