Analysis of Keratoconus genetic factors within Keratoconus Loci and mtDNA

Purpose Keratoconus (KTCN) is a multifactorial disorder in which both environmental and genetic factors are involved. Genetic studies have led to the identification of several loci on different chromosomes, linked to KTCN. However, only few reports indicated causative genes in these loci. The aim of...

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Bibliographic Details
Published in:Acta ophthalmologica (Oxford, England) England), 2014-09, Vol.92 (s253), p.0-0
Main Authors: NOWAK, DM, KAROLAK, JA, KUBICKA, M, KULINSKA, K, POLAKOWSKI, P, SZAFLIK, JP, GAJECKA, M
Format: Article
Language:English
Subjects:
Genes
Genomes
Mitochondrial DNA
Ophthalmology
Online Access:Get full text
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Summary:Purpose Keratoconus (KTCN) is a multifactorial disorder in which both environmental and genetic factors are involved. Genetic studies have led to the identification of several loci on different chromosomes, linked to KTCN. However, only few reports indicated causative genes in these loci. The aim of this project was to analyze the DNA sequence information available in the databases of SNVs located within known KTCN loci. We extended the analyzes to include miRNA genes located. Additionally, sequencing of mitochondrial genome in KTCN patients from Polish population was performed. Methods The list of SNVs, which are located in KTCN loci were obtained on the basis of Ensemble. For analyzed SNVs allele frequencies were obtained from 1,000 Genomes Project. The list of miRNA genes was obtained from the miRBase. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen and SIFT. Additionally, mtDNA was analyzed in samples from 93 people with the Polish population (42 ‐ KTCN, 51 – controls). Results In this study 94 miRNA‐encoding genes and over 2 million SNVs were identified within known KTCN loci. From these SNVs, over 4,500 were located within exons and almost 600 SNVs were indicated as deleterious. Sequencing analysis of fragments of the mitochondrial genome revealed a number of changes, including several new polymorphisms. Conclusion The KTCN development does not depend on a single change in the gene, but on the accumulation of numerous sequence variants. The complexity of KTCN etiology causes the need to find appropriate approach to investigate this disease. Support: National Science Centre, Poland, grant no. 2011/03/N/NZ5/01470
ISSN:1755-375X
1755-3768
DOI:10.1111/j.1755-3768.2014.1766.x