Quantitative estimation of genetic risk for atypical scrapie in French sheep and potential consequences of the current breeding programme for resistance to scrapie on the risk of atypical scrapie

We obtained genotypes at codons 136, 141, 154 and 171 of the PRNP gene for representative samples of 248 AS and 245 CS cases. We used a random sample of 3,317 scrapie negative animals genotyped at codons 136, 154 and 171 and we made inferences on the position 141 by multiple imputations, using external data. To estimate the risk associated with PrP genotypes, we fitted multivariate logistic regression models and we estimated the prevalence of AS for the different genotypes. Then, we used the risk of AS estimated for the ALRR-ALRR genotype to analyse the risk of detecting an AS case in a flock homogenous for this genotype.Genotypes most at risk for AS were those including an AFRQ or ALHQ allele while genotypes including a VLRQ allele were less commonly associated with AS. Compared to ALRQ-ALRQ, the ALRR-ALRR genotype was significantly at risk for AS and was very significantly protective for CS. The prevalence of AS among ALRR-ALRR animals was 0.6‰ and was not different from the prevalence in the general population.In conclusion, further selection of ALRR-ALRR animals will not result in an overall increase of AS prevalence in the French sheep population although this genotype is clearly susceptible to AS. However the probability of detecting AS cases in flocks participating in genetic breeding programme against CS should be considered.Bovine spongiform encephalopathy (BSE) is a zoonotic transmissible spongiform encephalopathy (TSE), which may have spread to sheep and goat populations. This situation has prompted European countries to organise control and surveillance of TSEs in small ruminants in which BSE cannot be clinically distinguished from scrapie.In sheep, genetic susceptibility to classical scrapie (CS) is supported by polymorphic variations at codons 136, 154 and 171 of the PRNP gene, which encodes the normal cellular protein prion (PrPC) [1]. The main alleles defined by these three codons can be classified by increasing risk as follows ARR < AHQ < ARQ ≈ ARH