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The Genetic Approach to Controlling BSE
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<blockquote data-quote="flounder" data-source="post: 272028" data-attributes="member: 3519"><p>The Genetic Approach to Controlling BSE </p><p></p><p>By: David A. Rodger </p><p></p><p></p><p></p><p>Stephen Moore was on holiday in his native </p><p></p><p>Australia back in May 2003, when he received </p><p></p><p>the telephone call that changed his life. "A Canadian </p><p></p><p>reporter was on the line asking me to </p><p></p><p>comment on a case of bovine spongiform encephalopathy </p><p></p><p>(BSE) in Alberta," says Dr. </p><p></p><p>Moore "I still don't know how he tracked me </p><p></p><p>down. There wasn't much I could say because, </p><p></p><p>of course, this was news to me." </p><p></p><p>Back in Edmonton, where he is Chair of Bovine </p><p></p><p>Genomics in the University of Alberta's </p><p></p><p>Department of Agricultural, Food and Nutritional </p><p></p><p>Science, Dr. Moore was quickly brought </p><p></p><p>up to date. He and his research group had </p><p></p><p>been intimately involved in mapping the bovine </p><p></p><p>genome and were considered leaders in identifying </p><p></p><p>and characterizing genes that affect cattle </p><p></p><p>growth, yield, fat content and meat tenderness. </p><p></p><p>"There's a genetic component in BSE susceptibility," </p><p></p><p>he explains. "You only have to look at </p><p></p><p>the UK where some animals in a herd came </p><p></p><p>down with the disease while others didn't. </p><p></p><p>This was despite their having eaten the same </p><p></p><p>contaminated feed. What are the genetic factors </p><p></p><p>that render cattle more susceptible or </p><p></p><p>more resistant to BSE? The answers will help </p><p></p><p>us with intervention, diagnosis, and treatment." </p><p></p><p>In January 2006, the Alberta Prion Research </p><p></p><p>Institute appointed Dr. Moore its first scientific </p><p></p><p>director. Dr. Moore also leads PrioNet's Research </p><p></p><p>Theme I on BSE. He is Principal Investigator </p><p></p><p>on two APRI-PrioNet co-funded projects ...2 </p><p></p><p></p><p></p><p>BSE </p><p></p><p>- one related to BSE and the other to Chronic Wasting </p><p></p><p>Disease. Other partners include the University of Alberta, </p><p></p><p>National Microbiology Laboratories - Public </p><p></p><p>Health Agency of Canada, National Centre for Foreign </p><p></p><p>Animal Disease - Canadian Food Inspection Agency. </p><p></p><p>"The only place in the world that has had a statistically </p><p></p><p>significant number of BSE cases is the UK," he says. </p><p></p><p>"The number in Canada is, thankfully, too few for genetic </p><p></p><p>analysis. So, two of my students went to the </p><p></p><p>Rosslyn Institute in Scotland to extract DNA from the </p><p></p><p>blood samples gathered from BSE-infected cattle. That </p><p></p><p>trip was necessary because blood samples are infectious </p><p></p><p>and can't be brought into Canada, while DNA </p><p></p><p>samples are harmless and can be imported. We're now </p><p></p><p>analyzing the DNA." </p><p></p><p>In late July 2006, another case of BSE was discovered, </p><p></p><p>involving a 50-month old Alberta dairy cow born long </p><p></p><p>after Canada's ban on the use of cattle parts in cattle </p><p></p><p>feed. How close is a test that detects BSE and other </p><p></p><p>TSEs in live healthy animals? When will we be able to </p><p></p><p>detect them in live animals as opposed to postmortem? </p><p></p><p>"Before there can be a valid test - dozens are in trials </p><p></p><p>now - two issues must be resolved," says Dr. Moore. </p><p></p><p>"First, it must be easy to collect a sample, and second, </p><p></p><p>it can't cost too much. If the test costs more than the </p><p></p><p>animal is worth, it's of little benefit to producers." For </p><p></p><p>more information visit the Alberta Prion Research </p><p></p><p>Institute web site at <a href="http://www.prioninstitute.ca" target="_blank">http://www.prioninstitute.ca</a>. • </p><p></p><p></p><p></p><p>Coming to terms with Chronic Wasting disease </p><p></p><p>By: David A. Rodger </p><p></p><p></p><p></p><p>PrioNet's Scientific Director, Neil Cashman, </p><p></p><p>has referred to chronic wasting disease </p><p></p><p>(CWD) as "the threat in our own backyard." </p><p></p><p>Indeed, it could be the Transmissible </p><p></p><p>Spongiform Encephalopathy with the greatest </p><p></p><p>potential for species devastation. Leading </p><p></p><p>PrioNet's Theme 2 efforts to understand and </p><p></p><p>control CWD is Ted Leighton of the Western </p><p></p><p>College of Veterinary Medicine in Saskatoon. </p><p></p><p>Dr. Leighton is recognized internationally for </p><p></p><p>his research into wildlife diseases. So it will </p><p></p><p>surprise many to discover that he did