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From: TSS ()
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 www.prioninstitute.ca. • 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 www.prionetcanada.ca. • 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 Journal Mammalian Genome (1) Institut für Biochemie, Emil-Fischer-Zentrum, Universität Received: 5 April 2005 Accepted: 18 July 2005 Published online: 11 Abstract Polymorphisms of the prion protein gene PRNP have been shown to ---------------------------------------------------------------------------- References secured to subscribers. Atypical BSE in Germany-Proof of transmissibility and biochemical aFriedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging Received 11 January 2006; revised 23 May 2006; accepted 2 June 2006. Abstract Keywords: BSE; Cattle; PrPSc; Biochemical differentiation 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
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