Journal article
A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle
Proceedings of the National Academy of Sciences - PNAS, Vol.106(46), pp.19250-19255
11/17/2009
Handle:
https://hdl.handle.net/2376/109357
PMCID: PMC2780805
PMID: 19887637
Abstract
Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers
AFR227
and
BM4311
. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (
PRKG2
). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (
COL2
). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate
COL2
expression in cell culture. Real-time PCR results confirmed that
COL2
is overexpressed in cells that overexpressed
R678X PRKG2
as compared with WT
PRKG2
. Furthermore,
COL2
and
COL10
mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the
R678X
mutation is functional, resulting in a loss of PRKG2 regulation of
COL2
and
COL10
mRNA expression. Therefore, we present
PRKG2 R678X
as a causative mutation for dwarfism cattle.
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Details
- Title
- A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle
- Creators
- James E Koltes - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150Bishnu P Mishra - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150Dinesh Kumar - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150Ranjit S Kataria - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150Liviu R Totir - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150Rohan L Fernando - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150Rowland Cobbold - Department of Veterinary Public Health, University of Queensland, St. Lucia, QLD 4072, AustraliaDavid Steffen - Department of Veterinary and Biomedical Sciences, University of Nebraska, P.O. Box 830905, Lincoln, NE 68583-0905; andWouter Coppieters - Unit of Animal Genomics, GIGA-Research and Faculty of Veterinary Medicine, University of Liege (B34), 1 Av de l'Hopital, 4000 Liege, BelgiumMichel Georges - Unit of Animal Genomics, GIGA-Research and Faculty of Veterinary Medicine, University of Liege (B34), 1 Av de l'Hopital, 4000 Liege, BelgiumJames M Reecy - Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011-3150
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.106(46), pp.19250-19255
- Publisher
- National Academy of Sciences
- Identifiers
- 99900547295101842
- Language
- English
- Resource Type
- Journal article