Abstract
BackgroundLeonberger is a giant dog breed formed in the 1850s in Germany. Its post-World War II popularity has resulted in a current global population of ~ 30,000 dogs. The breed has predispositions to neurodegenerative disorders and cancer, which is likely due in large part to limited genetic diversity. However, to date there is no scientific literature on the overall demography and genomic architecture of this breed.ResultsWe assessed extensive pedigree records, SNP array genotype data, and whole-genome sequences (WGS) on 142,072, 1203 and 39 Leonberger dogs, respectively. Pedigree analyses identified 22 founder animals and revealed an apparent popular sire effect. The average pedigree-based inbreeding coefficient of 0.29 and average kinship of 0.31 show a dramatic loss of genetic diversity. The observed average life span decreased over time from 9.4 years in 1989 to 7.7 years in 2004. A global health survey confirmed a high prevalence of cancer and neurological disorders. Analysis of SNP-based runs of homozygosity (ROH) identified 125,653 ROH with an average length of 5.88 Mb, and confirmed an average inbreeding coefficient of 0.28. Genome-wide filtering of the WGS data revealed 28 non-protein-changing variants that were present in all Leonberger individuals and a list of 22 potentially pathogenic variants for neurological disorders of which 50% occurred only in Leonbergers and 50% occurred rarely in other breeds. Furthermore, one of the two mtDNA haplogroups detected was present in one dog only.ConclusionsThe increasing size of the Leonberger population has been accompanied by a considerable loss of genetic diversity after the bottleneck that occurred in the 1940s due to the intensive use of popular sires resulting in high levels of inbreeding. This might explain the high prevalence of certain disorders; however, genomic data provide no evidence for fixed coding variants that explain these predispositions. The list of candidate causative variants for polyneuropathy needs to be further evaluated. Preserving the current genetic diversity is possible by increasing the number of individuals for breeding while restricting the number of litters per sire/dam. In addition, outcrossing would help optimize long-term genetic diversity and contribute to the sustainability and health of the population.
Highlights
Leonberger is a giant dog breed formed in the 1850s in Germany
Polymorphic microsatellite marker genotype data have been used to evaluate the genetic diversity in dogs (e.g. [7, 8]), and more recently, genomewide single nucleotide polymorphism (SNP) genotype data have been used in several breeds [9,10,11,12,13]
A popular sire was defined as a male dog that sired at least 33 puppies, corresponding to five litters based on the observed average litter size
Summary
Its post-World War II popularity has resulted in a current global population of ~ 30,000 dogs. The breed became more popular after World War II, resulting in an estimated current population. Polymorphic microsatellite marker genotype data have been used to evaluate the genetic diversity in dogs Studies are based on SNP genotyping data of variable marker density and generally for less than 100 selected individuals per breed; e.g. Boccardo et al [12] analysed only 34 individuals of the German shorthaired pointer breed to estimate a genomic inbreeding coefficient F_ROH of 0.17, whereas a mean inbreeding coefficient of only 0.023 was found based on genealogical information, showing the latter was incomplete
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