TY - JOUR

T1 - Evaluation of the value of genetic testing for cystinuria in the Danish population of English bulldogs

AU - Fitzwilliams, Therese

AU - Wolff-Sneedorff, Julie L.

AU - Fredholm, Merete

AU - Karlskov-Mortensen, Peter

AU - Guldbrandtsen, Bernt

AU - Bruun, Camilla S.

N1 - Publisher Copyright: © 2023 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

PY - 2023

Y1 - 2023

N2 - Cystinuria is a genetic disease that can lead to cystine urolith formation. The English bulldog is the dog breed most frequently affected. In this breed, three missense mutations have been suggested to be associated with cystinuria: c.568A>G and c.2086A>G in SLC3A1 and c.649G>A in SLC7A9. In this study, the occurrence of these three mutations in the Danish population of English bulldogs was investigated. Seventy-one English bulldogs were genotyped using TaqMan assays. The dogs’ owners were given questionnaires concerning the medical histories of their dogs. Allele frequencies of 0.40, 0.40, and 0.52 were found for the mutant alleles in the three loci: c.568A>G, c.2086A>G, and c.649G>A, respectively. For both mutations in SLC3A1, a statistically significant association was found between cystinuria and homozygosity for the G allele among male, English bulldogs. For the mutation in SLC7A9, there was no statistically significant association between homozygosity for the mutant allele and cystinuria. Due to high allele frequencies, limited genetic diversity, continued uncertainty about the genetic background of cystinuria, and more severe health problems in the breed, selection based on genetic testing for the mutations in SLC3A1 cannot be recommended in the Danish population of English bulldogs. However, results of the genetic test may be used as a guide to recommend prophylactic treatment.

AB - Cystinuria is a genetic disease that can lead to cystine urolith formation. The English bulldog is the dog breed most frequently affected. In this breed, three missense mutations have been suggested to be associated with cystinuria: c.568A>G and c.2086A>G in SLC3A1 and c.649G>A in SLC7A9. In this study, the occurrence of these three mutations in the Danish population of English bulldogs was investigated. Seventy-one English bulldogs were genotyped using TaqMan assays. The dogs’ owners were given questionnaires concerning the medical histories of their dogs. Allele frequencies of 0.40, 0.40, and 0.52 were found for the mutant alleles in the three loci: c.568A>G, c.2086A>G, and c.649G>A, respectively. For both mutations in SLC3A1, a statistically significant association was found between cystinuria and homozygosity for the G allele among male, English bulldogs. For the mutation in SLC7A9, there was no statistically significant association between homozygosity for the mutant allele and cystinuria. Due to high allele frequencies, limited genetic diversity, continued uncertainty about the genetic background of cystinuria, and more severe health problems in the breed, selection based on genetic testing for the mutations in SLC3A1 cannot be recommended in the Danish population of English bulldogs. However, results of the genetic test may be used as a guide to recommend prophylactic treatment.

KW - breeding recommendations

KW - COLA transporter defect

KW - cystine crystalluria

KW - cystine urolithiasis

KW - English bulldog

U2 - 10.1111/age.13321

DO - 10.1111/age.13321

M3 - Journal article

C2 - 36971195

AN - SCOPUS:85151410040

VL - 54

SP - 566

EP - 569

JO - Animal Genetics

JF - Animal Genetics

SN - 0268-9146

IS - 4

ER -