Prevalence of the prion protein gene E211K variant in U.S. cattle

Research Project:

Haplotype Structure of the Bovine Prion Gene Complex and Association with Bovine Spongiform Encephalopathy (Bse) Location: Animal Health Systems Research

Title: Prevalence of the prion gene E211K variant in U.S. cattle

Authors

Heaton, Michael Keele, John Harhay, Gregory Richt, Juergen Koohmaraie, Mohammad Wheeler, Tommy Shackelford, Steven Casas, Eduardo King, David Sonstegard, Tad Van Tassell, Curtis Neibergs, Holly - WASHINGTON STATE UNIV. Chase, Chadwick Kalbfleisch, Ted - UNIV. OF LOUISVILLE, KY Smith, Timothy Clawson, Michael Laegreid, William - FORMER ARS EMPLOYEE

Submitted to: BioMed Central (BMC) Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: June 10, 2008 Publication Date: July 14, 2008 Citation: Heaton, M.P., Keele, J.W., Harhay, G.P., Richt, J., Koohmaraie, M., Wheeler, T.L., Shackelford, S.D., Casas, E., King, D.A., Sonstegard, T.S., Van Tassell, C.P., Neibergs, H.L., Chase, C.C., Kalbfleisch, T.S., Smith, T.P., Clawson, M.L., Laegreid, W.W. 2008. Prevalence of the prion gene E211K variant in U.S. cattle. BioMed Central (BMC) Veterinary Research 4:25. (http://www.biomedcentral.com/1746-6148/4/25)

Interpretive Summary: Classical bovine spongiform encephalopathy (BSE) is a transmissible fatal brain-wasting disease in cattle. Also known as "mad cow disease," it was first diagnosed in 1986, in the United Kingdom (UK). BSE has since been found in 24 countries including Japan, Canada, and the United States. Consumption of contaminated beef from BSE-affected animals in the UK has been implicated as the most likely cause of a similar disease in humans, variant Creutzfeldt-Jakob Disease (vCJD). However, after regulations were put in place to prevent BSE-contaminated tissues from entering the feed supply and active BSE surveillance was increased, the number of BSE cases dropped dramatically. This was followed by a corresponding reduction in human vCJD cases. A rare type of BSE in cattle, referred to as ¿atypical BSE,¿ has recently been identified and is of interest because it develops in older animals without apparent exposure to other BSE-contaminated material. Although only 30 atypical BSE cases have been identified worldwide, they are significant because of their possible link to other CJDs in humans (i.e., other than vCJD). In 2006, a U.S. case of atypical BSE was discovered in Alabama and later reported to have a mutation (E211K) in the bovine gene required for BSE (i.e., the prion gene). This bovine mutation is strikingly similar to the most commonly inherited defect in humans that causes a type of CJD to develop late in life. This may imply that older cattle with the E211K mutation may also develop atypical BSE late in life. To determine whether this DNA mutation is rare in U.S. cattle, an accurate test was developed and more than 5500 cattle from all parts of the beef and dairy industry were tested for the presence of the mutation. This represents the first prevalence estimate of a mutation that may cause atypical BSE in older animals without prior exposure to BSE-contaminated tissues. None of the cattle tested were found to have the E211K mutation. Thus, the mutation appears to be either exceedingly rare or non-existent among U.S. purebred, crossbred, beef, and dairy cattle.


Technical Abstract: Background: In 2006, an atypical U.S. case of bovine spongiform encephalopathy (BSE) was discovered in Alabama and later reported to be polymorphic for glutamate (E) and lysine (K) codons at position 211 in the bovine prion gene (PRNP) coding sequence. A bovine E211K mutation is important because it is analogous to the most common pathogenic mutation in humans (E200K) which causes hereditary Creutzfeldt - Jakob disease, an autosomal dominant form of prion disease. The present report describes a high-throughput matrix-associated laser desorption/ionization-time-of-flight mass spectrometry assay for scoring the PRNP E211K variant and its use to determine an upper limit for the K211 allele prevalence in U.S. cattle. Results: The K211 allele was not detected in 5690 cattle, including those from five commercial beef processing plants in three states (3892 carcasses) and 1798 registered cattle from 33 breeds. Nearby polymorphisms in PRNP coding sequence of 1084 diverse purebred cattle (33 breeds) did not interfere with scoring E211 or K211 alleles. Based on these results, the prevalence of the E211K variant was estimated to be extremely low, less than 1 in 1900 cattle (Bayesian analysis based on 95% quantile of the posterior distribution with a uniform prior). Conclusion: No groups or breeds of U.S. cattle are presently known to harbor the PRNP K211 variant. Consequently, high-throughput DNA testing may be required to identify carriers and further evaluate this allele as a risk factor for atypical BSE.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=223296


Prevalence of the prion protein gene E211K variant in U.S. cattle
Michael P Heaton , John W Keele , Gregory P Harhay , Jurgen A Richt , Mohammad Koohmaraie , Tommy L Wheeler , Steven D Shackelford , Eduardo Casas , D ANDY King , Tad S Sonstegard , Curtis P Van Tassell , Holly L Neibergs , Chad C Chase Jr. , Theodore S Kalbfleisch. , Timothy PL Smith , Michael L Clawson and William W Laegreid

BMC Veterinary Research 2008, 4:25doi:10.1186/1746-6148-4-25


Published: 14 July 2008


Abstract (provisional)
Background
In 2006, an atypical U.S. case of bovine spongiform encephalopathy (BSE) was discovered in Alabama and later reported to be polymorphic for glutamate (E) and lysine (K) codons at position 211 in the bovine prion protein gene (Prnp) coding sequence. A bovine E211K mutation is important because it is analogous to the most common pathogenic mutation in humans (E200K) which causes hereditary Creutzfeldt - Jakob disease, an autosomal dominant form of prion disease. The present report describes a high-throughput matrix-associated laser desorption/ionization-time-of-flight mass spectrometry assay for scoring the Prnp E211K variant and its use to determine an upper limit for the K211 allele frequency in U.S. cattle.

