Subject: A major genetic component of BSE susceptibility
Date: October 17, 2006 at 2:05 pm PST
Research article
A major genetic component of BSE susceptibility
Katrin Juling*1, Hermann Schwarzenbacher1, John L Williams2,3 and
Ruedi Fries1
Address: 1Chair of Animal Breeding, Technical University of Munich, Hochfeldweg 1, 85354 Freising-Weihenstephan, Germany, 2Division of
Genetics and Genomics, Roslin Institute, Roslin, Midlothian EH25 9PS, UK and 3CERSA, Parco Tecnologico Padano, Via Einstein 26900 Lodi, Italy
Email: Katrin Juling* - [email protected]; Hermann Schwarzenbacher - [email protected];
John L Williams - [email protected]; Ruedi Fries - [email protected]
* Corresponding author
Abstract
Background: Coding variants of the prion protein gene (PRNP) have been shown to be major
determinants for the susceptibility to transmitted prion diseases in humans, mice and sheep.
However, to date, the effects of polymorphisms in the coding and regulatory regions of bovine
PRNP on bovine spongiform encephalopathy (BSE) susceptibility have been considered marginal or
non-existent. Here we analysed two insertion/deletion (indel) polymorphisms in the regulatory
region of bovine PRNP in BSE affected animals and controls of four independent cattle populations
from UK and Germany.
Results: In the present report, we show that two previously reported 23- and 12-bp insertion/
deletion (indel) polymorphisms in the regulatory region of bovine PRNP are strongly associated
with BSE incidence in cattle. Genotyping of BSE-affected and control animals of UK Holstein,
German Holstein, German Brown and German Fleckvieh breeds revealed a significant
overrepresentation of the deletion alleles at both polymorphic sites in diseased animals (P = 2.01
× 10-3 and P = 8.66 × 10-5, respectively). The main effect on susceptibility is associated with the 12-
bp indel polymorphism. Compared with non-carriers, heterozygous and homozygous carriers of
the 12-bp deletion allele possess relatively higher risks of having BSE, ranging from 1.32 to 4.01 and
1.74 to 3.65 in the different breeds. These values correspond to population attributable risks
ranging from 35% to 53%.
Conclusion: Our results demonstrate a substantial genetic PRNP associated component for BSE
susceptibility in cattle. Although the BSE risk conferred by the deletion allele of the 12-bp indel in
the regulatory region of PRNP is substantial, the main risk factor for BSE in cattle is environmental,
i.e. exposure to feedstuffs contaminated with the infectious agent.
snip...
Conclusion
In this study we presented significant association between
PRNP promoter indel polymorphisms and the BSE status
in three of four investigated cattle populations (Figure 1,
Table 1 and Table 2). We conclude that the main effect on
BSE susceptibility seems to result from the 12-bp indel.
The causality of either or both polymorphism cannot be
verified in this study, however our data highlight that the
12 bp deletion allele is associated with increased risk for
an animal to succumb to feed-borne BSE (Table 4 and Figure
4). Thus, our findings show a substantial genetic component
for the susceptibility of cattle to BSE, conferred by
variants in the regulatory region of PRNP, a gene that has
been shown to be involved in prion disease susceptibility/
resistance in other species. However, the different dimensions
of the BSE epidemic in UK and Germany, on the one
hand, and the similar frequencies of the PRNP-associated
susceptibility alleles in UK and German cattle, on the
other, indicate, that the main BSE risk factor for cattle is
environmental, i.e. exposure to contaminated feed, and
not genetic.
SEE FULL TEXT ;
http://www.biomedcentral.com/content/pdf/1741-7007-4-33.pdf
TSS
Date: October 17, 2006 at 2:05 pm PST
Research article
A major genetic component of BSE susceptibility
Katrin Juling*1, Hermann Schwarzenbacher1, John L Williams2,3 and
Ruedi Fries1
Address: 1Chair of Animal Breeding, Technical University of Munich, Hochfeldweg 1, 85354 Freising-Weihenstephan, Germany, 2Division of
Genetics and Genomics, Roslin Institute, Roslin, Midlothian EH25 9PS, UK and 3CERSA, Parco Tecnologico Padano, Via Einstein 26900 Lodi, Italy
Email: Katrin Juling* - [email protected]; Hermann Schwarzenbacher - [email protected];
John L Williams - [email protected]; Ruedi Fries - [email protected]
* Corresponding author
Abstract
Background: Coding variants of the prion protein gene (PRNP) have been shown to be major
determinants for the susceptibility to transmitted prion diseases in humans, mice and sheep.
However, to date, the effects of polymorphisms in the coding and regulatory regions of bovine
PRNP on bovine spongiform encephalopathy (BSE) susceptibility have been considered marginal or
non-existent. Here we analysed two insertion/deletion (indel) polymorphisms in the regulatory
region of bovine PRNP in BSE affected animals and controls of four independent cattle populations
from UK and Germany.
Results: In the present report, we show that two previously reported 23- and 12-bp insertion/
deletion (indel) polymorphisms in the regulatory region of bovine PRNP are strongly associated
with BSE incidence in cattle. Genotyping of BSE-affected and control animals of UK Holstein,
German Holstein, German Brown and German Fleckvieh breeds revealed a significant
overrepresentation of the deletion alleles at both polymorphic sites in diseased animals (P = 2.01
× 10-3 and P = 8.66 × 10-5, respectively). The main effect on susceptibility is associated with the 12-
bp indel polymorphism. Compared with non-carriers, heterozygous and homozygous carriers of
the 12-bp deletion allele possess relatively higher risks of having BSE, ranging from 1.32 to 4.01 and
1.74 to 3.65 in the different breeds. These values correspond to population attributable risks
ranging from 35% to 53%.
Conclusion: Our results demonstrate a substantial genetic PRNP associated component for BSE
susceptibility in cattle. Although the BSE risk conferred by the deletion allele of the 12-bp indel in
the regulatory region of PRNP is substantial, the main risk factor for BSE in cattle is environmental,
i.e. exposure to feedstuffs contaminated with the infectious agent.
snip...
Conclusion
In this study we presented significant association between
PRNP promoter indel polymorphisms and the BSE status
in three of four investigated cattle populations (Figure 1,
Table 1 and Table 2). We conclude that the main effect on
BSE susceptibility seems to result from the 12-bp indel.
The causality of either or both polymorphism cannot be
verified in this study, however our data highlight that the
12 bp deletion allele is associated with increased risk for
an animal to succumb to feed-borne BSE (Table 4 and Figure
4). Thus, our findings show a substantial genetic component
for the susceptibility of cattle to BSE, conferred by
variants in the regulatory region of PRNP, a gene that has
been shown to be involved in prion disease susceptibility/
resistance in other species. However, the different dimensions
of the BSE epidemic in UK and Germany, on the one
hand, and the similar frequencies of the PRNP-associated
susceptibility alleles in UK and German cattle, on the
other, indicate, that the main BSE risk factor for cattle is
environmental, i.e. exposure to contaminated feed, and
not genetic.
SEE FULL TEXT ;
http://www.biomedcentral.com/content/pdf/1741-7007-4-33.pdf
TSS