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United States Department of Agriculture

Agricultural Research Service

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Location: Virus and Prion Research

Title: Genetic variation of the prion protein gene (PRNP) in alpaca (Vicugna pacos))

Author
item Vermette, Melissa
item Schleining, J
item Greenlee, Justin
item Smith, Jodi

Submitted to: Gene Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/7/2016
Publication Date: 6/8/2016
Citation: Vermette, M.S., Schleining, J.A., Greenlee, J.J., Smith, J.D. 2016. Genetic variation of the prion protein gene (PRNP) in alpaca (Vicugna pacos). Gene Reports. 4:213–217.

Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. Alpacas are used for fiber production in North America and could come into contact with species infected with a prion disease or be housed in a prion contaminated environment. There are no reports of prion disease in alpacas suggesting the possibility that alpacas may be resistant to prion diseases present in North American livestock and wildlife. Susceptibility in other species has been shown to be affected by amino acids in certain locations of the prion protein (PRNP). The purpose of this study was to determine the PRNP amino acid sequence in alpacas and compare to known sequence of other domesticated animals. In the course of this work, the alpaca sequence was shown to be highly similar to that of camels, sheep, cattle, and deer. Variances (polymorphisms) in the prion amino acid sequence unique to alpacas were identified at 10 locations including two amino acid deletions and one insertion. This information could be used by other researchers to perform structural modeling of the prion protein to determine how the PRNP may affect the potential susceptibility of alpacas to prion diseases.

Technical Abstract: Transmissible spongiform encephalopathies (TSE) are caused by accumulation of a misfolded form of the prion protein (PrP). The normal cellular isoform of PrP is produced by the prion gene (PRNP) and is highly expressed in the central nervous system. Currently, there is an absence of information regarding the genetic sequence of alpaca PRNP and the potential susceptibility of this species to TSE. The objective of this study was to sequence the open reading frame of the alpaca prion gene and analyze this sequence for variation within the alpaca population and for homology to TSE-susceptible species. We sequenced the open reading frame of the prion gene of 40 alpacas of Huacaya or Suri descent. Length polymorphisms were identified within the sampled population. A subset (15%) of animals contained an additional 24 base pairs within the putative octapeptide repeat region. This polymorphism was independent of breed and sex. The majority (52.5%) of animals were heterozygous, expressing both longer and shorter alleles. Comparison with proven TSE-susceptible species (sheep, cattle, deer) revealed polymorphisms at codons I6M, A16V, M17T, G92–, –95G, N111S, R167K, N/T177S, I206V, S225Y, Y228S, Q230G, and L237–. Sequence alignment showed high homology compared to camel (>95%), sheep (>88%), cattle (>87%) and deer (>88%) PRNP sequence. This study demonstrates intraspecies variability within the PRNP open reading frame in alpacas and overall high sequence homology to TSE-susceptible species, providing foundational data for further research on the potential susceptibility of alpacas to TSE.

Last Modified: 8/24/2016
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