Genomic Assessment of Cancer Susceptibility in the Threatened Catalina Island Fox (Urocyon littoralis catalinae).

ABSTRACT

Small effective population sizes raise the probability of extinction by increasing the frequency of potentially deleterious alleles and reducing fitness. However, the extent to which cancers play a role in the fitness reduction of genetically depauperate wildlife populations is unknown. Santa Catalina island foxes (Urocyon littoralis catalinae) sampled in 2007-2008 have a high prevalence of ceruminous gland tumors, which was not detected in the population prior to a recent bottleneck caused by a canine distemper epidemic. The disease appears to be associated with inflammation from chronic ear mite (Otodectes) infections and secondary elevated levels of Staphyloccus pseudointermedius bacterial infections. However, no other environmental factors to date have been found to be associated with elevated cancer risk in this population. Here, we used whole genome sequencing of the case and control individuals from two islands to identify candidate loci associated with cancer based on genetic divergence, nucleotide diversity, allele frequency spectrum, and runs of homozygosity. We identified several candidate loci based on genomic signatures and putative gene functions, suggesting that cancer susceptibility in this population may be polygenic. Due to the efforts of a recovery program and weak fitness effects of late-onset disease, the population size has increased, which may allow selection to be more effective in removing these presumably slightly deleterious alleles. Long-term monitoring of the disease alleles, as well as overall genetic diversity, will provide crucial information for the long-term persistence of this threatened population.