his </p><p></p><p>undergraduate work at Cornell University not </p><p></p><p>in science but in Theatre Arts. "Theatre Arts </p><p></p><p>had liberal course requirements," he explains, </p><p></p><p>"enabling me to take natural science, social </p><p></p><p>science and humanities in a mix that provided </p><p></p><p>an excellent general education." He received </p><p></p><p>his veterinary degree from the University of </p><p></p><p>Saskatchewan in 1979, completed a Ph.D. in </p><p></p><p>veterinary pathology at Cornell in 1984, and </p><p></p><p>returned to the University of Saskatchewan </p><p></p><p>later that year as professor of veterinary </p><p></p><p>pathology. </p><p></p><p>Currently Dr. Leighton is Executive Director </p><p></p><p>of the Canadian Cooperative Wildlife Health </p><p></p><p>Centre, which is headquartered in Saskatoon. </p><p></p><p>The organization is a partnership among </p><p></p><p>Canada's veterinary colleges and government </p><p></p><p>agencies responsible for wildlife management, </p><p></p><p>agriculture, and public health. The Centre's </p><p></p><p>mandate is one of disease surveillance. It has </p><p></p><p>programs to monitor the occurrence and </p><p></p><p>spread of such diseases as avian influenza, </p><p></p><p>West Nile virus, and CWD (since 1997). </p><p></p><p>CWD on elk farms in Saskatchewan and </p><p></p><p>Alberta has been eradicated through a </p><p></p><p>systematic program of culling infected or </p><p></p><p>exposed animals. Unfortunately, CWD in wild </p><p></p><p>animals, especially white-tailed and mule deer, </p><p></p><p>is much harder to deal with. Two years ago, </p><p></p><p>the Centre brought together international </p><p></p><p>...2 </p><p></p><p>CWD </p><p></p><p>experts in CWD, disease monitoring, deer biology, and other specialties to help determine </p><p></p><p>whether CWD in wild deer in Canada represented a potential crisis. They determined that it </p><p></p><p>does. </p><p></p><p>"They told us Canada had a few years to develop its response to CWD," he recalls, "because </p><p></p><p>this is a slow-moving disease. They recommended that Canada take determined action to </p><p></p><p>control the disease in wild deer, but warned that there were no proven methods of doing this </p><p></p><p>and that scientific research carried out in the affected areas would have to guide any effective </p><p></p><p>response. They emphasized that there would be large social, ecological or economic </p><p></p><p>consequences for Canada if we do not stop the spread of CWD in wild deer." </p><p></p><p>Dr. Leighton praises the foresight that led to PrioNet's creation, and the flexibility the network </p><p></p><p>has been given to deal with a disease that was, until recently, overshadowed by BSE concerns in </p><p></p><p>Canada. "Our priority with respect to CWD is to learn as much as we can about how it is </p><p></p><p>transmitted. Only then can we develop a program to contain and eliminate it." • </p><p></p><p></p><p></p><p>Coming Together </p><p></p><p>PrioNet established its Student and </p><p></p><p>Young Professional Association </p><p></p><p>(SYPA) at its recent Annual General </p><p></p><p>Meeting 2006. Joel Watts and Qasim </p><p></p><p>Khan (University of Toronto) are </p><p></p><p>SYPA's interim leaders. </p><p></p><p>SYPA includes graduate students, </p><p></p><p>post-doctoral fellows, research associates, </p><p></p><p>and research technicians who </p><p></p><p>are involved with PrioNet's network </p><p></p><p>investigators. The purpose of this </p><p></p><p>association is to organize studentfocused </p><p></p><p>events; liaise with PrioNet </p><p></p><p>regarding issues surrounding students </p><p></p><p>and young professionals; and work </p><p></p><p>together to capitalize on the different </p><p></p><p>programs PrioNet has available to </p><p></p><p>strengthen their research and training </p><p></p><p>experience. </p><p></p><p>PrioNet will be implementing a variety </p><p></p><p>of education and training programs to </p><p></p><p>facilitate learning exchange and enrich </p><p></p><p>the experience of students and young </p><p></p><p>professionals within the network. For </p><p></p><p>resources such as job postings and </p><p></p><p>training updates related to students </p><p></p><p>and young professionals, visit the Education </p><p></p><p>and Training link at </p><p></p><p><a href="http://www.prionetcanada.ca" target="_blank">http://www.prionetcanada.ca</a>. • </p><p></p><p></p><p></p><p>PrioNet's Research Projects Related to CWD & BSE </p><p></p><p>PrioNet Canada will address Canadian prion challenges through its five research themes. The </p><p></p><p>theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy </p><p></p><p>and Chronic Wasting Disease are outlined below: </p><p></p><p></p><p></p><p>Research Theme I: Bovine Spongiform Encephalopathy </p><p></p><p>Theme Leader: Dr. Steven Moore, University of