Heterozygosity testing and multiplex DNA panel screening as a potential tool to monitor health and inbreeding in a small, closed dog population

Abstract

Background: Selective breeding in populations with a limited effective population size may result in a loss of genetic diversity, which can cause an increased concentration of specific disease liability genes. The Dutch Shepherd Dog (DSD) in the Netherlands is an example of such a breed with a small effective population.

Objective: To evaluate the measurement of genetic diversity and multiplex DNA panel screening for implementation in a breeding strategy for the Dutch Shepherd Dog (DSD) and to investigate the clinical relevance of potentially identified mutations in the multiplex DNA panel screening.

Results: Genome-wide SNP testing showed genetic isolation and reduced genetic diversity within coat variety subgroups of the DSD. Panel screening identified a Von Willebrand's Disease type I mutation. Although decreased Von Willebrand's Factor proteins were significantly lower in DSDs carrying the VWD-I allele compared to the wildtype, clinical follow-up did not show a significant association between the clinical phenotype and VWD-I genotype.

Conclusions: Genetic relationship measurement within a breed population may be a useful tool to enable breeding strategies to conserve genetic diversity. Results from a disease panel screening need to be evaluated for clinical relevance before breed selection restrictions can be considered.

Keywords: Canine health; Dog breeding; Dutch shepherd dog; Genetic disorder; Heterozygosity; MyDogDNA™; Von Willebrand’s disease.

Fig. 1

Genetic relationship and diversity in the Dutch Shepherd Dog. a Crossbreeding of short haired and long haired Dutch Shepherd Dogs. Parent populations of short haired (green) and long haired (red) dogs were matched to produce first generation variety crosses. Matching variety crosses with a parent population (backcross) resulted in the next generation of variety crosses. b Genetic relationship of the tested population of Dutch Shepherd Dogs in a multidimensional scaling plot. The parent populations shown are short haired (green, n = 13), long haired (red, n = 28), and wire haired (blue, n = 13) varieties. Variety crosses are shown in the colour of the genetically confirmed coat variety (trait testing MyDogDNA™). c Genetic diversity of the tested population of Dutch Shepherd Dogs. The short haired (green, n = 18), long haired (red, n = 46), and wire haired (blue, n = 16) are shown together with a combination of the variety crosses between long and short haired (black, n = 25)

Fig. 2

Von Willebrand’s Factor mutation analysis. Example of chromosomal DNA containing Von Willebrand’s Factor c.7437G > A. WT = wildtype, HET = heterozygous carrier, MUT = homozygous mutant

Fig. 3

Von Willebrand’s Disease segregation in the Dutch Shepherd Dog. Dutch Shepherd Dog pedigree following first identification (*) of a carrier of Von Willebrand’s Disease type I. This individual was a female long haired shepherd born in 2010.

Fig. 4

Von Willebrand’s Factor protein concentration and genotype correlation in the Dutch Shepherd Dog. Correlation between Von Willebrand’s Factor protein concentrations in blood (median shown in red) and Von Willebrand’s Disease genotype (G/G = wildtype (n = 9), G/A = heterozygous carrier (n = 8), A/A = homozygous mutant (n = 2)), in 19 Dutch Shepherd Dogs. No significant difference in protein concentration was found when the three groups were compared (Kruskal-Wallis test, p = 0.07). Comparing the wildtype group with the other two groups combined showed a significant difference in protein concentration (Mann-Whitney U test, p = 0.03)