Measures of Homozygosity and Relationship to Genetic Diversity in the Bearded Collie Breed

<b>Background:</b> Genetic diversity in closed populations, such as pedigree dogs, is of concern for maintaining the health and vitality of the population in the face of evolving challenges. Measures of genetic diversity rely upon estimates of homozygosity without consideration of whether the homozygosity is desirable or undesirable or if heterozygosity has a functional impact. Pedigree coefficients of inbreeding have been the classical approach yet they are inadequate unless based upon the entire population. <b>Methods:</b> Homozygosity measures based upon pedigree analyses (<i>n</i> = 11,898), SNP array data (<i>n</i> = 244), and whole genome sequencing (<i>n</i> = 23) were compared in the Bearded Collie, as well as a comparison of SNP array data to a pedigree cohort (<i>n</i> = 5042) and a mixed-breed cohort (<i>n</i> = 1171). <b>Results:</b> Molecular measures based upon DNA are more informative on an individual's homozygosity levels than pedigree analyses, although SNP coefficients of inbreeding overestimate the level of inbreeding based on the nature of SNP array methodology. Whole genome sequence (WGS) analyses revealed that the heterozygosity observed is generally in variants having neutral or low impact, which would indicate that the variability may not contribute substantially to functional diversity in the population. The majority of high-impact variants were observed in the shortest runs of homozygosity (ROH) reflecting ancestral breeding and domestication practices. As expected, mixed-breed dogs displayed higher measures of genomic diversity than either Bearded Collies or other pedigree dogs as a whole using the current paradigm algorithm models to calculate homozygosity. <b>Conclusions:</b> Using typical DNA-based measures reflect only a single individual and not the population thereby failing to account for regions of homozygosity that reflect ancestral breeding, domestication history, breed-defining regions, or regions positively selected for health traits. Incorporating measures of genetic diversity into dog breeding schemes is meritorious. However, until measures of diversity can distinguish between breed-defining homozygosity and homozygosity associated with positive health alleles, the measures to use as selection tools need refinement before their widespread implementation.