Alberta </p><p></p><p>Associate Leader: Dr. Mike Belosevic, University of Alberta </p><p></p><p>Theme Pathologist: Dr. Stefanie Czub, Canadian Food Inspection Agency </p><p></p><p>A Comprehensive and Comparative Approach to Genetics & Pathobiology of Prion </p><p></p><p>Disease </p><p></p><p>Principal Investigator: Dr. Steven Moore, University of Alberta </p><p></p><p>Co-Investigators: </p><p></p><p>Dr. John Williams, Parco Tecnologico Padano, Italy </p><p></p><p>Dr. Michael Coulthart, Public Health Agency of Canada </p><p></p><p>Dr. Denny Crews, Agriculture & Agri-food Canada </p><p></p><p>Dr. Stefanie Czub, Canadian Food Inspection Agency </p><p></p><p>Dr. Michael Heaton, US Department of Agriculture </p><p></p><p>Prion Inactivation and Environment </p><p></p><p>Principal Investigator: Dr. Mike Belosevic, University of Alberta </p><p></p><p>Co-Investigators: </p><p></p><p>Dr. Norman Neumann, University of Calgary </p><p></p><p>Dr. Neil Cashman, University of British Columbia </p><p></p><p>Dr. Daniel Smith, University of Alberta </p><p></p><p>Dr. Steven Craik, University of Alberta </p><p></p><p>Dr. Mohamed Gamal El-Din, University of Alberta </p><p></p><p>Dr. Phillip Fedorak, University of Alberta </p><p></p><p>Immunoprophylaxis of Bovine Spongiform Encephalopathy </p><p></p><p>Principal Investigator: Dr. Andrew A. Potter, University of Saskatchewan </p><p></p><p>Co-Investigators: </p><p></p><p>Dr. Philip Griebel, University of Saskatchewan </p><p></p><p>Dr. Scott Napper, University of Saskatchewan </p><p></p><p>Dr. Lorne Babiuk, University of Saskatchewan </p><p></p><p>Research Theme II: Chronic Wasting Disease </p><p></p><p>Theme Leader: Dr. Ted Leighton, University of Saskatchewan </p><p></p><p>Associate Theme Leader: Dr. Cheryl Waldner, University of Saskatchewan </p><p></p><p>Sub-Theme Leader (for Scrapie): Dr. Aru Balachandran, Canadian Food Inspection Agency </p><p></p><p>Factors Affecting Prevalence and Geographic Spread of Chronic Wasting Disease in </p><p></p><p>Wild Deer in Saskatchewan (Phase I & II) </p><p></p><p>Principal Investigator: Dr. Trent Bollinger, University of Saskatchewan </p><p></p><p>Co-Investigators: </p><p></p><p>Dr. Dave Coltman, University of Alberta </p><p></p><p>Dr. Ted Leighton, Canadian Cooperative Wildlife Health Centre, University of Saskatchewan </p><p></p><p>Dr. Francois Messier, University of Saskatchewan </p><p></p><p>Dr. Cheryl Waldner, Western College of Veterinary Medicine, University of Saskatchewan </p><p></p><p>A Comparative Approach Examining Host Response to TSE Infection by Serial Analysis </p><p></p><p>of Gene Expression (microSAGE) in Cervids and Ovids </p><p></p><p>Principal Investigator: Dr. Stephen Moore, University of Alberta </p><p></p><p>Co-Investigators: </p><p></p><p>Dr. Michael Brownstein, J. Craig Venter Institute </p><p></p><p>Dr. Mike Miller, Wildlife Research Centre, Colorado </p><p></p><p>Dr. Catherine Graham, Canadian Food Inspection Agency </p><p></p><p>Dr. Aru Balachandran, Canadian Food Inspection Agency </p><p></p><p>PrioNet's Research Projects Related to CWD & BSE </p><p></p><p>PrioNet Canada will address Canadian prion challenges through its five research themes. The </p><p></p><p>theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy </p><p></p><p>and Chronic Wasting Disease are outlined below: </p><p></p><p>Stay tuned to upcoming </p><p></p><p>issues of PrioNews as </p><p></p><p>we feature PrioNet's </p><p></p><p>three other research </p><p></p><p>themes: </p><p></p><p></p><p></p><p>==================================END </p><p></p><p></p><p></p><p>DNA polymorphisms of the prion doppel gene region in four different German </p><p>cattle breeds and cows tested positive for bovine spongiform encephalopathy </p><p></p><p>Journal Mammalian Genome </p><p>Publisher Springer New York </p><p>ISSN 0938-8990 (Print) 1432-1777 (Online) </p><p>Subject Biomedical and Life Sciences and Medicine </p><p>Issue Volume 16, Number 11 / November, 2005 </p><p>DOI 10.1007/s00335-005-0052-9 </p><p>Pages 884-892 </p><p>Online Date Saturday, November 12, 2005 </p><p></p><p></p><p>N. Balbus1, A. Humeny1, K. Kashkevich1, I. Henz1, C. Fischer2, C.-M. Becker1 </p><p>and K. Schiebel1 </p><p></p><p>(1) Institut für Biochemie, Emil-Fischer-Zentrum, Universität </p><p>Erlangen-Nürnberg, Fahrstrasse 17, 91054 , Erlangen, Germany </p><p>(2) Institut für Humangenetik, Universität Heidelberg, Im Neuenheimer Feld </p><p>366, 69120, Heidelberg, Germany </p><p></p><p>Received: 5 April 2005 Accepted: 18 July 2005 Published online: 11 </p><p>November 2005 </p><p></p><p>Abstract Polymorphisms of the prion protein gene PRNP have been shown to </p><p>influence the susceptibility/resistance to prion infections in human and </p><p>sheep. In addition, the T174M polymorphism within the flanking prion doppel </p><p>gene (PRND) was thought to be involved in susceptibility to sporadic </p><p>Creutzfeldt-Jacob disease. To study a possible