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Daniela Gomez-Elizondo, Mariana Lopez-Martinez, Judith Zavala, Jorge E. Valdez-García, Victor Treviño; Novel mutations associated with keratoconus found by a bioinformatic approach . Invest. Ophthalmol. Vis. Sci. 2019;60(9):387. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Despite numerous investigations, the etiology of keratoconus is not well understood but genetical factors have been associated with the disease. Screening the related genetic mutations will allow us to understand its physiopathology in different populations. Nevertheless, few gene panels are available. To collect all reported genes associated to keratoconus, we used a bioinformatic approach to find reported and non-reported mutations that could be used for screening purposes and possible treatment options.
Facilitated by our Pubterm tool, we curated and annotated the genes and PubMed abstracts related to Keratoconus. We used several terms related to genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP), variants, mutations and keratoconus to develop our query. Only human genes were reviewed. We classified them into 8 levels of evidence, such as experimental evidence of mutation, other genetic alterations, negative evidence, genetic alterations in a related diseases and related phenotypes. We consulted our findings in ClinVar from NCBI to corroborate if the sequence variations were already reported as associated with Keratoconus.
Using Pubterm tool, we retrieved 187 abstracts, involving 174 genes. We excluded 8 non-human genes. From the 166 human genes, 56 had genetic alterations; 37 were directly related to Keratoconus, including 11 genes with specific mutations. Besides well know genes such as TGBI and COL4A4, we found 34 genes not related to keratoconus in the public database ClinVar from NCBI.
Our results reveal that there is genetic evidence for at least 37 genes, of which 11 genes shown specific mutations while the rest were related to GWAS markers. Most of them are not annotated in the ClinVar database. We aim to complete a functional analysis of these genes to appreciate the altered signaling pathways which may lead to phenotypic consequences related to keratoconus. These results can be used to suggest a comprehensive genetic panel for screening purposes.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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