Summary Myxomatous mitral valve disease (MMVD) is the most common heart disease and cause of cardiac death in domestic dogs. MMVD is characterised by slow progressive myxomatous degeneration from the tips of the mitral valves onwards with subsequent mitral valve regurgitation, and left atrial and ventricular dilatation. Although the disease usually has a long asymptomatic period, in dogs with severe disease, mortality is typically secondary to left‐sided congestive heart failure. Although it is not uncommon for dogs to survive long enough in the asymptomatic period to die from unrelated causes; a proportion of dogs rapidly advance into congestive heart failure. Heightened prevalence in certain breeds, such as the Cavalier King Charles Spaniel, has indicated that MMVD is under a genetic influence. The genetic characterisation of the factors that underlie the difference in progression of disease is of strong interest to those concerned with dog longevity and welfare. Advanced genomic technologies have the potential to provide information that may impact treatment, prevalence, or severity of MMVD through the elucidation of pathogenic mechanisms and the detection of predisposing genetic loci of major effect. Here we describe briefly the clinical nature of the disorder and consider the physiological mechanisms that might impact its occurrence in the domestic dog. Using results from comparative genomics we suggest possible genetic approaches for identifying genetic risk factors within breeds. The Cavalier King Charles Spaniel breed represents a robust resource for uncovering the genetic basis of MMVD.

Inborn errors of metabolism are genetic conditions that can disrupt intermediary metabolic pathways and cause defective absorption and metabolism of dietary nutrients. In an Australian Kelpie breeding population, 17 puppies presented with intestinal lipid malabsorption. Juvenile dogs exhibited stunted postnatal growth, steatorrhea, abdominal distension and a wiry coat. Using genome-wide association analysis, an associated locus on CFA28 (Praw = 2.87E−06) was discovered and validated in a closely related population (Praw = 1.75E−45). A 103.3 kb deletion NC_006610.3CFA28:g.23380074_23483377del, containing genes Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5) and Zinc Finger DHHC-Type Containing 6 (ZDHHC6), was characterised using whole transcriptomic data. Whole transcriptomic sequencing revealed no expression of ACSL5 and disrupted splicing of ZDHHC6 in jejunal tissue of affected Kelpies. The ACSL5 gene plays a key role in long chain fatty acid absorption, a phenotype similar to that of our affected Kelpies has been observed in a knockout mouse model. A PCR-based diagnostic test was developed and confirmed fully penetrant autosomal recessive mode of inheritance. We conclude the structural variant causing a deletion of the ACSL5 gene is the most likely cause for intestinal lipid malabsorption in the Australian Kelpie.

Plant mating systems shape patterns of genetic diversity and impact the long-term success of populations. As such, they are relevant to the design of seed collections aiming to maximise genetic diversity (e.g., germplasm conservation, ecological restoration). However, for most species, little is known empirically about how variation in mating systems and genetic diversity is distributed. We investigated the relationship between genetic diversity and mating systems in two functionally similar, co-occurring species of Hakea (Proteaceae), and evaluated the extent to which genetic diversity was captured in seeds. We genotyped hundreds of seedlings and mother plants via DArTseq, and developed novel implementations of two approaches to inferring the mating system from SNP data. A striking contrast in patterns of genetic diversity between H. sericea and H. teretifolia was revealed, consistent with a contrast in their mating systems. While both species had mixed mating systems, H. sericea was found to be habitually selfing, while H. teretifolia more evenly employed both selfing and outcrossing. In both species, seed collection schemes maximised genetic diversity by increasing the number of maternal lines and sites sampled, but twice as many sites were needed for the selfing species to capture equivalent levels of genetic variation at a regional scale.

The most common cardiovascular disease in domestic dogs is myxomatous mitral valve disease (MMVD), accounting for 75% of all cardiac disease. An increase in age is generally associated with increased incidence of the disease, but Cavalier King Charles Spaniels (CKCS) exhibit an unusually high prevalence of early-onset MMVD, and thus, potentially greater cardiac morbidity and mortality compared to other breeds. Previous research has suggested that selected candidate risk alleles for MMVD are fixed in CKCSs, including six locations within the Nebulette (NEBL) gene on CFA2. The current study analysed genotypes of 180 Australian CKCSs at the identified risk loci. Of these, 178 were phenotyped for severity of disease by echocardiographic measurements of left atrium to aortic root ratio (LA:Ao) and weight normalised left ventricular end diastolic diameter (LVIDdN). Genotyping array markers correctly predicted the genotype at the risk-variant loci in the CKCS population, and the NEBL1, NEBL2 and NEBL3 variants were observed to be in perfect linkage disequilibrium in this cohort. The CKCS cohort included 6/178 dogs being heterozygous for the protective/wild-type alleles at the NEBL locus. The mean LA:Ao and LVIDdN scores of these dogs heterozygous at NEBL1-3 variants were significantly smaller, and with significantly lower variance compared to age-matched CKCSs that were homozygous for risk alleles. The lower cardiac measurements in the heterozygous dogs indicate a significantly reduced risk of severe MMVD disease. Our analysis suggests that despite relative fixation of the NEBL risk alleles, healthy references alleles at NEBL1-3 exist in low frequency in the CKCS breed and can be used to reduce MMVD severity and mortality.