Congenital idiopathic megaesophagus in the German shepherd dog is a sex-differentiated trait and is associated with an intronic variable number tandem repeat in Melanin-Concentrating Hormone Receptor 2.

Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus prevent the normal transport of food into the stomach. Affected puppies regurgitate meals and water, fail to thrive, and experience complications such as aspiration pneumonia that may necessitate euthanasia. The German shepherd dog (GSD) has the highest disease incidence, indicative of a genetic predisposition. Here, we discover that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage. A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility. Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM. We describe herein the first genetic factors identified in CIM: sex and a major locus on chromosome 12, which together predict disease state in the GSD with greater than 75% accuracy.

Mortality and morbidity due to gastric dilatation-volvulus syndrome in pedigree dogs in the UK.

OBJECTIVES: To estimate breed-specific risk of death due to, and prevalence of, gastric dilatation-volvulus (GDV) in UK pedigree dogs. METHODS: Data were available on the reported cause of and age at death and occurrence of and age at diagnosis of disease from the 2004 purebred dog health survey. A total of 15,881 dogs of 165 breeds had died in the previous 10 years; GDV was the cause of death in 65 breeds. There were 36,006 live dogs of 169 breeds of which 48 breeds had experienced > or =1 episodes of GDV. Prevalence ratios were used to estimate breed-specific GDV mortality and morbidity risks. RESULTS: Gastric dilatation-volvulus was the cause of death for 389 dogs, representing 2.5% (95% CI: 2.2-2.7) of all deaths reported and the median age at death was 7.92 years. There were 253 episodes in 238 live dogs. The median age at first diagnosis was five years. Breeds at greatest risk of GDV mortality were the bloodhound, Grand Bleu de Gascogne, German longhaired pointer and Neapolitan mastiff. Breeds at greatest risk of GDV morbidity were the Grand Bleu de Gascogne, bloodhound, otterhound, Irish setter and Weimaraner. CLINICAL SIGNIFICANCE: These results suggest that 16 breeds, mainly large/giant, are at increased risk of morbidity/mortality due to GDV.

Proportion of litters of purebred dogs born by caesarean section.

OBJECTIVES: To describe the frequency of caesarean sections in a large sample of pedigree dogs in the UK. METHODS: Data on the numbers of litters born in the previous 10 years were available from a cross-sectional study of dogs belonging to breed club members (2004 Kennel Club/BSAVA Scientific Committee Purebred Dog Health Survey). In this survey 151 breeds were represented with data for households that had reported on at least 10 litters (range 10-14,15): this represented 13,141 bitches which had whelped 22,005 litters. The frequency of caesarean sections was estimated as the percentage of litters that were reported to be born by caesarean section (caesarean rates) and are reported by breed. The dogs were categorised into brachycephalic, mesocephalic and dolicocephalic breeds. RESULTS: The 10 breeds with the highest caesarean rates were the Boston terrier, bulldog, French bulldog, mastiff, Scottish terrier, miniature bull terrier, German wirehaired pointer, Clumber spaniel, Pekingese and Dandie Dinmont terrier. In the Boston terrier, bulldog and French bulldog, the rate was > 80%. CLINICAL SIGNIFICANCE: These data provide evidence for the need to monitor caesarean rates in certain breeds of dog.