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PLoS genetics2014; 10(10); e1004712; doi: 10.1371/journal.pgen.1004712

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.
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Publication Date: 2014-10-23 PubMed ID: 25340504PubMed Central: PMC4207638DOI: 10.1371/journal.pgen.1004712Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper discusses a study that investigated variations in the number of copies of genes (referred to as copy number variations or CNVs) in the genome of horses, including several different breeds and Przewalski horses. The team reports on 258 CNV regions, the presence of CNVs in relation to different breeds, and the potential relationship of these CNVs to certain genetic disorders in horses.

Research Methodology

  • The researchers constructed a 400K Whole-Genome (WG) tiling oligoarray specific for the horse genome. An oligoarray is a microarray where each spot contains a small amount (25-60 bases) of DNA or RNA.
  • This oligoarray was used for the discovery of CNVs in a selection of 38 normal horses from 16 diverse breeds, as well as the Przewalski horse, which is considered to be a close relative of the domestic horse.
  • The probes on this array represented not only genes (autosomal and X-linked) but also intergenic, sub-telomeric, and chrY sequences.

Findings

  • The team identified a total of 258 CNV regions (CNVRs) spread across all autosomes, the X chromosome (chrX), and unknown sequences (chrUn), except the Y chromosome (chrY).
  • In total, CNVs make up 1.3% of the total horse genome with chromosome 12 being the most enriched.
  • Among the studied breeds, American Miniature horses showed the highest degree of CNVs while American Quarter Horses showed the lowest, when compared to a Thoroughbred reference.
  • The Przewalski horse was found to be similar to native ponies and draft horse breeds in terms of CNVs.
  • Of the identified CNVRs, the majority involved genes while 20% were located in regions between genes known as intergenic regions.
  • Pertaining to the molecular function of CNV-associated genes, the predominant roles lay in sensory perception, immunity, and reproduction.
  • A composite genome-wide dataset of 1476 CNVRs was created by combining these findings with previous studies.

Implications and Conclusions

  • Out of these 1476 CNVRs, 301 were shared between multiple studies, while 1174 were considered novel and require further validation.
  • To this date, 41 out of over 400 horse breeds have been scrutinized for CNVs, with 11 new breeds added in this particular study.
  • The CNV data collected was used in a pilot study for investigating CNVs in 6 horses with XY disorders of sexual development. A deletion involving AKR1C gene cluster in chromosome 29 was potentially causative due to AKR1C genes’ known role in testicular androgen synthesis and sexual development.
  • The study highlights the need to analyze more breeds and individuals using similar methodology for an effective discovery of biomedical variants of importance.

Cite This Article

APA
Ghosh S, Qu Z, Das PJ, Fang E, Juras R, Cothran EG, McDonell S, Kenney DG, Lear TL, Adelson DL, Chowdhary BP, Raudsepp T. (2014). Copy number variation in the horse genome. PLoS Genet, 10(10), e1004712. https://doi.org/10.1371/journal.pgen.1004712

Publication

PLoS genetics
ISSN: 1553-7404
NlmUniqueID: 101239074
Country: United States
Language: English
Volume: 10
Issue: 10
Pages: e1004712

Researcher Affiliations

Ghosh, Sharmila
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
Qu, Zhipeng
  • School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
Das, Pranab J
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
Fang, Erica
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
Juras, Rytis
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
Cothran, E Gus
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
McDonell, Sue
  • New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Pennsylvania, United States of America.
Kenney, Daniel G
  • Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Lear, Teri L
  • M.H. Gluck Equine Research Center, Veterinary Science Department, University of Kentucky, Lexington, Kentucky, United States of America.
Adelson, David L
  • School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
Chowdhary, Bhanu P
  • New Research Complex, Qatar University, Al Tarfa, Doha, Qatar.
Raudsepp, Terje
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.

MeSH Terms

  • 20-Hydroxysteroid Dehydrogenases / genetics
  • Animals
  • Base Sequence
  • Breeding
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations / genetics
  • Genome
  • Horses / genetics
  • Humans

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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