Candidate gene screening
The process of candidate gene screening involves screening for mutations of genes that are abundantly expressed within a tissue and are either important for function or specifically expressed only in that tissue. Sometimes, the candidate gene is one that recapitulates the human disease in transgenic animals. Examples of candidate gene screening discoveries include the findings of mutations of peripherin/RDS in autosomal dominant RP and macular dystrophies and the finding of mutations of the rod cyclic guanosine monophosphate (cGMP) β-subunit of rod phosphodiesterase and the cGMP–gated cation channel in autosomal recessive RP.
Positional candidate gene screening
Whenever linkage studies localize a gene to a given chromosomal region, genes already known to reside in the same region become candidate genes for that disease. Following are some examples of disease localization that resulted from linkage to a given region, which in turn led to finding the disease-causing gene by screening for mutations of genes in the region: autosomal dominant RP from rhodopsin mutations (3q); Sorsby fundus dystrophy from TIMP3 mutations (22q); and Oguchi disease from point deletions within the arrestin gene (2q).
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.