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

English version

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: https://doi.org/10.1371/journal.pgen.1008926

Souhrn

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

Zdroje

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