PRION GENE SEQUENCE VARIATION WITHIN DIVERSE GROUPS OF U.S. SHEEP, BEEF CATTLE, AND DEER

Authors: Heaton, Michael - Mike; Leymaster, Kreg; Freking, Bradley - Brad; HAWK, DEEDRA - WYOMING GAME & FISH DEPT; Smith, Timothy - Tim; Keele, John; Snelling, Warren; Fox, James; Chitko-Mckown, Carol; Laegreid, William

Submitted to: Mammalian Genome
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2003
Publication Date: 11/1/2003
Citation: HEATON, M.P., LEYMASTER, K.A., FREKING, B.A., HAWK, D.A., SMITH, T.P., KEELE, J.W., SNELLING, W.M., FOX, J.M., CHITKO MCKOWN, C.G., LAEGREID, W.W. PRION GENE SEQUENCE VARIATION WITHIN DIVERSE GROUPS OF U.S. SHEEP, BEEF CATTLE, AND DEER. MAMMALIAN GENOME. 2003. V. 14. P. 765-777.

Interpretive Summary: Transmissible spongiform encephalopathies (TSEs) are diseases of humans and animals characterized by long incubation periods, slow onset of neurologic dysfunction, and inevitable death. The most notable TSEs include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in deer. Cattle with BSE have been implicated in one human TSE, variant CJD, through the consumption of beef from affected animals. The development of TSEs is thought to be caused by abnormal forms of prions. Prions are naturally-occurring mammalian proteins. Genetic variation in prion genes has been correlated with susceptibility to TSEs in humans and sheep, however, similar correlations in cattle and deer are unknown. The present report provides a systematic and detailed description of prion variation in U.S. sheep, cattle, and deer. The majority of this variation was previously unknown. The report also provides estimates for the most resistant and susceptible genotypes in sheep breeds that contribute significantly to U.S. production. Furthermore, this description of prion gene variation in U.S. populations facilitates the design of accurate genetic tests for identifying animals resistant to TSEs. Direct selection for the resistant allele would significantly reduce the overall genetic risk of developing scrapie is compliant with scrapie eradication programs.

Technical Abstract: Prions are proteins that play a central role in transmissible spongiform encephalopathies in a variety of mammals. Among the most notable disorders in ungulates are scrapie in sheep, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer. Single nucleotide polymorphisms in the sheep prion gene (PRNP) have been correlated with susceptibility to natural scrapie in some populations. Similar correlations have not been reported in cattle or deer; however, characterization of PRNP nucleotide diversity in those species is incomplete. This report describes nucleotide sequence variation and frequency estimates for the PRNP locus in diverse groups of U.S. sheep, U.S. beef cattle, and free-ranging deer (O. virginianus and O. hemionus from Wyoming). DNA segments corresponding to the complete prion coding sequence and a 596-bp portion of the PRNP promoter region were amplified and sequenced from DNA panels with 90 sheep, 96 cattle, and 94 deer. Each panel was designed to contain the most diverse germplasm available from their respective populations to facilitate polymorphism detection. Sequence comparisons identified a total of 86 polymorphisms. Previously unreported polymorphisms were identified in sheep (nine), cattle (13), and deer (32). The number of individuals sampled within each population was sufficient to detect more than 95% of all alleles present at a frequency greater than 0.02. The estimation of PRNP allele and genotype frequencies in these populations provides a detailed description of their genetic structure, a goal in understanding the population genetics of prion diseases. Furthermore, it facilitates the design of accurate genotype assays for use in genetic epidemiology and disease control.