The ABCC4 gene is associated with pyometra in golden retriever dogs

Abstract

Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 × 10–6, passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. Next generation sequencing and genotyping of cases and controls subsequently identified four missense SNPs within the ABCC4 gene. One missense SNP at chr22:45,893,198 (p.Met787Val) showed complete linkage disequilibrium with the associated GWAS SNPs suggesting a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene, is also potentially implicated in the development of the disease.

Tratamento conservador para piometra aberta com aglepristone em matriz reprodutiva premiada da raça Buldogue Francês

“…Em relação a idade da fêmea nos quadros de piometra um fator importante a ser considerado é que animais senis apresentam os casos mais severos da infecção. Isso acontece devido as modificações fisiológicas provenientes do envelhecimento, posicionando este grupo em situações de maior susceptibilidade a evoluírem para o óbito (Jitpean et al, 2012;Hagman, 2018;Arendt et al, 2021). Em contrapartida, animais jovens apresentam influência hormonal (número de ciclos estrais e alterações ovarianas) e a resposta imunológica paulatinamente mais eficazes do que em cadelas senis (Cunha et al, 2020).…”

Drug Discovery in Canine Pyometra Disease Identified by Text Mining and Microarray Data Analysis

“…Therefore, an in-depth study of the key regulatory genes and drug discovery of signaling pathways is of great significance for the diagnosis and treatment of canine pyometra. Meanwhile, bioinformatics, as an emerging discipline, is used to deal with medical data to identify novel diagnosis markers and discover new drugs [12][13][14]. However, to date, no researchers have adopted this method to study the drug discovery of canine pyometra.…”

“…As a variety of research methods for bioinformatics, text mining and microarray data analysis have been applied to the screening of disease biomarkers, the identification of signaling pathways, and the discovery of new drugs [12][13][14][15][16]. At the same time, researchers have found a series of pathogenesis of canine pyometra by doing experiments [17][18][19].…”

Genome wide association study in Swedish Labrador retrievers identifies genetic loci associated with hip dysplasia and body weight

“…Canine genome wide association studies (GWAS) have been proven to be a powerful tool to identify genetic loci associated with both simple and complex inherited conditions in dogs 1 – 3 . Hip dysplasia (HD) occurs commonly in dogs and has a major impact on animal welfare and life expectancy for the affected dogs 4 .…”