Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Apr;292(2):251-269.
doi: 10.1007/s00438-016-1283-z. Epub 2016 Dec 28.

Genomic strategies to understand causes of keratoconus

Justyna A Karolak  1   2 , Marzena Gajecka  3   4
Affiliations
Review

Genomic strategies to understand causes of keratoconus

Justyna A Karolak et al. Mol Genet Genomics. 2017 Apr.

Abstract

Keratoconus (KTCN) is a degenerative disorder of the eye characterized by the conical shape and thinning of the cornea. The abnormal structure of KTCN-affected cornea results in loss of visual acuity. While many studies examine how environmental factors influence disease development, finding the genetic triggers has been a major emphasis of KTCN research. This paper focuses on genomic strategies that were implemented for finding candidate genes, including linkage and association studies, and presents different approaches of mutation screening. The advantages and limitations of particular tools are discussed based on literature and personal experience. Since etiology underlying KTCN is complex, numerous findings indicating heterogeneity of genetic factors involved KTCN etiology are presented.

Keywords: Candidate gene; Complex disease; High-throughput methods; Keratoconus; Next-generation sequencing.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

Justyna A. Karolak and Marzena Gajecka declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by the authors.

Figures

Fig. 1
Fig. 1
Schematic representation of the human eye. a Representation of healthy human eye with normal corneal thickness. b Structure of the human cornea. The cornea is a complex tissue comprised of five main layers (from the anterior to posterior margin): corneal epithelium, Bowman’s membrane, stroma, Descemet’s membrane, and endothelium. c Human eye with keratoconus with characteristic thinning and cone-like bulging of the cornea
Fig. 2
Fig. 2
Integrating biological data from multiple approaches to understand keratoconus. To understand biological processes underlying keratoconus, integrated analysis of various biological aspects may be required. The figure summarizes information on numerous areas, including DNA sequence (genome), epigenetic modifications (epigenome), RNA transcripts (transcriptome), proteins (proteome), metabolites (metabolome), and microorganisms (microbiome). Each element in the array contains examples of techniques and technologies that can be used to study particular biological aspects. List of abbreviations: genome-wide association study (GWAS), next-generation sequencing (NGS), whole-genome sequencing (WGS), whole-exome sequencing (WES), reverse-transcription-PCR (RT-PCR), chromatin immunoprecipitation-sequencing (ChIP-Seq), RNA sequencing (RNA-seq), whole-genome bisulfite sequencing (WGB-seq), 2-D gel electrophoresis (2-DE), enzyme-linked immunosorbent assay (ELISA), nuclear magnetic resonance (NMR), mass spectrometry (MS), gas chromatography (GC), liquid chromatography–mass spectrometry (LC–MS)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abu A, Frydman M, Marek D, et al. Deleterious mutations in the Zinc-Finger 469 gene cause brittle cornea syndrome. Am J Hum Genet. 2008;82:1217–1222. doi: 10.1016/j.ajhg.2008.04.001. - DOI - PMC - PubMed
    1. Abu-Amero KK, Kalantan H, Al-Muammar AM. Analysis of the VSX1 gene in keratoconus patients from Saudi Arabia. Mol Vis. 2011;17:667–672. - PMC - PubMed
    1. Abu-Amero KK, Azad TA, Kalantan H, et al. Mitochondrial sequence changes in keratoconus patients. Invest Ophthalmol Vis Sci. 2014;55:1706–1710. doi: 10.1167/iovs.14-13938. - DOI - PubMed
    1. Abu-Amero KK, Helwa I, Al-Muammar A, et al. Case-control association between CCT-associated variants and keratoconus in a Saudi Arabian population. J Negat Results Biomed. 2015;14:10. doi: 10.1186/s12952-015-0029-5. - DOI - PMC - PubMed
    1. Abu-Amero KK, Helwa I, Al-Muammar A, et al. Screening of the seed region of MIR184 in keratoconus patients from Saudi Arabia. BioMed Res Int. 2015;2015:604508. doi: 10.1155/2015/604508. - DOI - PMC - PubMed