COSEGREGATION OF PORCINE MALIGNANT HYPERTHERMIA AND A PROBABLE CAUSAL MUTATION IN THE SKELETAL-MUSCLE RYANODINE RECEPTOR GENE IN BACKCROSS FAMILIES

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 Omax = 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. © 1991.