Arch Virol (2007) DOI 10.1007/s00705-007-0956-7 Printed in The Netherlands Rapid Communication Which PrP haplotypes in a French sheep population are the most susceptible to atypical scrapie? C. R. Moreno, K. Moazami-Goudarzi, P. Laurent, G. Cazeau, O. Andreoletti, S. Chadi, J.-M. Elsen, and D. Calavas INRA – Institut National Recherche Agronomique, Stadion d’Amelioration Genetique des Animaux, Castanet-Tolosan, France Received August 11, 2006; accepted February 7, 2007; published online April 12, 2007 # Springer-Verlag 2007 Summary A French sheep case control study has been orga- nised to estimate the effects of the PrP haplotypes on resistance to atypical scrapie. The ALHQ and AFRQ haplotypes are significantly more suscepti- ble than the others. Scrapie is a transmissible spongiform encephalop- athy (TSE) of small ruminants. TSEs are charac- terised by the accumulation of an abnormal form of a host-encoded protein in the central nervous sys- tem of affected individuals (normal and abnormal forms are denoted PrP and PrPsc, respectively) [12]. In sheep, susceptibility to scrapie has been largely proven to be controlled by polymorphisms of the PRNP gene at codons 136, 154 and 171, with a high resistance of the ARR carriers to the classi- cal form of scrapie [5, 8]. However, in 1998, a new type of scrapie was discovered in Norway (Nor98) [2]. Since the imple- mentation of the active TSE surveillance program in EU member states, so-called atypical cases have been observed in most of the countries participating to the program [3, 4, 6]. Atypical scrapie can be distinguished from classical scrapie by a Western blot PrPsc signature similar to that observed in Nor98 [2]. Amongst the atypical Norwegian scrapie cases, there was a large proportion of A 136 H 154 Q 171 haplotype carriers as well as A 136 F 141 R 154 Q 171 hap- lotype carriers [10]. From January 2002 to June 2006, 118 atypical scrapie cases were detected by active surveillance in France. In these animals, a direct sequencing of PrP gene was performed. A 573-bp fragment of the coding region of the PRP gene, encompassing co- dons 92–282, was amplified via PCR for all DNA samples with primers F294: 5 0 -AGGCTGGGGT CAAGGTGGTAGC-3 0 and 56R: 5 0 -TACAGGGC TGCAGGTAGACA-3 0 [10]. PCR products were sequenced with nested primer PRP1.F: 5 0 -GTCA AGGTGGTAGCCACAG-3 0 for the sense sequenc- ing and PRP1.R: 5 0 -CATTATCTTCTTAATCTTT GCC-3 0 for the reverse sense (531-bp fragment). PCR products were sequenced with the Dynamic ET Terminator chemistry using the Megabase au- Author’s address: Dr. Carole Moreno, INRA – Institut National Recherche Agronomique, Stadion d’Amelioration, Genetique des Animaux BP 27, 31326 Castanet-Tolosan, France. e-mail: moreno@toulouse.inra.fr