title: Analysis of genomic copy number variation in equine recurrent airway obstruction (heaves).
abstract: We explored the involvement of genomic copy number variants (CNVs) in susceptibility to recurrent airway obstruction (RAO), or heaves-an asthmalike inflammatory disease in horses. Analysis of 16 RAO-susceptible (cases) and six RAO-resistant (control) horses on a custom-made whole-genome 400K equine tiling array identified 245 CNV regions (CNVRs), 197 previously known and 48 new, distributed on all horse autosomes and the X chromosome. Among the new CNVRs, 30 were exclusively found in RAO cases and were further analyzed by quantitative PCR, including additional cases and controls. Suggestive association (P = 0.03; corrected P = 0.06) was found between RAO and a loss on chromosome 5 involving NME7, a gene necessary for ciliary functions in lungs and involved in primary ciliary dyskinesia in humans. The CNVR could be a potential marker for RAO susceptibility but needs further study in additional RAO cohorts. Other CNVRs were not associated with RAO, although several involved genes of interest, such as SPI2/SERPINA1 from the serpin gene family, which are associated with chronic obstructive pulmonary disease and asthma in humans. The SPI2/SERPINA1 CNVR showed striking variation among horses, but it was not significantly different between RAO cases and controls. The findings provide baseline information on the relationship between CNVs and RAO susceptibility. Discovery of new CNVs and the use of a larger population of RAO-affected and control horses are needed to shed more light on their significance in modulating this complex and heterogeneous disease.
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.|National Research Centre on Yak (ICAR), Dirang, Arunachal Pradesh, 790101, India.
authors.forename: P J
authors.initials: PJ
authors.lastname: Das
authors.affiliation: Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: McQueen
authors.affiliation: Department of Veterinary Medicine, University of Bern, Bern, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Gerber
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Swiderski
authors.affiliation: Department of Clinical Sciences, University of Montreal, Montreal, QC, J2S 7C6, Canada.
authors.forename: J-P
authors.initials: JP
authors.lastname: Lavoie
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.|New Research Complex, Qatar University, Doha, 2713, Qatar.
authors.forename: B P
authors.initials: BP
authors.lastname: Chowdhary
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: T
authors.initials: T
authors.lastname: Raudsepp
mesh_terms: D000402:Airway Obstruction / Q000235:genetics / Q000662:veterinary*; D000818:Animals; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses / Q000235:genetics*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics
chemical_list: D015843:Serpins
keywords: NME7; SERPINA1; SPI2; array CGH; horse; inflammatory disease; quantitative PCR; whole genome