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Home / Equine Research Bank / Int J Genomics / Additional Evidence for DDB2 T338M as a Genetic Risk Factor ...
International journal of genomics2019; 2019; 3610965; doi: 10.1155/2019/3610965

Additional Evidence for DDB2 T338M as a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Horses.

Abstract: Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC cases were genotyped for the DDB2 variant and associations were investigated. Horses with urogenital SCC that were heterozygous for the DDB2 risk allele were identified in the Appaloosa breed, but a significant association between the DDB2 variant and SCC occurring at any location in this breed was not detected. The risk allele was not identified in Arabians, and no Percherons were homozygous for the risk allele. High-throughput sequencing data from six Haflingers were analyzed to ascertain if any other variant from the previously associated 483 kb locus on ECA12 was more concordant with the SCC phenotype than the DDB2 variant. Sixty polymorphisms were prioritized for evaluation, and no other variant from this locus explained the genetic risk better than the DDB2 allele (P = 3.39 × 10-17, n = 118). These data provide further support of the DDB2 variant contributing to risk for ocular SCC, specifically in the Haflinger and Belgian breeds.
Copyright © 2019 Moriel H. Singer-Berk et al.
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Publication Date: 2019-09-15 PubMed ID: 31637255PubMed Central: PMC6766160DOI: 10.1155/2019/3610965Google 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.

The study is focused on confirming a genetic mutation (DDB2 T338M) as a major risk factor for squamous cell carcinoma (SCC), a common ocular cancer in horses, specifically in Haflinger and Belgian breeds.

Overview of the Study

  • The research is primarily an exploration of a previously identified genetic mutation in the damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met). This mutation was initially found to be significantly associated with ocular squamous cell carcinoma (SCC) in Haflinger and Belgian breeds of horses.
  • The researchers aimed to confirm whether the same genetic variant increased the risk for ocular SCC in Arabian, Appaloosa, and Percheron breeds. Further, it was investigated whether this genetic variant contributed to the risk for oral or urogenital SCC.
  • The research was carried out by genotyping histologically confirmed SCC cases for the DDB2 variant and investigating the associations.

Key Findings

  • The study identified Appaloosa horses with urogenital SCC that were heterozygous for the DDB2 risk allele. However, no significant association could be detected between the DDB2 variant and SCC occurring at any location in this breed.
  • The research found that the risk allele was not present in Arabians and no Percherons were homozygous for the risk allele.
  • To determine if there were potentially other concordant genetic variants responsible for SCC, high-throughput sequencing data from six Haflingers were analysed.
  • A total of sixty polymorphisms were evaluated from a previously associated 483 kb locus on ECA12, a genome position. The analysis concluded that no other variant from this locus explained the genetic risk better than the DDB2 allele (P = 3.39 × 10-17, n = 118).

Conclusions

  • The findings of this research validate the previous understanding that the DDB2 variant plays a significant part in risk for ocular SCC in horses, specifically in the Haflinger and Belgian breeds.
  • Furthermore, the study goes on to provide evidence that this DDB2 variant is the main genetic risk better than any other genetic variant in the 483 kb locus on ECA12.
  • However, the study indicates that presence of this variant does not mean an increased risk of SCC in all breeds, and its impact might be limited to certain specific breeds.

Cite This Article

APA
Singer-Berk MH, Knickelbein KE, Lounsberry ZT, Crausaz M, Vig S, Joshi N, Britton M, Settles ML, Reilly CM, Bentley E, Nunnery C, Dwyer A, Lassaline ME, Bellone RR. (2019). Additional Evidence for DDB2 T338M as a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Horses. Int J Genomics, 2019, 3610965. https://doi.org/10.1155/2019/3610965

Publication

International journal of genomics
ISSN: 2314-4378
NlmUniqueID: 101605206
Country: United States
Language: English
Volume: 2019
Pages: 3610965

Researcher Affiliations

Singer-Berk, Moriel H
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Knickelbein, Kelly E
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
  • Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA 95616, USA.
Lounsberry, Zachary T
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Crausaz, Margo
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Vig, Savanna
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Joshi, Nikhil
  • Bioinformatics Core Facility, Genome Center, University of California-Davis, Davis, CA 95616, USA.
Britton, Monica
  • Bioinformatics Core Facility, Genome Center, University of California-Davis, Davis, CA 95616, USA.
Settles, Matthew L
  • Bioinformatics Core Facility, Genome Center, University of California-Davis, Davis, CA 95616, USA.
Reilly, Christopher M
  • Insight Veterinary Specialty Pathology, Davis, CA, USA.
Bentley, Ellison
  • Department of Surgical Services, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Nunnery, Catherine
  • School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dwyer, Ann
  • Genesee Valley Equine Clinic, Scottsville, NY 14546, USA.
Lassaline, Mary E
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Bellone, Rebecca R
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.

Conflict of Interest Statement

Rebecca R. Bellone and Zachary T. Lounsberry are affiliated with the Veterinary Genetics Laboratory, which offers genetic diagnostic testing in horses.

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Citations

This article has been cited 5 times.
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