influence of DNA </p><p>polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy </p><p>(BSE), previously identified and newly isolated DNA polymorphisms were </p><p>genotyped in all available German cattle that tested positive for BSE. </p><p>Genotypes and calculated haplotypes were compared with breeding bulls </p><p>serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein </p><p>Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh </p><p>(Swiss Brown) resulted in the isolation of the previously known </p><p>polymorphisms R50H and R132Q and two novel synonymous single nucleotide </p><p>polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype </p><p>analysis of BSE and control animals revealed a significantly different </p><p>distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not </p><p>in the other breeds tested. No association to BSE susceptibility was </p><p>detectable for polymorphisms R50H and A5063T. </p><p></p><p>---------------------------------------------------------------------------- </p><p>---- </p><p></p><p></p><p>K. Schiebel </p><p>Email: <a href="mailto:katrin.schiebel@biochem.uni-erlangen.de">katrin.schiebel@biochem.uni-erlangen.de</a> </p><p>Phone: 49-9131 85-26206 </p><p>Fax: 49-9131 85-22485 </p><p></p><p>References secured to subscribers. </p><p></p><p></p><p><a href="http://www.springerlink.com/content/y1222u1n55756w18/?p=9b0ad07fa1564bfba3e9c382a5cabec8&pi=7" target="_blank">http://www.springerlink.com/content/y12 ... abec8&pi=7</a> </p><p></p><p></p><p>Subject: Atypical BSE in Germany-Proof of transmissibility and biochemical </p><p>characterization </p><p>Date: August 20, 2006 at 3:33 pm PST </p><p>Copyright © 2006 Elsevier B.V. All rights reserved. </p><p></p><p>Atypical BSE in Germany-Proof of transmissibility and biochemical </p><p>characterization </p><p></p><p></p><p>A. Buschmanna, A. Gretzschela, A.-G. Biacabeb, K. Schiebelc, C. Coronad, C. </p><p>Hoffmanna, M. Eidena, T. Baronb, C. Casaloned and Martin H. Groschupa, , </p><p></p><p>aFriedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging </p><p>Infectious Diseases, Boddenblick 5a, 17493 Greifswald, Insel Riems, Germany </p><p>bAFSSA-Lyon, Unite ATNC, Lyon, France </p><p>cInstitut für Biochemie, Universitity Erlangen-Nürnberg, Germany </p><p>dCEA, Instituto Zooprofilattico di Turino, Turin, Italy </p><p></p><p>Received 11 January 2006; revised 23 May 2006; accepted 2 June 2006. </p><p>Available online 17 August 2006. </p><p></p><p></p><p></p><p>Abstract </p><p></p><p></p><p>Intensive active surveillance has uncovered two atypical German BSE cases in </p><p>older cattle which resemble the two different atypical BSE phenotypes that </p><p>have recently been described in France (designated H-type) and Italy </p><p>(designated L-type or BASE). The H-type is characterized by a significantly </p><p>higher molecular size, but a conventional glycopattern of the proteinase K </p><p>treated abnormal prion protein (PrPSc), while the L-type PrPSc has only a </p><p>slightly lower molecular size and a distinctly different glycopattern. In </p><p>this paper we describe the successful transmission of both German atypical </p><p>BSE cases to transgenic mice overexpressing bovine PrPC. Upon challenge with </p><p>the L-type, these mice developed BSE after a substantially shorter </p><p>incubation period than any classical BSE transmission using these mice to </p><p>date. In contrast, the incubation period was distinctly prolonged when these </p><p>mice were challenged with the H-type. PrPSc accumulated in the brains of </p><p>these mice were of the same atypical BSE type that had been used for the </p><p>transmission. These atypical cases suggest the possible existence of </p><p>sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in </p><p>the UK could have also been initiated by an intraspecies transmission from a </p><p>sporadic BSE case. </p><p></p><p>Keywords: BSE; Cattle; PrPSc; Biochemical differentiation </p><p></p><p></p><p></p><p></p><p><a href="http://www.sciencedirect.com/" target="_blank">http://www.sciencedirect.com/</a> </p><p></p><p></p><p></p><p>THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 280, NO. 45, pp. 37408–37414, November 11, 2005 </p><p></p><p>© 2005 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. </p><p></p><p></p><p></p><p>Bovine Prion Protein Gene (PRNP) Promoter Polymorphisms </p><p></p><p>Modulate PRNP Expression and May Be Responsible for </p><p></p><p>Differences in Bovine Spongiform Encephalopathy </p><p></p><p>Susceptibility*□S </p><p></p><p>Received for publication, June 10, 2005, and in revised form, July 20, 2005 Published, JBC Papers in Press, September 1, 2005, DOI 10.1074/jbc.M506361200 </p><p></p><p>Petra Sander‡, Henning Hamann‡, Cord Dro¨gemu¨ ller‡, Kseniya Kashkevich§, Katrin Schiebel§, and Tosso Leeb‡1 </p><p></p><p>From the ‡Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Bu¨nteweg 17p, 30559 Hannover, Germany </p><p></p><p>and the §Institute for Biochemistry, University of Erlangen-Nu¨rnberg, Fahrstrasse 17, 91054 Erlangen, Germany </p><p></p><p></p><p></p><p>The susceptibility of humans to the variant Creutzfeldt-Jakob </p><p></p><p>disease is greatly influenced by polymorphisms within the human </p><p></p><p>prion protein gene (PRNP). Similar genetic differences exist in </p><p></p><p>sheep, in which PRNP polymorphisms modify the susceptibility to </p><p></p><p>scrapie. However, the known coding polymorphisms within the </p><p></p><p>bovine PRNP gene have little or no effect on bovine spongiform </p><p></p><p>encephalopathy (BSE) susceptibility in cattle. We have recently </p><p></p><p>found a tentative association between PRNP promoter polymorphisms </p><p></p><p>and BSE susceptibility in German cattle (Sander, P., </p><p></p><p>Hamann, H., Pfeiffer, I., Wemheuer, W., Brenig, B., Groschup, M., </p><p></p><p>Ziegler, U., Distl, O., and Leeb, T. (2004) Neurogenetics 5, 19–25).A </p><p></p><p>plausible hypothesis explaining this observation could be that the </p><p></p><p>bovine PRNP promoter polymorphisms cause changes in PRNP </p><p></p><p>expression that might be responsible for differences in BSE incubation </p><p></p><p>time and/or BSE susceptibility. To test this hypothesis, we performed </p><p></p><p>a functional promoter analysis of the different bovine PRNP </p><p></p><p>promoter alleles by reporter gene assays in vitro and by measuring </p><p></p><p>PRNPmRNAlevels in calves with different PRNP genotypes in vivo. </p><p></p><p>Twovariable sites, a 23-bp insertion/deletion (indel) polymorphism </p><p></p><p>containing a RP58-binding site and a 12-bp indel polymorphism </p><p></p><p>containing an SP1-binding site, were investigated. Band shift assays </p><p></p><p>indicated differences in transcription factor binding to the different </p><p></p><p>alleles at the two polymorphisms. Reporter gene assays demonstrated </p><p></p><p>an interaction between the two postulated transcription factors and </p><p></p><p>lower expression levels of the ins/ins allele compared with the del/del </p><p></p><p>allele. The in vivo data revealed substantial individual variation of </p><p></p><p>PRNP expression in different tissues. In intestinal lymph nodes, </p><p></p><p>expression levels differed between the different PRNP genotypes. ...SNIP...END...TSS</p></blockquote><p></p>
[QUOTE="flounder, post: 272028, member: 3519"] The Genetic Approach to Controlling BSE By: David A. Rodger Stephen Moore was on holiday in his native Australia back in May 2003, when he received the telephone call that changed his life. “A Canadian reporter was on the line asking me to comment on a case of bovine spongiform encephalopathy (BSE) in Alberta,” says Dr. Moore “I still don’t know how he tracked me down. There wasn’t much I could say because, of course, this was news to me.” Back in Edmonton, where he is Chair of Bovine Genomics in the University of Alberta’s Department of Agricultural, Food and Nutritional Science, Dr. Moore was quickly brought up to date. He and his research group had been intimately involved in mapping the bovine genome and were considered leaders in identifying and characterizing genes that affect cattle growth, yield, fat content and meat tenderness. “There’s a genetic component in BSE susceptibility,” he explains. “You only have to look at the UK where some animals in a herd came down with the disease while others didn’t. This was despite their having eaten the same contaminated feed. What are the genetic factors that render cattle more susceptible or more resistant to BSE? The answers will help us with intervention, diagnosis, and treatment.” In January 2006, the Alberta Prion Research Institute appointed Dr. Moore its first scientific director. Dr. Moore also leads PrioNet’s Research Theme I on BSE. He is Principal Investigator on two APRI-PrioNet co-funded projects ...2 BSE - one related to BSE and the other to Chronic Wasting Disease. Other partners include the University of Alberta, National Microbiology Laboratories - Public Health Agency of Canada, National Centre for Foreign Animal Disease - Canadian Food Inspection Agency. “The only place in the world that has had a statistically significant number of BSE cases is the UK,” he says. “The number in Canada is, thankfully, too few for genetic analysis. So, two of my students went to the Rosslyn Institute in Scotland to extract DNA from the blood samples gathered from BSE-infected cattle. That trip was necessary because blood samples are infectious and can’t be brought into Canada, while DNA samples are harmless and can be imported. We’re now analyzing the DNA.” In late July 2006, another case of BSE was discovered, involving a 50-month old Alberta dairy cow born long after Canada’s ban on the use of cattle parts in cattle feed. How close is a test that detects BSE and other TSEs in live healthy animals? When will we be able