A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism

PLoS Genet. 2020 Oct 22;16(10):e1008926. doi: 10.1371/journal.pgen.1008926. eCollection 2020 Oct.


The domestic cat (Felis catus) numbers over 94 million in the USA alone, occupies households as a companion animal, and, like humans, suffers from cancer and common and rare diseases. However, genome-wide sequence variant information is limited for this species. To empower trait analyses, a new cat genome reference assembly was developed from PacBio long sequence reads that significantly improve sequence representation and assembly contiguity. The whole genome sequences of 54 domestic cats were aligned to the reference to identify single nucleotide variants (SNVs) and structural variants (SVs). Across all cats, 16 SNVs predicted to have deleterious impacts and in a singleton state were identified as high priority candidates for causative mutations. One candidate was a stop gain in the tumor suppressor FBXW7. The SNV is found in cats segregating for feline mediastinal lymphoma and is a candidate for inherited cancer susceptibility. SV analysis revealed a complex deletion coupled with a nearby potential duplication event that was shared privately across three unrelated cats with dwarfism and is found within a known dwarfism associated region on cat chromosome B1. This SV interrupted UDP-glucose 6-dehydrogenase (UGDH), a gene involved in the biosynthesis of glycosaminoglycans. Importantly, UGDH has not yet been associated with human dwarfism and should be screened in undiagnosed patients. The new high-quality cat genome reference and the compilation of sequence variation demonstrate the importance of these resources when searching for disease causative alleles in the domestic cat and for identification of feline biomedical models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cats
  • Chromosome Mapping
  • Dwarfism / genetics*
  • F-Box-WD Repeat-Containing Protein 7 / genetics*
  • Genetic Predisposition to Disease
  • Genome / genetics*
  • Genomics
  • Humans
  • Male
  • Molecular Sequence Annotation
  • Phylogeny
  • Polymorphism, Single Nucleotide / genetics
  • Uridine Diphosphate Glucose Dehydrogenase / genetics*
  • Whole Genome Sequencing*


  • F-Box-WD Repeat-Containing Protein 7
  • UGDH protein, human
  • Uridine Diphosphate Glucose Dehydrogenase

Grants and funding

Funding for this project has been provided in part by Nestlé Purina to pay for personnel salaries and sequencing (W.C.W. and R.M.), Wisdom Health unit of Mars Veterinary to pay for personnel salaries (L.A.L.), Zoetis to pay for RNA sequencing used in annotation (L.A.L), the University of Missouri College of Veterinary Medicine Gilbreath-McLorn endowment was used for the BioNano optical map (L.A.L.), and Winn Feline Foundation W15-008 (W.J.M.), Winn Feline Foundation/Miller Trust MT14-009 (W.J.M.) (https://www.winnfelinefoundation.org/), and Morris Animal Foundation D16FE-011 (W.J.M.) (https://www.morrisanimalfoundation.org/) were all used for PacBio sequencing. The funders had no role in study design, data collection, data analysis, interpretation of results, or decision to publish.