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https://hdl.handle.net/2440/62339
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Type: | Journal article |
Title: | Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes |
Author: | Dimasi, D. Chen, J. Hewitt, A. Klebe, S. Davey, R. Stirling, J. Thompson, E. Forbes, R. Tan, T. Savarirayan, R. Mackey, D. Healey, P. Mitchell, P. Burdon, K. Craig, J. |
Citation: | Human Genetics, 2010; 127(1):33-44 |
Publisher: | Springer |
Issue Date: | 2010 |
ISSN: | 0340-6717 1432-1203 |
Statement of Responsibility: | David P. Dimasi, Jern Y. Chen, Alex W. Hewitt, Sonja Klebe, Richard Davey, John Stirling, Elizabeth Thompson, Robin Forbes, Tiong Y. Tan, Ravi Savarirayan, David A. Mackey, Paul R. Healey, Paul Mitchell, Kathryn P. Burdon, Jamie E. Craig |
Abstract: | Osteogenesis imperfecta (OI) is a rare connective tissue disorder caused by mutations in the type I collagen genes, COL1A1 and COL1A2, and is characterised by low bone mass and bone fragility. In this study, we explored the relationship between type 1 collagen genes and the quantitative trait central corneal thickness (CCT). CCT was measured in a cohort of 28 Australian type I OI patients and mean CCT was found to be significantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen fibril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was significantly lower in mutant mice (P = 0.002), as was corneal collagen fibril diameter (P = 0.034), whilst collagen fibril density was significantly greater in mutants (P = 0.034). Finally, we conducted a genetic study to determine whether common single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2 are associated with CCT variation in the normal human population. Polymorphism rs2696297 (P = 0.003) in COL1A1 and a three SNP haplotype in COL1A2 (P = 0.007) were all significantly associated with normal CCT variation. These data implicate type 1 collagen in the determination of CCT in both OI patients and normal individuals. This provides the first evidence of quantitative trait loci that influence CCT in a normal population and has potential implications for investigating genes involved in glaucoma pathogenesis, a common eye disease in which the severity and progression is influenced by CCT. |
Keywords: | Cornea Animals Mice, Knockout Humans Mice Osteogenesis Imperfecta Genetic Predisposition to Disease Collagen Collagen Type I Microscopy, Electron Corneal Topography Gene Frequency Genotype Haplotypes Polymorphism, Single Nucleotide Quantitative Trait Loci Australia Female Male Collagen Type I, alpha 1 Chain |
Rights: | © Springer-Verlag 2009 |
DOI: | 10.1007/s00439-009-0729-3 |
Published version: | http://dx.doi.org/10.1007/s00439-009-0729-3 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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