DNA Sequence Variants in the Five Prime Untranslated Region of the Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves

Abstract

The aim of this study was to investigate the frequency of regional DNA variants upstream to the translation initiation site of the canine Cyclooxygenase-2 (Cox-2) gene in healthy dogs. Cox-2 plays a role in various disease conditions such as acute and chronic inflammation, osteoarthritis and malignancy. A role for Cox-2 DNA variants in genetic predisposition to canine renal dysplasia has been proposed and dog breeders have been encouraged to select against these DNA variants. We sequenced 272-422 bases in 152 dogs unaffected by renal dysplasia and found 19 different haplotypes including 11 genetic variants which had not been described previously. We genotyped 7 gray wolves to ascertain the wildtype variant and found that the wolves we analyzed had predominantly the second most common DNA variant found in dogs. Our results demonstrate an elevated level of regional polymorphism that appears to be a feature of healthy domesticated dogs.

Fig 1. DNA sequence variants identified within the 5’UTR of the Cox-2 gene in 152 dogs.

Base positions upstream of the ATG translation initiation site (position zero) are noted on the left. *The exact base position for the duplicated sequence could not be determined. The sequence variant most commonly found in gray wolves is boxed.

Fig 2. Alignment of DNA sequences upstream of the ATG of the Cox-2 gene from Human, Horse, Cow, Wolf, CanFam3.1 assembly, Mouse and Chicken.

The presumed translation initiation ATG is boxed. A DNA variant (deletion of 12 nucleotides) is observed in CanFam3.1 sequence when compared to other organisms (double headed arrow).