to detect them in live animals as opposed to postmortem? “Before there can be a valid test - dozens are in trials now - two issues must be resolved,” says Dr. Moore. “First, it must be easy to collect a sample, and second, it can’t cost too much. If the test costs more than the animal is worth, it’s of little benefit to producers.” For more information visit the Alberta Prion Research Institute web site at [url=http://www.prioninstitute.ca]http://www.prioninstitute.ca[/url]. • Coming to terms with Chronic Wasting disease By: David A. Rodger PrioNet’s Scientific Director, Neil Cashman, has referred to chronic wasting disease (CWD) as “the threat in our own backyard.” Indeed, it could be the Transmissible Spongiform Encephalopathy with the greatest potential for species devastation. Leading PrioNet’s Theme 2 efforts to understand and control CWD is Ted Leighton of the Western College of Veterinary Medicine in Saskatoon. Dr. Leighton is recognized internationally for his research into wildlife diseases. So it will surprise many to discover that he did his undergraduate work at Cornell University not in science but in Theatre Arts. “Theatre Arts had liberal course requirements,” he explains, “enabling me to take natural science, social science and humanities in a mix that provided an excellent general education.” He received his veterinary degree from the University of Saskatchewan in 1979, completed a Ph.D. in veterinary pathology at Cornell in 1984, and returned to the University of Saskatchewan later that year as professor of veterinary pathology. Currently Dr. Leighton is Executive Director of the Canadian Cooperative Wildlife Health Centre, which is headquartered in Saskatoon. The organization is a partnership among Canada’s veterinary colleges and government agencies responsible for wildlife management, agriculture, and public health. The Centre’s mandate is one of disease surveillance. It has programs to monitor the occurrence and spread of such diseases as avian influenza, West Nile virus, and CWD (since 1997). CWD on elk farms in Saskatchewan and Alberta has been eradicated through a systematic program of culling infected or exposed animals. Unfortunately, CWD in wild animals, especially white-tailed and mule deer, is much harder to deal with. Two years ago, the Centre brought together international ...2 CWD experts in CWD, disease monitoring, deer biology, and other specialties to help determine whether CWD in wild deer in Canada represented a potential crisis. They determined that it does. “They told us Canada had a few years to develop its response to CWD,” he recalls, “because this is a slow-moving disease. They recommended that Canada take determined action to control the disease in wild deer, but warned that there were no proven methods of doing this and that scientific research carried out in the affected areas would have to guide any effective response. They emphasized that there would be large social, ecological or economic consequences for Canada if we do not stop the spread of CWD in wild deer.” Dr. Leighton praises the foresight that led to PrioNet’s creation, and the flexibility the network has been given to deal with a disease that was, until recently, overshadowed by BSE concerns in Canada. “Our priority with respect to CWD is to learn as much as we can about how it is transmitted. Only then can we develop a program to contain and eliminate it.” • Coming Together PrioNet established its Student and Young Professional Association (SYPA) at its recent Annual General Meeting 2006. Joel Watts and Qasim Khan (University of Toronto) are SYPA’s interim leaders. SYPA includes graduate students, post-doctoral fellows, research associates, and research technicians who are involved with PrioNet’s network investigators. The purpose of this association is to organize studentfocused events; liaise with PrioNet regarding issues surrounding students and young professionals; and work together to capitalize on the different programs PrioNet has available to strengthen their research and training experience. PrioNet will be implementing a variety of education and training programs to facilitate learning exchange and enrich the experience of students and young professionals within the network. For resources such as job postings and training updates related to students and young professionals, visit the Education and Training link at [url=http://www.prionetcanada.ca]http://www.prionetcanada.ca[/url]. • PrioNet’s Research Projects Related to CWD & BSE PrioNet Canada will address Canadian prion challenges through its five research themes. The theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy and Chronic Wasting Disease are outlined below: Research Theme I: Bovine Spongiform Encephalopathy Theme Leader: Dr. Steven Moore, University of Alberta Associate Leader: Dr. Mike Belosevic, University of Alberta Theme Pathologist: Dr. Stefanie Czub, Canadian Food Inspection