Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies

Abstract

A frameshift deletion variant in the Wnt pathway gene dishevelled 2 (DVL2) is associated with a truncated, kinked tail (“screw tail”) in English Bulldogs, French Bulldogs and Boston Terriers. These breeds are also characterized by distinctive morphological traits, including a wide head, flat face and short-limbed dwarfism, which are characteristic of Robinow syndrome in humans, caused by defects in genes such as DVL1 and DVL3. Based on these phenotypic and genetic similarities, it has previously been hypothesized that the canine DVL2 variant results in a syndromic phenotype called the Robinow-like syndrome. In our study, we investigated the distribution of the DVL2 variant in 1954 dogs from 15 breeds, identifying breeds with allele variation and enabling the dissection of the genotype–phenotype correlation for the first time. With CT examinations in American Staffordshire Terriers, we confirmed that the DVL2 allele is associated with caudal vertebral malformations and a brachycephalic phenotype. We also hypothesize that the variant may be linked to additional health conditions, including brachycephalic obstructive airway syndrome and congenital heart defects. Altogether, our study strengthens the role of DVL2 as one of the contributors to the “bulldog type” morphology and features on the spectrum of human Robinow syndrome.

Deterministic finite automata for brachycephaly risk estimation in dog

“…There are a few research articles that talk about genetic health issues in dogs, one of these conditions being brachycephaly. In [6] and [5] some of the genes in which mutations are connected with brachycephaly are discussed. In our paper we will consider one of these, the DVL2 gene, for which a genetic primer subsequence is presented in [5].…”

Forensic DNA phenotyping: Canis familiaris breed classification and skeletal phenotype prediction using functionally significant skeletal SNPs and indels

“…The authors also suggest that the derived DVL2 variant may contribute to the extreme brachycephaly seen in the French Bulldog, English Bulldog, and Boston Terrier (Mansour et al, 2018). Recent analysis by the authors of breeds with allele variation at the DVL2 marker confirm this hypothesis (Niskanen et al, 2021). The use of DVL2 as a genetic marker could be somewhat difficult to interpret.…”

“…However, the SMOC2 ‐derived variant cannot reliably be used to predict skull shape as it only accounts for 36% of skull shape variation among domestic dog breeds (Marchant et al, 2017). Conversely, the DVL2 derived variant is thought to decrease hard palate length in a dose‐dependent manner, decrease skull base length in homozygous individuals, decrease the ratio of hard palate to skull base length similarly in homozygous and heterozygous individuals and increase the facial index of homozygous individuals (Niskanen et al, 2021). These features of the skull all contribute to the brachycephalic phenotype (Niskanen et al, 2021).…”

Special issue on companion animal genetics: Novel variants discovered in wide variety of diseases in dogs, identification and further characterization of traits in dogs and cats, and the use of microarrays in the detection of aneuploidy in dogs

“…We were very fortunate to have received several submissions from the prolific canine research laboratory of Hannes Lohi (Niskanen et al 2021;Kyöstilä et al 2021;Kaukonen et al 2021;Hytönen et al 2021a,b). In the first paper, Niskanen et al (2021) investigated the known variant in DVL2 associated with kinked tails and brachycephaly in bulldog breeds in an additional 1954 dogs from 15 breeds.…”

“…We were very fortunate to have received several submissions from the prolific canine research laboratory of Hannes Lohi (Niskanen et al 2021;Kyöstilä et al 2021;Kaukonen et al 2021;Hytönen et al 2021a,b). In the first paper, Niskanen et al (2021) investigated the known variant in DVL2 associated with kinked tails and brachycephaly in bulldog breeds in an additional 1954 dogs from 15 breeds. The researchers confirmed that this deletion variant is associated with caudal vertebral malformations and brachycephaly, and may be involved with brachycephalic obstructive airways and congenital heart defects.…”