[Frontiers in Bioscience 15, 359-372, January 1, 2010]

A decade in search of myopia genes

Felix K. Jacobi1, Carsten M. Pusch2

1Ambulatory Eye Surgery Center, Siemensstrasse 13, D-35394, Giessen, Germany, 2Institute of Anthropology and Human Genetics, Division of Molecular Genetics, University of Tubingen, Wilhelmstrasse 27, D-72074 Tubingen, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Contributions of the environment and genetics
3.1. Environmental factors
3.2. Genetic factors
3.3. The Beaver Dam study
3.4. The GEM study
3.5. Update summary
4. Linkage studies
4.1. Overview
4.2. X-linked loci
4.3. MYP 2 and 3
4.4. Other MYP loci
4.5. Thoughts on linkage approaches
5. Candidate genes
5.1. Overview
5.2. Small leucine-rich repeat proteoglycans
5.3. Nyctalopin
5.4. Transforming growth beta-induced factor (TGIF)
5.5. Hepatocyte growth factor (HGF) and cMET
5.6. Myocilin
5.7. Collagen genes
5.8. PAX6
5.9. Other gene candidates
6. Summary and perspective
7. References

1. ABSTRACT

Nearly half of visual impairment in the world is caused by uncorrected refractive errors, and myopia constitutes a significant proportion of this problem. Moreover, the prevalence of myopia is increasing, especially in Asian countries. Linkage studies have identified at least 18 possible loci (MYP) in 15 different chromosomes associated with myopia, although some of these remain to be confirmed. However, when studies have been carried out to identify specific candidate genes, it is apparent that these genes are often not part of MYP loci. In studying the expression of specific genes that might be responsible for myopia, we are learning that the involvement of various small leucine-rich repeat proteoglycans and growth factors is not a simple one. The emerging picture is one of complex interaction, in which mutations in several genes likely act in concert. The majority of myopia cases are not likely caused by defects in structural proteins, but in defects involving the control of structural proteins. The future of genetic research in this area will likely rely increasingly on microchip array technology.