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

Autoři: Reuben M. Buckley aff001;  Brian W. Davis aff002;  Wesley A. Brashear aff002;  Fabiana H. G. Farias aff003;  Kei Kuroki aff005;  Tina Graves aff006;  LaDeana W. Hillier aff006;  Milinn Kremitzki aff006;  Gang Li aff002;  Rondo P. Middleton aff007;  Patrick Minx aff008;  Chad Tomlinson aff006;  Leslie A. Lyons aff001;  William J. Murphy aff002;  Wesley C. Warren aff009
Působiště autorů: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States of America aff001;  Department of Veterinary Integrative Biosciences, Interdisciplinary Program in Genetics, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America aff002;  Department of Psychiatry, Washington University, St. Louis, Missouri, United States of America aff003;  NeuroGenomics and Informatics, Washington University, St. Louis, Missouri, United States of America aff004;  Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States of America aff005;  McDonnell Genome Institute, Washington University School of Medicine, St Louis, Missouri, United States of America aff006;  Nestlé Purina Research, Saint Louis, Missouri, United States of America aff007;  Donald Danforth Plant Science, St Louis, Missouri, United States of America aff008;  Division of Animal Sciences, School of Medicine, University of Missouri, Columbia, Missouri, United States of America aff009
Vyšlo v časopise: A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1008926
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008926


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.

Klíčová slova:

Alleles – Cats – Domestic animals – Genome annotation – Mammalian genomics – Pets and companion animals – Sequence alignment – Dwarfism


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