Agency A Comprehensive and Comparative Approach to Genetics & Pathobiology of Prion Disease Principal Investigator: Dr. Steven Moore, University of Alberta Co-Investigators: Dr. John Williams, Parco Tecnologico Padano, Italy Dr. Michael Coulthart, Public Health Agency of Canada Dr. Denny Crews, Agriculture & Agri-food Canada Dr. Stefanie Czub, Canadian Food Inspection Agency Dr. Michael Heaton, US Department of Agriculture Prion Inactivation and Environment Principal Investigator: Dr. Mike Belosevic, University of Alberta Co-Investigators: Dr. Norman Neumann, University of Calgary Dr. Neil Cashman, University of British Columbia Dr. Daniel Smith, University of Alberta Dr. Steven Craik, University of Alberta Dr. Mohamed Gamal El-Din, University of Alberta Dr. Phillip Fedorak, University of Alberta Immunoprophylaxis of Bovine Spongiform Encephalopathy Principal Investigator: Dr. Andrew A. Potter, University of Saskatchewan Co-Investigators: Dr. Philip Griebel, University of Saskatchewan Dr. Scott Napper, University of Saskatchewan Dr. Lorne Babiuk, University of Saskatchewan Research Theme II: Chronic Wasting Disease Theme Leader: Dr. Ted Leighton, University of Saskatchewan Associate Theme Leader: Dr. Cheryl Waldner, University of Saskatchewan Sub-Theme Leader (for Scrapie): Dr. Aru Balachandran, Canadian Food Inspection Agency Factors Affecting Prevalence and Geographic Spread of Chronic Wasting Disease in Wild Deer in Saskatchewan (Phase I & II) Principal Investigator: Dr. Trent Bollinger, University of Saskatchewan Co-Investigators: Dr. Dave Coltman, University of Alberta Dr. Ted Leighton, Canadian Cooperative Wildlife Health Centre, University of Saskatchewan Dr. Francois Messier, University of Saskatchewan Dr. Cheryl Waldner, Western College of Veterinary Medicine, University of Saskatchewan A Comparative Approach Examining Host Response to TSE Infection by Serial Analysis of Gene Expression (microSAGE) in Cervids and Ovids Principal Investigator: Dr. Stephen Moore, University of Alberta Co-Investigators: Dr. Michael Brownstein, J. Craig Venter Institute Dr. Mike Miller, Wildlife Research Centre, Colorado Dr. Catherine Graham, Canadian Food Inspection Agency Dr. Aru Balachandran, Canadian Food Inspection Agency PrioNet’s Research Projects Related to CWD & BSE PrioNet Canada will address Canadian prion challenges through its five research themes. The theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy and Chronic Wasting Disease are outlined below: Stay tuned to upcoming issues of PrioNews as we feature PrioNet’s three other research themes: ==================================END DNA polymorphisms of the prion doppel gene region in four different German cattle breeds and cows tested positive for bovine spongiform encephalopathy Journal Mammalian Genome Publisher Springer New York ISSN 0938-8990 (Print) 1432-1777 (Online) Subject Biomedical and Life Sciences and Medicine Issue Volume 16, Number 11 / November, 2005 DOI 10.1007/s00335-005-0052-9 Pages 884-892 Online Date Saturday, November 12, 2005 N. Balbus1, A. Humeny1, K. Kashkevich1, I. Henz1, C. Fischer2, C.-M. Becker1 and K. Schiebel1 (1) Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054 , Erlangen, Germany (2) Institut für Humangenetik, Universität Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany Received: 5 April 2005 Accepted: 18 July 2005 Published online: 11 November 2005 Abstract Polymorphisms of the prion protein gene PRNP have been shown to influence the susceptibility/resistance to prion infections in human and sheep. In addition, the T174M polymorphism within the flanking prion doppel gene (PRND) was thought to be involved in susceptibility to sporadic Creutzfeldt-Jacob disease. To study a possible influence of DNA polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy (BSE), previously identified and newly isolated DNA polymorphisms were genotyped in all available German cattle that tested positive for BSE. Genotypes and calculated haplotypes were compared with breeding bulls serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh (Swiss Brown) resulted in the isolation of the previously known polymorphisms R50H and R132Q and two novel synonymous single nucleotide polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype analysis of BSE and control animals revealed a significantly different distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not in the other breeds tested. No association to BSE susceptibility was detectable for polymorphisms R50H and A5063T. ---------------------------------------------------------------------------- ---- K. Schiebel Email: [email=katrin.schiebel@biochem.uni-erlangen.de]katrin.schiebel@biochem.uni-erlangen.de[/email] Phone: 49-9131 85-26206 Fax: 49-9131 85-22485 References secured to subscribers. [url=http://www.springerlink.com/content/y1222u1n55756w18/?p=9b0ad07fa1564bfba3e9c382a5cabec8&pi=7]http://www.springerlink.com/content/y12 ... abec8&pi=7[/url] Subject: Atypical BSE in Germany-Proof of transmissibility and biochemical characterization Date: August 20, 2006 at 3:33 pm PST Copyright © 2006 Elsevier B.V. All rights reserved. Atypical BSE in Germany-Proof of transmissibility and biochemical characterization A. Buschmanna, A. Gretzschela, A.