title: Genetic Evidence for Differential Regulation of Corneal Epithelial and Stromal Thickness.
abstract: OBJECTIVE
  Central corneal thickness (CCT) is a quantitative trait associated with keratoconus and primary open-angle glaucoma. Although CCT is highly heritable, known genetic variations explain only a fraction of the phenotypic variability. The purpose of this study was to identify additional CCT-influencing loci using inbred strains of mice.
  
  
  METHODS
  Cohorts of 82 backcrossed (N2) and 99 intercrossed (F2) mice were generated from crosses between recombinant inbred BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical coherence tomography, mice were phenotyped at 10 to 12 weeks of age, genotyped based on 96 genome-wide single nucleotide polymorphisms (SNPs), and subjected to quantitative trait locus (QTL) analysis.
  
  
  RESULTS
  In an analysis of total CCT among all mice, two loci passed the significance threshold of P = 0.05. These were on Chr 3 and Chr 11 (Cctq4 and Cctq5, respectively). A third locus of interest was identified in a two-dimensional pairwise analysis; this locus on Chr 14 (Cctq6) exhibited a significant additive effect with Cctq5. Independent analyses of the dataset for epithelial and stromal thickness revealed that Cctq4 is specific to the epithelial layer and that Cctq5 and Cctq6 are specific to the stromal layer.
  
  
  CONCLUSIONS
  Our findings demonstrate a quantitative multigenic pattern of CCT inheritance in mice and identify three previously unrecognized CCT-influencing loci: Cctq4, Cctq5, and Cctq6. This is the first demonstration that distinct layers of the cornea are under differential genetic control and highlights the need to refine the design of future genome-wide association studies of CCT.
authors: Department of Molecular Physiology and Biophysics University of Iowa, Iowa City, Iowa, United States.
authors: Demelza R
authors: DR
authors: Koehn
authors: Department of Molecular Physiology and Biophysics University of Iowa, Iowa City, Iowa, United States.
authors: Kacie J
authors: KJ
authors: Meyer
authors: Department of Molecular Physiology and Biophysics University of Iowa, Iowa City, Iowa, United States 2Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States 3Center for the Prevention and Treatment of Visual Lo.
authors: Michael G
authors: MG
authors: Anderson
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D063171:Corneal Pachymetry; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci