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Localization of a feline autosomal dominant dwarfism locus: a novel model of chondrodysplasia

L.A. Lyons, D.B. Fox, K.L. Chesney, L.G. Britt, R.M. Buckley, J.R. Coates, B. Gandolfi, R.A. Grahn, M.J. Hamilton, J.R. Middleton, S.T. Sellers, N.A. Villani, S. Pfleuger, the 99 Lives Consortium
doi: https://doi.org/10.1101/687210
L.A. Lyons
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, CA, USA
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  • For correspondence: lyonsla@missouri.edu
D.B. Fox
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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K.L. Chesney
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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L.G. Britt
All Creatures Teleradiology, LLC
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R.M. Buckley
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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J.R. Coates
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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B. Gandolfi
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, CA, USA
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R.A. Grahn
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, CA, USAVeterinary Genetics Laboratory, University of California – Davis, Davis, CA, USA
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M.J. Hamilton
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, CA, USADepartment of Cell Biology and Neuroscience, Institute for Integrative Genome Biology, Center for Disease Vector Research, University of California - Riverside, Riverside, CA, USA
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J.R. Middleton
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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S.T. Sellers
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
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N.A. Villani
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, CA, USA
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S. Pfleuger
Veterinary Medical Diagnostic Laboratory College of Veterinary Medicine University of Missouri Columbia, MO, USA
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Abstract

Despite the contribution of a few major genes for disproportionate dwarfism in humans, many dwarf patients are yet genetically undiagnosed. In domestic cats, disproportionate dwarfism has led to the development of a defined breed, the Munchkin or Minuet. This study examined the genetic aspects of feline dwarfism to consider cats as a new biomedical model. DNA from dwarf cats was genetically analyzed using parentage, linkage, and genome-wide association studies as well as whole genome sequencing. Each genetic approach localized the dwarfism phenotype to a region on cat chromosome B1. No coding variants suspected as causal for the feline dwarfism were identified but a critical region of ∼5.7 Mb from B1:170,278,183-175,975,857 was defined, which implicates a novel gene controlling disproportionate dwarfism. A yet unidentified but novel gene variant, likely structural or regulatory, produces disproportionate dwarfism in cats, which may define undiagnosed human patients.

Footnotes

  • In memoriam, Leslie A. Lyons – lyonsla{at}missouri.edu, Derek B. Fox - foxdb{at}missouri.edu, Kari L. Chesney - chesneyk{at}mizzou.edu, Lisa G. Britt - lgb1991heart{at}gmail.com, Reuben M. Buckley – bucklyrm{at}missouri.edu, Joan R. Coates - coatesj{at}missouri.edu, Barbara Gandolfi – Barbara.Gandolfi{at}Idexx.com, Robert A. Grahn – ragrahn{at}ucdavis.edu, Michael J. Hamilton - mhami004{at}ucr.edu, John R. Middleton - middletonjr{at}missouri.edu, Samantha T. Sellers - ststgb{at}mail.missouri.edu, Natalie A. Villani - villanin{at}missouri.edu, Solveig Pfleuger – not available

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 08, 2019.
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Localization of a feline autosomal dominant dwarfism locus: a novel model of chondrodysplasia
L.A. Lyons, D.B. Fox, K.L. Chesney, L.G. Britt, R.M. Buckley, J.R. Coates, B. Gandolfi, R.A. Grahn, M.J. Hamilton, J.R. Middleton, S.T. Sellers, N.A. Villani, S. Pfleuger, the 99 Lives Consortium
bioRxiv 687210; doi: https://doi.org/10.1101/687210
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Localization of a feline autosomal dominant dwarfism locus: a novel model of chondrodysplasia
L.A. Lyons, D.B. Fox, K.L. Chesney, L.G. Britt, R.M. Buckley, J.R. Coates, B. Gandolfi, R.A. Grahn, M.J. Hamilton, J.R. Middleton, S.T. Sellers, N.A. Villani, S. Pfleuger, the 99 Lives Consortium
bioRxiv 687210; doi: https://doi.org/10.1101/687210

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