-G. Biacabeb, K. Schiebelc, C. Coronad, C. Hoffmanna, M. Eidena, T. Baronb, C. Casaloned and Martin H. Groschupa, , aFriedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging Infectious Diseases, Boddenblick 5a, 17493 Greifswald, Insel Riems, Germany bAFSSA-Lyon, Unite ATNC, Lyon, France cInstitut für Biochemie, Universitity Erlangen-Nürnberg, Germany dCEA, Instituto Zooprofilattico di Turino, Turin, Italy Received 11 January 2006; revised 23 May 2006; accepted 2 June 2006. Available online 17 August 2006. Abstract Intensive active surveillance has uncovered two atypical German BSE cases in older cattle which resemble the two different atypical BSE phenotypes that have recently been described in France (designated H-type) and Italy (designated L-type or BASE). The H-type is characterized by a significantly higher molecular size, but a conventional glycopattern of the proteinase K treated abnormal prion protein (PrPSc), while the L-type PrPSc has only a slightly lower molecular size and a distinctly different glycopattern. In this paper we describe the successful transmission of both German atypical BSE cases to transgenic mice overexpressing bovine PrPC. Upon challenge with the L-type, these mice developed BSE after a substantially shorter incubation period than any classical BSE transmission using these mice to date. In contrast, the incubation period was distinctly prolonged when these mice were challenged with the H-type. PrPSc accumulated in the brains of these mice were of the same atypical BSE type that had been used for the transmission. These atypical cases suggest the possible existence of sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in the UK could have also been initiated by an intraspecies transmission from a sporadic BSE case. Keywords: BSE; Cattle; PrPSc; Biochemical differentiation [url=http://www.sciencedirect.com/]http://www.sciencedirect.com/[/url] THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 280, NO. 45, pp. 37408–37414, November 11, 2005 © 2005 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. Bovine Prion Protein Gene (PRNP) Promoter Polymorphisms Modulate PRNP Expression and May Be Responsible for Differences in Bovine Spongiform Encephalopathy Susceptibility*□S Received for publication, June 10, 2005, and in revised form, July 20, 2005 Published, JBC Papers in Press, September 1, 2005, DOI 10.1074/jbc.M506361200 Petra Sander‡, Henning Hamann‡, Cord Dro¨gemu¨ ller‡, Kseniya Kashkevich§, Katrin Schiebel§, and Tosso Leeb‡1 From the ‡Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Bu¨nteweg 17p, 30559 Hannover, Germany and the §Institute for Biochemistry, University of Erlangen-Nu¨rnberg, Fahrstrasse 17, 91054 Erlangen, Germany The susceptibility of humans to the variant Creutzfeldt-Jakob disease is greatly influenced by polymorphisms within the human prion protein gene (PRNP). Similar genetic differences exist in sheep, in which PRNP polymorphisms modify the susceptibility to scrapie. However, the known coding polymorphisms within the bovine PRNP gene have little or no effect on bovine spongiform encephalopathy (BSE) susceptibility in cattle. We have recently found a tentative association between PRNP promoter polymorphisms and BSE susceptibility in German cattle (Sander, P., Hamann, H., Pfeiffer, I., Wemheuer, W., Brenig, B., Groschup, M., Ziegler, U., Distl, O., and Leeb, T. (2004) Neurogenetics 5, 19–25).A plausible hypothesis explaining this observation could be that the bovine PRNP promoter polymorphisms cause changes in PRNP expression that might be responsible for differences in BSE incubation time and/or BSE susceptibility. To test this hypothesis, we performed a functional promoter analysis of the different bovine PRNP promoter alleles by reporter gene assays in vitro and by measuring PRNPmRNAlevels in calves with different PRNP genotypes in vivo. Twovariable sites, a 23-bp insertion/deletion (indel) polymorphism containing a RP58-binding site and a 12-bp indel polymorphism containing an SP1-binding site, were investigated. Band shift assays indicated differences in transcription factor binding to the different alleles at the two polymorphisms. Reporter gene assays demonstrated an interaction between the two postulated transcription factors and lower expression levels of the ins/ins allele compared with the del/del allele. The in vivo data revealed substantial individual variation of PRNP expression in different tissues. In intestinal lymph nodes, expression levels differed between the different PRNP genotypes. ...SNIP...END...TSS [/QUOTE]
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