title: Copy number variation in the horse genome.
abstract: We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Pranab J
authors.initials: PJ
authors.lastname: Das
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Erica
authors.initials: E
authors.lastname: Fang
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Rytis
authors.initials: R
authors.lastname: Juras
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
authors.forename: E Gus
authors.initials: EG
authors.lastname: Cothran
authors.affiliation: New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Pennsylvania, United States of America.
authors.forename: Sue
authors.initials: S
authors.lastname: McDonell
authors.affiliation: Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Kenney
authors.affiliation: M.H. Gluck Equine Research Center, Veterinary Science Department, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Teri L
authors.initials: TL
authors.lastname: Lear
authors.affiliation: School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Adelson
authors.affiliation: New Research Complex, Qatar University, Al Tarfa, Doha, Qatar.
authors.forename: Bhanu P
authors.initials: BP
authors.lastname: Chowdhary
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Terje
authors.initials: T
authors.lastname: Raudsepp
mesh_terms: D015089:20-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001947:Breeding; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D016678:Genome; D006736:Horses / Q000235:genetics*; D006801:Humans
chemical_list: D015089:20-Hydroxysteroid Dehydrogenases