Analysis of PDK4 gene deletion in a population of Doberman Pinschers from Argentina

PR BATISTA; M CZERNIGOW; A ARIZMENDI; MR VERCELLINI; G GIOBAMBATTISTA; J CRESPI; DO ARIAS

Barcelona

Congreso; ECVIM-CA Congress 2020; 2020

European College of Veterinary Internal Medicine

Dilated cardiomyopathy (DCM) in Doberman Pinschers (DP) is a polygenic disease inherited as an autosomal dominant trait with incomplete penetrance. In American DP, DCMdevelopment has been associated with a 16-bp deletion in the 5′ splice site of intron 10 of the pyruvate dehydrogenase kinase, isozyme 4 (PDK4) gene on chromosome 14.However, such association has not been observed in European DP. The aim of this study was to estimate the prevalence of PDK4 16bp INDEL variant and determine its associationwith DCM in a DP cohort from Argentina.A total of 134 DP (58 male and 76 female) aged 4?15 years were assessed to evaluate the prevalence of the 16 bp deletion allele. For the association study, dogs were allocatedinto two groups: 1) DCM (n=20, ≥4 years old, left ventricle diastolic diameter ≥49 mm and left ventricle systolic diameter ≥42 mm), and 2) control (n=45, ≥7 years old, without clinical,electrical or morphological findings). The remaining 69 DP were not included because they did not comply with the inclusion criteria. According to the reported variant in the PDK4gene (CFA14: g.20,829,667_20,829,682del; genome build CanFam 3.1), primers were designed to amplify a fragment that included the INDELs (forward primer, 5′-GTTTTGGTTATGGCTTACCAATT-3′ and reverse primer, 5′-ATGGACTCTCTCTCTCTCAAATA-3′). Amplicons of 210-bp for the wild type (ins) and 194-bp for the variant (del) allele wereobtained with polymerase chain reaction (PCR). The genotype of each animal was determined in a 1% agarose electrophoresis gel. Finally, the fragments obtained were sequencedwith ABI 3500 Genetic Analyzer (Applied Biosystems). The prevalence of the variant allele and its association with DCM development were evaluated using a Fisher´s Exact Test withthe odds ratio function of the R epitools package. p