Originally published as Genetics Published Articles Ahead of Print on July 1, 2007.

Genetics, Vol. 176, 2601-2610, August 2007, Copyright © 2007
doi:10.1534/genetics.107.074328

Epistasis Between Calpain 1 and Its Inhibitor Calpastatin Within Breeds of Cattle

W. Barendse^*,1, B. E. Harrison^*, R. J. Hawken^*, D. M. Ferguson^,2, J. M. Thompson, M. B. Thomas^* and R. J. Bunch^*

^* Commonwealth Scientific and Industrial Research Organization Livestock Industries and Cooperative Research Centre for Cattle and Beef Quality and Beef Genetic Technologies, Queensland Bioscience Precinct, St. Lucia 4067, Queensland, Australia, Food Science Australia, Cannon Hill 4170, Queensland, Australia and Department of Animal Science, University of New England, Armidale 2351, New South Wales, Australia

¹ Corresponding author: CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Rd., St. Lucia 4067, Queensland, Australia.
E-mail: Bill.Barendse{at}csiro.au

The calpain gene family and its inhibitors have diverse effects, many related to protein turnover, which appear to affect a range of phenotypes such as diabetes, exercise-induced muscle injury, and pathological events associated with degenerative neural diseases in humans, fertility, longevity, and postmortem effects on meat tenderness in livestock species. The calpains are inhibited by calpastatin, which binds directly to calpain. Here we report the direct measurement of epistatic interactions of causative mutations for quantitative trait loci (QTL) at calpain 1 (CAPN1), located on chromosome 29, with causative mutations for QTL variation at calpastatin (CAST), located on chromosome 7, in cattle. First we identified potential causative mutations at CAST and then genotyped these along with putative causative mutations at CAPN1 in >1500 cattle of seven breeds. The maximum allele substitution effect on the phenotype of the CAPN1:c.947G>C single nucleotide polymorphism (SNP) was 0.14 _p (P = 0.0003) and of the CAST:c.155C>T SNP was also 0.14 _p (P = 0.0011) when measured across breeds. We found significant epistasis between SNPs at CAPN1 and CAST in both taurine and zebu derived breeds. There were more additive x dominance components of epistasis than additive x additive and dominance x dominance components combined. A minority of breed comparisons did not show epistasis, suggesting that genetic variation at other genes may influence the degree of epistasis found in this system.

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