title: Identification of genetic loci associated with primary angle-closure glaucoma in the basset hound.
abstract: OBJECTIVE
  Primary angle-closure glaucoma (PACG) in dogs is usually caused by the gradual collapse of the iridocorneal angle and cleft, eventually leading to aqueous humor (AH) outflow obstruction. The condition occurs in several breeds of dogs and the prognosis for affected animals is typically poor. We have identified several basset hound (BH) pedigrees, as well as unrelated cases with characteristic PACG that in many aspects recapitulates PACG in human patients. The goal of this study was to utilize the BH PACG model to characterize the genetics of PACG, and potentially discover genetic factors contributing to PACG in humans and animals.
  
  
  METHODS
  We conducted a genome-wide logistic regression test for association using 37 PACG cases and 41 unaffected controls. Population stratification and cryptic relatedness were assessed using a multidimensional scaling analysis. The expression of two candidate genes within the target tissues of the BH eye was assessed by immunohistochemistry.
  
  
  RESULTS
  We report significant associations at two novel loci, specifically BICF2P31912 in COL1A2 on chromosome 14 with a per-allele odds ratio (OR, 95% confidence interval [CI]) of 3.35 (1.73-6.51), P(genome)=3.6×10⁻⁴; and BICF2P893476 residing in proximity to RAB22A on chromosome 24 with a per-allele OR (95% CI) of 3.93 (1.78-8.66), P(genome)=4.9×10⁻⁴. COL1A2 and RAB22A demonstrated widespread expression throughout the eye and were prominently noted in the ciliary body (CB), trabecular meshwork (TM), and iris.
  
  
  CONCLUSIONS
  Our finding of two genetic associations supports the potential segregation of PACG risk-conferring variants in the BH. The genetic associations identified may contribute to mechanisms underlying the pathogenesis of PACG, which remain to be elucidated.
authors.affiliation: Interdisciplinary Graduate Program in Genetics, Iowa City, IA ; Department of Ophthalmology and Visual Sciences, Iowa City, IA.
authors.forename: Dina F
authors.initials: DF
authors.lastname: Ahram
authors.affiliation: Department of Ophthalmology and Visual Sciences, Iowa City, IA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Cook
authors.affiliation: Department of Ophthalmology and Visual Sciences, Iowa City, IA.
authors.forename: Helga
authors.initials: H
authors.lastname: Kecova
authors.affiliation: Animal Eye Consultants of Iowa, North Liberty, Iowa.
authors.forename: Sinisa D
authors.initials: SD
authors.lastname: Grozdanic
authors.affiliation: Interdisciplinary Graduate Program in Genetics, Iowa City, IA ; Department of Ophthalmology and Visual Sciences, Iowa City, IA.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Kuehn
mesh_terms: D000483:Alleles; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015812:Glaucoma, Angle-Closure / Q000235:genetics* / Q000473:pathology / Q000662:veterinary*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics