The prion protein (PrP) gene modulates the incidence and incubation periods of transmissible spongiform encephalopathies of sheep, goats, mice and man. Here, a new caprine PrP allele encoding the shortest naturally occurring PrP protein so far described is reported. This variant contains only three instead of the usual five copies of a short peptide repeat [Pro-Gln/His-Gly-Gly-Gly-(Gly)-Trp- Gly-Gln] characteristic of PrP, with an additional Trp to Gly substitution in codon 102. Fifteen out of 111 genotyped goats carried the novel PrP allele and 14 survived without signs of disease for at least 4 years. One goat heterozygous for the polymorphism was challenged experimentally with SSBP/1-scrapie and succumbed after an unusually long incubation period.
BrownP.1994; Transmissible human spongiform encephalopathy (infectious cerebral amyloidosis): Creutzfeldt-lakob disease, Gerstmann- Straussler-Scheinker syndrome, and Kuru. In Neurodegenerative Diseases pp 839–876CalneD. B.
Edited by Philadelphia: W. B. Saunders;
BrownD. R.,
QinK.,
HermsJ. W.,
MadlungA.,
MansonJ.,
StromeR.,
FraserP. E.,
KruckT.,
von BohlensA.,
Schulz-SchaefferW.,
GieseA.,
WestawayD.,
KretzschmarH.1997; The cellular prion protein binds copper in vivo
. Nature 390:684–687
CervenakovaL.,
BrownP.,
NagleJ.,
GoldfarbL. G.,
GajdusekD. C.1994; R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD). American Journal of Human Genetics 55:3
ChenS. G.,
TeplowD. B.,
ParchiP.,
TellerJ. K.,
GambettiP.,
AutiliogambettiL.1995; Truncated forms of the human prion protein in normal brain and in prion diseases. Journal of Biological Chemistry 270:19173–19180
DiedrichJ. F.,
KnopmanD. S.,
ListJ. F.,
OlsonK.,
FreyW. H.IIEmoryC. R.,
SungJ. H.,
HaaseA. T.1992; Deletion in the prion protein gene in a demented patient. Human Molecular Genetics 1:443–444
FarquharC. F.,
SomervilleR. A.,
RitchieL. A.1989; Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy. Journal of Virological Methods 24:215–221
GoldfarbL. G.,
BrownP.,
McCombieW. R.,
GoldgaberD.,
SwergoldG. D.,
WillsP. R.,
CervenakovaL.,
BaronH.,
GibbsC. J.Jr1991; Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. roceedings of the National Academy of Sciences, USA 88:10926–10930
GoldmannW.,
HunterN.,
FosterJ. D.,
SalbaumJ. M.,
BeyreutherK.,
HopeJ.1990; Two alleles of a neural protein gene linked to scrapie in sheep. Proceedings of the National Academy of Sciences, USA 87:2476–2480
GoldmannW.,
HunterN.,
MartinT.,
DawsonM.,
HopeJ.1991; Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. Journal of General Virology 72:201–204
GoldmannW.,
MartinT.,
FosterJ.,
HughesS.,
SmithG.,
HughesK.,
DawsonM.,
HunterN.1996; Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period. Journal of General Virology 77:2885–2891
HopeJ.,
MortonL. J. D.,
FarquharC. F.,
MulthaupG.,
BeyreutherK.,
KimberlinR. H.1986; The major polypeptide of scrapie- associated fibrils (SAF) has the same size, charge- distribution and N- terminal protein-sequence as predicted for the normal brain protein (PrP). EMBO Journal 5:2591–2597
HornshawM. P.,
McDermottJ. R.,
CandyJ. M.1995; Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochemical and Biophysical Research Communications 207:621–629
HunterN.1997; Molecular biology and genetics of scrapie in sheep. In The Genetics of Sheep pp 225–240PiperL.,
RuvinskyA.
Edited by Wallingford, UK: CAB International;
HunterN.,
GoldmannW.,
SmithG.,
HopeJ.1994; Frequencies of PrP gene variants in healthy cattle and cattle with BSE in Scotland. Veterinary Record 135:400–403
HunterN.,
FosterJ. D.,
GoldmannW.,
StearM.,
HopeJ.,
BostockC.1996; Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology 141:809–824
KretzschmarH.,
StowringL. E.,
WestawayD.,
StubblebineW. H.,
PrusinerS. B.,
DeArmondS. B.1986; Molecular cloning of a human prion protein cDNA. DNA 5:315–324
LaplancheJ. L.,
Delasnerie-LaupretreN.,
BrandelJ. P.,
DussaucyM.,
ChatelainJ.,
LaunayJ. M.1995; Two novel insertions in the prion protein gene in patients with late-onset dementia. Human Molecular Genetics 4:1109–1111
MansonJ. C.,
ClarkeA. R.,
McBrideP. A.,
McConnellI.,
HopeJ.1994; PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegeneration 3:331–340
PalmerM. S.,
MahalS. P.,
CampbellT. A.,
HillA. F.,
SidleK. C.,
LaplancheJ.-L.,
CollingeJ.1993; Deletions in the prion protein gene are not associated with CJD. Human Molecular Genetics 2:541–544
SchätzlH. M.,
DaCostaM.,
TaylorL.,
CohenF. E.,
PrusinerS. B.1995; Prion protein gene variation among primates. Journal of Molecular Biology 245:362–374
VitalC.,
GrayF.,
VitalA.,
ParchiP.,
CapellariS.,
PetersenR. B.,
FerrerX.,
JarnierD.,
JulienJ.,
GambettiP.1998; Prion encephalopathy with insertion of octapeptide repeats : the number of repeats determines the type of cerebellar deposits. Neuropathology and Applied Neurobiology 24:125–130
WoodJ. N. L.,
DoneS. H.,
PritchardG. C.,
WooldridgeM. J. A.1992; Natural scrapie in goats : case histories and clinical signs. Veterinary Record 131:66–68