Journal article
Identification of genetic loci associated with primary angle-closure glaucoma in the basset hound
Molecular vision, Vol.20, pp.497-510
2014
PMCID: PMC4000717
PMID: 24791135
Abstract
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. 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. 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. 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.
Details
- Title: Subtitle
- Identification of genetic loci associated with primary angle-closure glaucoma in the basset hound
- Creators
- Dina F Ahram - Interdisciplinary Graduate Program in Genetics, Iowa City, IA ; Department of Ophthalmology and Visual Sciences, Iowa City, IAAmy C Cook - Department of Ophthalmology and Visual Sciences, Iowa City, IAHelga Kecova - Department of Ophthalmology and Visual Sciences, Iowa City, IASinisa D Grozdanic - Animal Eye Consultants of Iowa, North Liberty, IowaMarkus H Kuehn - Interdisciplinary Graduate Program in Genetics, Iowa City, IA ; Department of Ophthalmology and Visual Sciences, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Molecular vision, Vol.20, pp.497-510
- Publisher
- United States
- PMID
- 24791135
- PMCID
- PMC4000717
- ISSN
- 1090-0535
- eISSN
- 1090-0535
- Grant note
- R01 EY019485 / NEI NIH HHS R01 EY022044 / NEI NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980282302771
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