Using genotype probabilities in survival analysis: a scrapie case

Abstract

-The objective was to evaluate the potential use of genotype probabilities to handle records of non-genotyped animals in the context of survival analysis. To do so, the risks associated with the PrP genotype and other transmission factors in relation to clinical scrapie were estimated. Data from 4049 Romanov sheep affected by natural scrapie were analyzed using survival analysis techniques. The original data set included 1310 animals with missing genotypes; five of those had uncensored records. Different missing genotype-information patterns were simulated for uncensored and censored records. Three strategies differing in the way genotype information was handled were tested. Firstly, records with unknown genotypes were discarded (P1); secondly, those records were grouped in an unknown class (P2). Finally the probabilities of genotypes were assigned (P3). Whatever the strategy, the ranking of relative risks for the most susceptible genotypes (VRQ-VRQ, ARQ-VRQ and ARQ-ARQ) was similar even when the non-genotyped animals were not a negligible part of uncensored records. However, P3 had a more efficient way of handling missing genotype information. As compared to P1, either P2 or P3 avoided discarding the records of non-genotyped animals; however, P3 eliminated the unknown class and the risk associated with this group. Genotype probabilities were shown to be a useful technique to handle records of individuals with unknown genotype.genotype probabilities / survival analysis / PrP genotypes / scrapie

Polygenic variation and transmission factors involved in the resistance/susceptibility to scrapie in a Romanov flock

“…Ten PrP genotypes were considered. In total, 1310 individuals did not have a known genotype; however, they were kept in the dataset to obtain a better estimate of other risk factors in the models (Vitezica et al, 2005). To deal with nongenotyped individuals, we proceeded in two ways.…”

“…However, to estimate polygenic variance, probabilities of genotypes were used, because they were expected to provide additional information (Meuwissen & Goddard, 1997). For instance, these probabilities recognized the heterogeneity of genotypes of the non-genotyped group (Vitezica et al, 2005).Litter size (Ls). This factor represents the size of the litter in which the animal was born.…”

Ultrasensitive detection of scrapie prion protein derived from ARQ and AHQ homozygote sheep by interspecies in vitro amplification

“…There are five commonly occurring alleles: V 136 R 154 Q 171 , ARQ , ARR , AHQ and ARH . ARR / ARR sheep seemed to be highly resistant to scrapie infection, whereas VRQ / VRQ sheep have been found to be most susceptible (9–12). In addition to classical scrapie, atypical scrapie has been reported in recent years (13–15).…”

Epidemiological and genetical differences between classical and atypical scrapie cases

“…Consequently, current regulations of the European Union aim to eradicate ovine scrapie from the member states by selecting for the PrP haplotype A 136 R 154 R 171 (ARR), regarded to be most resistant to scrapie, and to eliminate the other haplotypes, mainly VRQ, which is suspected to be most susceptible (e.g. [1,8,14,37]). This is imple- In recent years, "atypical" scrapie cases have been identified [3,7].…”