Detection by pyrosequencing and prevalence of canine ABCB1 gene mutation nt230 [del4] in sheep dog breeds of Buenos Aires province
DOI:
https://doi.org/10.24215/15142590e019Keywords:
Dogs, P-glycoprotein, neurotoxicity, pyrosequencing, prevalenceAbstract
ABCB1 gene codes for P-glycoprotein (Pgp), a membrane protein that transports multiple drugs out of the cell. It is mainly expressed in the bloodbrain barrier, although it also plays a role in other organs. In dogs, a 4 bp deletion in exon 4 of ABCB1 gene has been reported. This mutation results in a premature stop codon and a nonfunctional protein. Homozygous animals for the deletion present neurotoxicity when administered drugs such as avermectins. This mutation is found mainly in collie, border collie and other related dog breeds. The aim of the present work was to develop a pyrosequencing method for rapid diagnosis of the ABCB1 gene nt230 [del4] mutation and validate it by direct sequencing in a local population. A total of 72 dogs were analyzed, obtaining a 100 % agreement between both methods. The genetic variation of the mutated allele (q) showed differences between the evaluated breeds: collie (n = 30; q = 0.32), border collie (n = 17; q = 0.06), Shetland sheep dog (n=12; q= 0), others (n=13; q = 0). On average, the q value was lower than reported in other countries. Pyrosequencing could be used for early diagnosis of Pgp deficiency, being a very useful tool for controlled reproduction in kennels and for the prevention of neurotoxicity in patients treated with avermectins and other Pgp substrate drugs.
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