Population Isolates and Ophthalmic Diseases.

This article is discussing the relevance between genetic isolates and ophthalmic diseases. It will mainly focus on population isolates and the role they play in searching for the underlying genes responsible for monogenic and complex heterogeneous eye diseases. For some background information, population isolates are a group of individuals who are known to have descended from the founder of a population. Because of this, they have been able to maintain a relative degree of genetic homogeneity due to geographical and cultural isolation. There have been many gains in better understanding the genetic etiology (the genes responsible for casing disease) of age-related macular degeneration and eye diseases that are similar. However, the etiology of the heritable blinding diseases (e.g. primary open-angle glaucoma and myopia) are still issues at hand that are working with the population isolated theory, to hopefully gain a better understanding. Population isolates are found in both recessive traits and complex traits

Population isolates are effective ways to further investigate recessive traits. A high frequency rate of new mutations occurring within humans makes it conceivable that there is a high prevalence of recessive diseases in some isolated populations. This happens because of random chance; also known as genetic drift. This also explains why some alleles are able to be more common or rare over consecutive generations. An increased risk of recessive diseases is also associated with consanguineous relationships meaning blood relatives (incest). Consanguinity is lower than it was in isolated populations and this has been shown in a Finnish isolate study. In the study there were thirty monogenic (meaning only one gene) recessive disorders that are more frequent there than anywhere else. One account for this may be linked to non-random migration of families clustering in small geographical areas.

Retinoschisis is an X-linked retinal disease related to population isolates. This is described as the worsening visual cavity, radial and peripheral superficial retinal detachment. Cases with highest prevalence were reported in Finland based upon age and sex (88 males) from 31 families. This particular ophthalmic disease is located on the short arm of the X-chromosome leaving insight into three other founder mutations with high prevalence disease in Finland families. Some other noted examples of retinal diseases within consanguineous relationships is complex strabismus and nanophthalmos. Complex strabismus is a misalignment of the eye and varies with gaze direction. Several Saudi Arabian families were studied and reported to have a basis for autosomal recessive complex strabismus. Nanophthalmos is very rare and is described by small axial lengths with high-hypermetropia on three separate loci of the eleventh chromosome. There are two forms of this that exist, autosomal dominant and recessive, and there is evidence of a founder effect in the Faroe Islands.

Population isolates are also effective means for studying complex traits in ophthalmic diseases. Age Related Macular Degeneration (AMD) is one example of many complex traits. AMD is characterized by two forms, wet and dry. Dry makes up on average 80% of AMD with being described as serous detachment of the retinal pigment epithelium (RPE). AMD varies considerably between ethnic groups. There was a link reported between the US and Japanese populations in correlation with the complement factor H gene contributing to nearly half of all cases of AMD.

Another example of complex traits is primary open angle glaucoma which is asymptomatic with gradual progressive loss of peripheral vision. This is also accompanied by having a cupped head of the optic nerve. This particular complex trait is reportedly found in the French-Canadian populations of Quebec. Four families were studied and later concluded to have been carrying four MYOC mutations that were believed to have been derived from the original Quebec settlers. Also, 14 additional families with glaucoma carried eight of the MYOC mutation from these original settlers.

In conclusion, it has been both successful and helpful in using population isolates. We now have a better knowledge of recessive traits as well as complex traits and the role they play in ophthalmic disease. Isolated populations may only allow for the identification for a few major diseases; however these genes are identified more efficiently than those from non isolated populations. Being able to identify founder effects helps simplify the analysis of genetic diseases as well as helps the screening service in any populations.

Marcee Amos