Companion animals

Contributions from historic popular sires increased recessive disease-causing alleles for two heritable eye conditions in dogs

---

Abstract

In the UK, dog breeding is mainly carried out by numerous small-scale breeders, each contributing a fraction to the overall gene pool. Given the high number of monogenic recessive diseases in pedigree dogs, this study aimed to identify the genetic processes driving changes in the frequencies of two disease-causing alleles over time across five Kennel Club-registered breeds: primary lens luxation (PLL) in the Lancashire Heeler, Sealyham Terrier, and Miniature Bull Terrier and progressive retinal atrophy rod cone degeneration 4 (PRA-rcd4) in the Gordon Setter and Irish Setter. The Royal Kennel Club, UK, provided pedigree information and genetic test results recorded as "clear" (no copies of the disease-causing allele), "carrier" (one copy of the disease-causing allele), or "affected" (two copies of the disease-causing allele) up until 1st January 2025. Across the five pedigrees, census sizes ranged from 6,500 to 74,000 individuals over 52 to 111 years. Genetic tests for PLL or PRA-rcd4 were not introduced until 2010 and 2012, respectively. Hence, the proportion of dogs in each pedigree that underwent genetic testing ranged from 2.6% to 9.3%. First, genotype probabilities were estimated for every individual in each breed using all available genetic test results and pedigree information. Unknown parent groups were assigned to founders based on year of birth and country of origin, and the AlphaPeel software (which applies single-locus iterative peeling) was modified to accommodate these groups. Second, the estimated disease-causing allele frequency trends in each pedigree were partitioned using the R package, AlphaPart, through the accumulation of each individual's Mendelian sampling term (representing their genetic originality) into contributing paths: (1) male and female, (2) female, non-sire males, and each individual sire, (3) before genetic test, not genetically tested, and genetically tested. The Mendelian sampling terms were estimated as the deviation of the individual's estimated disease-causing allele probability from their parents' average probabilities. Results showed that, in all breeds except the Sealyham Terrier, males consistently contributed more to the disease-causing allele frequency than females (path 1). We identified historic popular sires who were, at the time, unknown carriers and contributed to the rapid dissemination of the PRA-rcd4-causing allele in the Irish Setter and Gordon Setter, and of the PLL-causing allele in the Lancashire Heeler (path 2). The high contributions of these sires persist in their descendants today. The more recent decrease in the disease-causing allele frequencies observed in all five breeds can be attributed to the use of genetic testing to inform the mating of clear dogs (path 3). By measuring these contributions, this study offers concrete examples to help dog breeders understand the possible long-term impacts of their mating choices on the occurrence of recessive monogenic diseases.

Keywords: 2026

How to Cite:

Craddock, R., Janes Fistric, M., Mellersh, C., Ilska, J., Wiener, P., Smith, S. & Gorjanc, G., (2026) “Contributions from historic popular sires increased recessive disease-causing alleles for two heritable eye conditions in dogs”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2284765. doi: https://doi.org/10.31274/wcgalp.23613

Rights: 1