Results
The K211 allele was not detected in 6062 cattle, including those from five commercial beef processing plants (3892 carcasses) and 2170 registered cattle from 42 breeds. Multiple nearby polymorphisms in Prnp coding sequence of 1456 diverse purebred cattle (42 breeds) did not interfere with scoring E211 or K211 alleles. Based on these results, the upper bounds for prevalence of the E211K variant was estimated to be extremely low, less than 1 in 2000 cattle (Bayesian analysis based on 95% quantile of the posterior distribution with a uniform prior).

Conclusion
No groups or breeds of U.S. cattle are presently known to harbor the Prnp K211 allele. Because a carrier was not detected, the number of additional atypical BSE cases with K211 will also be vanishingly low.



http://www.biomedcentral.com/1746-6148/4/25


http://www.biomedcentral.com/content/pdf/1746-6148-4-25.pdf



> This represents the first prevalence estimate of a mutation that may cause atypical BSE in older animals without prior exposure to BSE-contaminated tissues.

i seriously doubt that statement. check out the tonnage of mad cow tainted feed in Alabama as late as 2006, IN COMMERCE.

this spontaneous atypical bse (THAT LOOKS LIKE HUMAN SPORADIC CJD) old cow theory is just more BSe. ...TSS



Subject: MAD COW FEED RECALL USA SEPT 6, 2006 1961.72 TONS IN COMMERCE AL, TN, AND WV Date: September 6, 2006 at 7:58 am PST

REASON Dairy and poultry feeds were possibly contaminated with ruminant based protein. VOLUME OF PRODUCT IN COMMERCE 477.72 tons DISTRIBUTION AL

VOLUME OF PRODUCT IN COMMERCE 1,484 tons DISTRIBUTION TN and WV

http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html


______________________________

PRODUCT

Bulk custom dairy pre-mixes, Recall # V-120-6

CODE
None

RECALLING FIRM/MANUFACTURER

Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm
initiated recall is complete.

REASON

Possible contamination of dairy animal feeds with ruminant derived meat and
bone meal.

VOLUME OF PRODUCT IN COMMERCE

350 tons

DISTRIBUTION

AL and MS

______________________________


PRODUCT

a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet,
50 lb. bags, Recall # V-121-6;
b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet,
50 lb. bags, Recall # V-122-6;
c) Tucker Milling, LLC #31232 Game Bird Grower,
50 lb. bags, Recall # V-123-6;
d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD
Medicated, 50 lb bags, Recall # V-124-6;
e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags,
Recall # V-125-6;
f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags,
Recall # V-126-6;
g) Tucker Milling, LLC #30116, TM Broiler Finisher,
50 lb bags, Recall # V-127-6

CODE

All products manufactured from 02/01/2005 until 06/20/2006

RECALLING FIRM/MANUFACTURER

Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit
on June 20, 2006, and by letter on June 23, 2006.
Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated
recall is ongoing.

REASON

Poultry and fish feeds which were possibly contaminated with ruminant based
protein were not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE

7,541-50 lb bags

DISTRIBUTION

AL, GA, MS, and TN

END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006

###


http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html


Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125
TONS Products manufactured from 02/01/2005 until 06/06/2006

Date: August 6, 2006 at 6:16 pm PST

PRODUCT

a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated,
net wt. 50 lbs, Recall # V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated,
Recall # V-103-6;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend,
Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted,
Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020,
Carbadox -- 0.0055%, Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete
Feed for Chickens from Hatch to 20 Weeks, Medicated,
Bacitracin Methylene Disalicylate, 25 and 50 Lbs,
Recall # V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying
Chickens, Recall # 108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED,
net wt 50 Lbs, Recall # V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs,
Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs,
Recall # V-112-6

CODE

Product manufactured from 02/01/2005 until 06/06/2006

RECALLING FIRM/MANUFACTURER

Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and
visit on June 9, 2006. FDA initiated recall is complete.

REASON

Animal and fish feeds which were possibly contaminated with ruminant based
protein not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE

125 tons

DISTRIBUTION

AL and FL


END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006

###


http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html



MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE

Sun Jul 16, 2006 09:22

71.248.128.67


RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II

______________________________


PRODUCT


a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals,
Recall # V-079-6;
b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg),
Recall # V-080-6;
c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL
FEED, Recall # V-081-6;
d) Feather Meal, Recall # V-082-6
CODE
a) Bulk
b) None
c) Bulk
d) Bulk

RECALLING FIRM/MANUFACTURER

H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and
by press release on June 16, 2006. Firm initiated recall is ongoing.

REASON

Possible contamination of animal feeds with ruminent derived meat and bone
meal.

VOLUME OF PRODUCT IN COMMERCE

10,878.06 tons

DISTRIBUTION

Nationwide

END OF ENFORCEMENT REPORT FOR July 12, 2006

###



http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html



Wednesday, July 16, 2008

Implementation of 2008 Feed Ban Enhancements Questions and Answers July 15, 2008

http://madcowfeed.blogspot.com/2008/07/implementation-of-2008-feed-ban.html



Thursday, July 10, 2008
A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html



Thursday, July 10, 2008
A New Prionopathy update July 10, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html



SEAC Draft minutes of the 100th meeting held on 25th April 2008

http://seac992007.blogspot.com/2008/07/seac-draft-minutes-of-100th-meeting.html



HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html




PEACE


Terry S. Singeltary Sr. P.O. Box 42 Baycliff, Texas USA 77518