title: 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.
abstract: BACKGROUND
  Since 2002, active surveillance programmes have detected numerous atypical scrapie (AS) and classical scrapie cases (CS) in French sheep with almost all the PrP genotypes. The aim of this study was 1) to quantify the genetic risk of AS in French sheep and to compare it with the risk of CS, 2) to quantify the risk of AS associated with the increase of the ARR allele frequency as a result of the current genetic breeding programme against CS.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 per thousand and was not different from the prevalence in the general population.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INRA, Centre de Clermont-Theix, 63122 Saint Genès Champanelle, France. alexandre.fediaevsky@agriculture.gouv.fr
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fediaevsky
authors.forename: Didier
authors.initials: D
authors.lastname: Calavas
authors.forename: Patrick
authors.initials: P
authors.lastname: Gasqui
authors.forename: Katayoun
authors.initials: K
authors.lastname: Moazami-Goudarzi
authors.forename: Pascal
authors.initials: P
authors.lastname: Laurent
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Arsac
authors.forename: Christian
authors.initials: C
authors.lastname: Ducrot
authors.forename: Carole
authors.initials: C
authors.lastname: Moreno
mesh_terms: D000483:Alleles; D000818:Animals; D001947:Breeding; D003062:Codon; D005787:Gene Frequency; D005838:Genotype; D016015:Logistic Models; D015995:Prevalence; D012044:Regression Analysis; D012307:Risk Factors; D012608:Scrapie / Q000453:epidemiology / Q000235:genetics*; D012756:Sheep / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon