Genetic investigation of equine recurrent uveitis in Appaloosa horses

H. Rockwell, M. Mack, T. Famula, L. Sandmeyer, B. Bauer, A. Dwyer, M. Lassaline, S. Beeson, S. Archer, M. McCue, R. R. Bellone

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low-grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome-wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10−5, P = 5.91 × 10−6, P = 4.91 × 10−5, P = 6.46 × 10−5). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10−5). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU.

Original languageEnglish (US)
Pages (from-to)111-116
Number of pages6
JournalAnimal Genetics
Volume51
Issue number1
DOIs
StatePublished - Feb 1 2020

Bibliographical note

Funding Information:
H. Rockwell M. Mack T. Famula L. Sandmeyer B. Bauer A. Dwyer M. Lassaline S. Beeson S. Archer M. McCue R. R. Bellone rbellone@ucdavis.edu Veterinary Genetics Laboratory Department of Population Health and Reproduction School of Veterinary Medicine University of California – Davis Davis 95616 CA USA Appaloosa Project Davis 95616 CA USA Department of Small Animal Clinical Sciences Western College of Veterinary Medicine University of Saskatchewan Saskatoon SK S7N 5B4 Canada Genesee Valley Equine Clinic LLC Scottsville NY 14546 USA Department of Radiological and Surgical Sciences School of Veterinary Medicine University of California – Davis Davis CA 95616 USA Veterinary Population Medicine Department College of Veterinary Medicine University of Minnesota St Paul MN 55108 USA Appaloosa Project Sayward V0P 1R0 BC Canada Appaloosa depigmentation genome‐wide association study horse recurrent uveitis Townsend Equine Health Research Fund (TEHRF) Morris Animal Foundation D16EQ‐028 Table S1 SNPs reaching genome‐wide suggestive significance for association with ERU based on three mixed model analyses. Table S2 Top‐ranked SNPs reaching suggestive significance ( P  < 1.0 × 10 −4 ) for association with ERU risk and their respective candidate genes. Table S3 Functions and disease phenotypes of positional candidate genes identified from associated SNPs. Table S4 Logistic regression analysis performed to model ERU risk in cohort 2. Table S5 Logistic regression analysis to analyze the dependence of ERU risk on the extent of varnish roaning in a subset of 48 horses from cohort 2. Figure S1 Equine recurrent uveitis in the Appaloosa. Figure S2 LP and PATN1 coat patterning in Appaloosas. Figure S3 LP‐ induced varnish roaning. Figure S4 Manhattan plots of multiple mixed linear model analyses using LP and age as covariates. Figure S5 Receiver operating characteristic (ROC) curve for the logistic regression model containing terms for LP genotype, PATN1 genotype, and age in predicting ERU risk. Appendix S1 Supplemental statistical methods for logistic regression analyses in population 2. Appendix S2 Supplemental methods for varnish roan phenotyping.

Funding Information:
The authors gratefully acknowledge Dr Stephanie Valberg, Dr Heather Kaese, Dr James Mickelson, Dr Mark Rutherford, Dr Adrienne Williams and Anna Dahlgren for their technical assistance and contributions to this project. We thank the horse owners who allowed their animals to be examined and participate in this study. This study was made possible with support from the Townsend Equine Health Research Fund (TEHRF) and the Morris Animal Foundation D16EQ‐028. The mission of the Morris Animal Foundation is to bridge science and resources to advance the health of animals. Rebecca R. Bellone is affiliated with the Veterinary Genetics Laboratory, a laboratory offering diagnostic tests in horses.

Funding Information:
The authors gratefully acknowledge Dr Stephanie Valberg, Dr Heather Kaese, Dr James Mickelson, Dr Mark Rutherford, Dr Adrienne Williams and Anna Dahlgren for their technical assistance and contributions to this project. We thank the horse owners who allowed their animals to be examined and participate in this study. This study was made possible with support from the Townsend Equine Health Research Fund (TEHRF) and the Morris Animal Foundation D16EQ-028. The mission of the Morris Animal Foundation is to bridge science and resources to advance the health of animals. Rebecca R. Bellone is affiliated with the Veterinary Genetics Laboratory, a laboratory offering diagnostic tests in horses.

Keywords

  • Appaloosa
  • depigmentation
  • genome-wide association study
  • horse
  • recurrent uveitis

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