Abstract
BackgroundA higher prevalence of inherited disorders among companion animals are often rooted in their historical restricted artificial selection for a variety of observed phenotypes that eventually decreased genetic diversity. Cats have been afflicted with many inherited diseases due to domestication and intense breed selection. Advances in sequencing technology have generated a more comprehensive way to access genetic information from an individual, allowing identification of putative disease-causing variants and in practice a means to avoid their spread and thus better pedigree management. We examine variants in three domestic shorthair cats and then calculated overall genetic diversity to extrapolate the benefits of this data for breeding programs within a feline colony.ResultsWe generated whole genome sequence (WGS) data for three related cats that belong to a large feline pedigree colony. Genome-wide coverage ranged from 27-32X, from which we identified 18 million variants in total. Previously known disease-causing variants were screened in our cats, but none carry any of these known disease alleles. Loss of function (LoF) variants, that are in genes associated with a detrimental phenotype in human or mice were chosen for further evaluation on the comparative impact inferred. A set of LoF variants were observed in four genes, each with predicted detrimental phenotypes as a result. However, none of our cats displayed the expected disease phenotypes. Inbreeding coefficients and runs of homozygosity were also evaluated as a measure of genetic diversity. We find low inbreeding coefficients and total runs of homozygosity, thus suggesting pedigree management of genetic relatedness is acceptable.ConclusionsThe use of WGS of a small sampling among a large feline colony has enabled us to identify possible disease-causing variants, their genotype state and measure pedigree management of genetic diversity. We contend a limited but strategic sampling of feline colony individuals using WGS can inform veterinarians of future health anomalies and guide breeding practices to ensure healthy genetic diversity.
Highlights
A higher prevalence of inherited disorders among companion animals are often rooted in their historical restricted artificial selection for a variety of observed phenotypes that eventually decreased genetic diversity
Lyons et al [3] have identified the causative mutation for Polycystic kidney disease (PKD) in the gene PKD1, and a commercial genetic test is available enabling Persian cat breeders to make mating decisions based on genetic information
Examination of the regions containing the Single nucleotide variant (SNV) revealed that two of those regions were located within sequences homologous to other sequences in the cat genome, which may suggest that misalignment created the false positives
Summary
A higher prevalence of inherited disorders among companion animals are often rooted in their historical restricted artificial selection for a variety of observed phenotypes that eventually decreased genetic diversity. The use of pedigreed colonies remains a powerful resource to study many phenotypes of interest in great detail, yet among companion animals, dogs and cats, large well-maintained pedigrees for such use are rare and not readily available Given this rarity, their optimal use in the understanding of health and behavioral. Farias et al BMC Veterinary Research (2017) 13:225 ability to return to banked samples for basic disease research or clinical testing to provide optimal care has veterinarians excited about these health management opportunities Data collection such as a whole genome or targeted sequencing, immunoassays, metabolite profiling, fixed genotyping and others, collectively or in isolation can drive discovery of the sources of trait diversity linked to genetic variation. Lyons et al [3] have identified the causative mutation for PKD in the gene PKD1, and a commercial genetic test is available enabling Persian cat breeders to make mating decisions based on genetic information
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