Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families

Abstract

A study of the inheritance of malignant hyperthermia (MH) in the British Landrace breed revealed the same substitution of T for C at nucleotide 1843 in the ryanodine receptor ( RYR1) gene that was previously shown to be correlated with MH in five Canadian swine breeds. Cosegregation of the mutation with MH in 338 informative meioses led to a lod score of 101.75 for linkage at O max = 0.0. The substitution was also associated with a HinPI − BanII + RasI − haplotype in this breed, as in the five breeds tested earlier, suggesting its orgin in a common founder animal. DNA-based detection of the MH status in 376 MH-susceptible heterozygous ( N n ) and homozygous ( n n ) pigs was shown to be accurate, eliminating the 5% diagnostic error that is associated with the halothane challenge test and flanking marker haplotyping procedures in current diagnostic use. These results strongly support the view that the substitution of T for C at nucleotide 1843 is the causative mutation in porcine MH and demonstrate the feasibility of rapid, accurate, noninvasive, large-scale testing for porcine MH status using DNA-based tests for the mutation.