Polymorphisms of a scrapie-associated fibril protein (PrP) gene and their association with susceptibility to experimentally induced scrapie in Cheviot sheep in the United States

Alma Maciulis From the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture, Utah State University, Logan, Utah 84322-4815 (Maciulis, Wang, Foote), and the AFRC Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH92JF, Scotland (Hunter, Goldmann, Hope).

Search for other papers by Alma Maciulis in
Current site
Google Scholar
PubMed
Close
 MS
,
Nora Hunter From the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture, Utah State University, Logan, Utah 84322-4815 (Maciulis, Wang, Foote), and the AFRC Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH92JF, Scotland (Hunter, Goldmann, Hope).

Search for other papers by Nora Hunter in
Current site
Google Scholar
PubMed
Close
 PhD
,
Shiquan Wang From the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture, Utah State University, Logan, Utah 84322-4815 (Maciulis, Wang, Foote), and the AFRC Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH92JF, Scotland (Hunter, Goldmann, Hope).

Search for other papers by Shiquan Wang in
Current site
Google Scholar
PubMed
Close
 PhD
,
Wilfred Goldmann From the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture, Utah State University, Logan, Utah 84322-4815 (Maciulis, Wang, Foote), and the AFRC Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH92JF, Scotland (Hunter, Goldmann, Hope).

Search for other papers by Wilfred Goldmann in
Current site
Google Scholar
PubMed
Close
 PhD
,
James Hope From the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture, Utah State University, Logan, Utah 84322-4815 (Maciulis, Wang, Foote), and the AFRC Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH92JF, Scotland (Hunter, Goldmann, Hope).

Search for other papers by James Hope in
Current site
Google Scholar
PubMed
Close
 PhD
, and
Warren C. Foote From the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture, Utah State University, Logan, Utah 84322-4815 (Maciulis, Wang, Foote), and the AFRC Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH92JF, Scotland (Hunter, Goldmann, Hope).

Search for other papers by Warren C. Foote in
Current site
Google Scholar
PubMed
Close
 PhD

Click on author name to view affiliation information

SUMMARY

The duration of the incubation period for scrapie, a fatal transmissible neurodegenerative disorder of sheep and goats, is mainly determined by the Sip gene, which has 2 alleles (sA—susceptible and pA—resistant). A diagnostic test is not available to detect scrapie in live animals. We analyzed genomic dna extracted from frozen sheep brains collected from Cheviot sheep of the United States that had been inoculated with the SSBP/1 scrapie inoculum. Digestion of the dna with EcoRI or HindIII followed by the addition of a scrapie-associated fibril protein (PrP)-specific marker probe, yielded fragments of 6.8 (e1) and 4.0 (e3) kb, or 5.0 (h1) and 3.4 (h2) kb, respectively. Fragments e1 and h2 were associated with the histopathologic diagnosis of scrapie, and fragments e3 and h1 were associated with survival. A valine/alanine polymorphism within the PrP coding region that resulted in a BspHI site was further used to determine the genotype of these Cheviot sheep. Digestion of polymerase chain reaction fragments with BspHI resulted in an undigested fragment b– (0.840 kb), digested fragments b+ (0.460 and 0.380 kb), or both types of fragments. Survival time of b+/b+ homozygous sheep was significantly (P < 0.01) shorter (218 ± 26.0 days) than survival time for b−/b− sheep (> 700 days after inoculation). Results indicated that b+ and b− are markers for the Sip sA and pA alleles, respectively. The intermediate duration of the incubation period for heterozygous sheep (b+/b−; 342.9 ± 25.3 days) indicated that the Sip sA allele is expressed codominantly to the Sip pA allele.

SUMMARY

The duration of the incubation period for scrapie, a fatal transmissible neurodegenerative disorder of sheep and goats, is mainly determined by the Sip gene, which has 2 alleles (sA—susceptible and pA—resistant). A diagnostic test is not available to detect scrapie in live animals. We analyzed genomic dna extracted from frozen sheep brains collected from Cheviot sheep of the United States that had been inoculated with the SSBP/1 scrapie inoculum. Digestion of the dna with EcoRI or HindIII followed by the addition of a scrapie-associated fibril protein (PrP)-specific marker probe, yielded fragments of 6.8 (e1) and 4.0 (e3) kb, or 5.0 (h1) and 3.4 (h2) kb, respectively. Fragments e1 and h2 were associated with the histopathologic diagnosis of scrapie, and fragments e3 and h1 were associated with survival. A valine/alanine polymorphism within the PrP coding region that resulted in a BspHI site was further used to determine the genotype of these Cheviot sheep. Digestion of polymerase chain reaction fragments with BspHI resulted in an undigested fragment b– (0.840 kb), digested fragments b+ (0.460 and 0.380 kb), or both types of fragments. Survival time of b+/b+ homozygous sheep was significantly (P < 0.01) shorter (218 ± 26.0 days) than survival time for b−/b− sheep (> 700 days after inoculation). Results indicated that b+ and b− are markers for the Sip sA and pA alleles, respectively. The intermediate duration of the incubation period for heterozygous sheep (b+/b−; 342.9 ± 25.3 days) indicated that the Sip sA allele is expressed codominantly to the Sip pA allele.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 67 67 13
PDF Downloads 9 9 0
Advertisement