Polymorphisms in the canine monoamine oxidase a (MAOA) gene: identification and variation among five broad dog breed groups

Abstract

Background: In humans, reduced activity of the enzyme monoamine oxidase type A (MAOA) due to genetic polymorphisms within the MAOA gene leads to increased brain neurotransmitter levels associated with aggression. In order to study MAOA genetic diversity in dogs, we designed a preliminary study whose objectives were to identify novel alleles in functionally important regions of the canine MAOA gene, and to investigate whether the frequencies of these polymorphisms varied between five broad breed groups (ancient, herding, mastiff, modern European, and mountain). Fifty dogs representing these five breed groups were sequenced.

Results: A total of eleven polymorphisms were found. Seven were single nucleotide polymorphisms (SNPs; two exonic, two intronic and three in the promoter), while four were repeat intronic variations. The most polymorphic loci were repeat regions in introns 1, 2 (7 alleles) and 10 (3 alleles), while the exonic and the promoter regions were highly conserved. Comparison of the allele frequencies of certain microsatellite polymorphisms among the breed groups indicated a decreasing or increasing trend in the number of repeats at different microsatellite loci, as well as the highest genetic diversity for the ancient breeds and the lowest for the most recent mountain breeds, perhaps attributable to canine domestication and recent breed formation. While a specific promoter SNP (-212A > G) is rare in the dog, it is the major allele in wolves. Replacement of this ancestral allele in domestic dogs may lead to the deletion of heat shock factor binding sites on the MAOA promoter.

Conclusions: Dogs exhibit significant variation in certain intronic regions of the MAOA gene, while the coding and promoter regions are well-conserved. Distinct genetic differences were observed between breed groups. Further studies are now required to establish whether such polymorphisms are associated in any way with MAOA level and canine behaviour including aggression.

Keywords: Aggression; Breed difference; Canine; MAOA; Polymorphism.

Fig. 1

Overall genomic structure and sequencing strategy for the canine MAOA gene. Legend: The arrangement of exons is shown relative to the scale provided at the top, which corresponds to the most recent version of the canine genome assembly, canFam3 (available at: https://genome.ucsc.edu/cgi-bin/hgGateway). The position of each of the 7 target regions is indicated by the numbered circles. 1: promoter and exon 1; 2: SINEC_Cf in intron 1; 3: intron 2 repeat region; 4: exons 7 and 8; 5: Intron 10 repeat regions; 6: exon 12; 7: exon 15 and 3′UTR

Fig. 2

Gene map displaying MAOA polymorphisms

Fig. 3

Minor Allele Frequencies (MAF) for the MAOA intron 1 TTTA variants across canine breed groups (n = 10 for each group)