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Moulinath Acharya, Priyanka Pandey; Disease-phenotype deconvolution in genetic eye diseases using Online Mendelian Inheritance in Man (OMIM) database. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1262.
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Despite massive improvements of the genomic technologies during past few years, it is still an uphill task to capture organ-specific disease “phenomes”. This is even more challenging for the eye since it is a unique sensory organ comprising different tissue types derived from all three germinal layers. Here we attempt to deconstruct genetic eye diseases into primary phenotypic features thereby understanding complex relationship between genome and phenome in ocular diseases.
Using information in the OMIM as primary resource, we created a database for genetic eye diseases. We used three separate filters in OMIM to obtain equal number of entries for eye disorders considering primarily two features namely, “phenotype and molecular basis known” and “gene description”. We used custom written Perl and UNIX scripts to analyze genotype and phenotype information for each disease.
Both features mentioned in the methods yielded 527 distinct eye disorders for a single filter in OMIM. These eye disorders were associated with 440 unique protein-coding genes. 520 out of 527 disorders were monogenic where 57 genes showed pleiotropic effect while single gene mutation is reported for 383 disorders. Of these 527, 363 eye disorders included well-defined ocular phenotypes whereas 380 included systemic phenotypes. 281 disorders associated with 251 genes included both ocular and systemic phenotypes. For the 527 disease units, there were a total of 787 ocular features and 3,094 systemic features, for an average of 2.17 ocular and 8.14 systemic features, respectively, per disease unit. Interestingly, we observed association of atypical systemic features for certain ocular conditions. For example, eye disorders with corneal phenotypes not only show association with typical systemic features like skin and immune responses but cardiovascular and gastrointestinal phenotypes too.
Our work imparts a structure in dissecting genetic eye disorders into unique phenotypes to study the relationship between genes and diseases involving the eye, which can further facilitate novel interpretations of biological mechanisms related to human ocular diseases.
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