Advances in Felid Genetics and Genomics

Abstract

The cat family (Felidae) has a unique evolutionary history. Their highly conserved genomic architecture offers us a glimpse into the processes of domestication and adaptive evolution. The ongoing development of genomic tools in felids has largely focused on the domestic cat (Felis catus) and its biomedical relevance to humans. Generations of inbreeding for aesthetic traits in domestic cat breeds has resulted in populations with a simplified genetic landscape, suitable for genome-wide surveys that explore breed-specific traits. While recent advances have increased opportunities for conservation genomics research, species of conservation value typically lack basic genomic resources necessary to perform efficient, cost-effective and pragmatic genome-scale research. In the absence of high-quality reference genomes, cross-species alignment and variant calling methods can serve as a reliable, cost-effective method for variant discovery, thanks to the high degree of genomic synteny among felids. In this thesis, genomic tools developed for the domestic cat are applied to demographic and health scenarios in domestic and wild felids. I demonstrate the advantages of using pedigreed breeds to construct the genetic landscape of complex disease in humans using the Burmese breed as a naturally occurring model of type 2 diabetes. I demonstrate the cross-species utility of genomic resources in wild felid conservation using commonly applied reference-based methods. I use the feline reference genome to perform variant detection across Sumatran tigers (Panthera tigris sumatrae), snow leopards (Panthera uncia) and cheetahs (Acinonyx jubatus), to gain insights into population dynamics, evolutionary history and disease management. Further, I compare two commonly used low-density variant datasets: reduced representation sequencing and feline genotyping array, in their ability to estimate population structure and identify genomic regions underlying selection in these wild species.