Mapping of quantitative trait loci affecting classical scrapie incubation time in a population comprising several generations of scrapie-infected sheep

Abstract

Although susceptibility to scrapie is largely controlled by the PrP gene, the role of other genes that affect scrapie resistance in sheep is now confirmed. Following the detection of quantitative trait loci (QTL) on chromosomes 6 and 18 in a half-sib family with an ARQ/VRQ susceptible PrP genotype, the whole pedigree of a naturally infected flock was investigated to confirm these QTL regions in different PrP genotypes. The present study has allowed us to confirm the QTL on chromosome 18, and to demonstrate the QTL effects in several PrP genotypes. INTRODUCTIONScrapie is a transmissible spongiform encephalopathy (TSE), and host resistance is largely controlled by the PrP gene encoding the PrP protein (Goldmann et al., 1990;Palmer et al., 1991). Recently, some loci that modulate susceptibility to TSEs, other than the PrP gene, have been detected in mice (Lloyd et al., 2001(Lloyd et al., , 2002Manolakou et al., 2001;Moreno et al., 2003;Stephenson et al., 2000) and cattle (HernandezSanchez et al., 2002; Zhang et al., 2004). In sheep, Diaz et al. (2005) have shown that the PrP gene explains only part of the total genetic variance of the survival time in a Romanov sheep flock naturally infected by scrapie. Moreno et al. (2008) detected two quantitative trait loci (QTL) regions (at the 5 % chromosome-wide level) affecting scrapie incubation time, on chromosomes 6 and 18, in one half-sib family of 67 scrapie-affected animals.In this article, our aim was to confirm QTL previously detected by Moreno et al. (2008) by using additional data from the sheep population from the INRA Langlade farm and to verify their presence in the PrP genotypes with different scrapie susceptibilities. RESULTSThe significant fixed effects affecting incubation time were the PrP genotype (P,0.001), rearing (P,0.006), litter size (P,0.01), the PrP genotype of dam (P,0.05) and the interaction between season and birth year (P,0.001). The significance of the PrP genotype is mainly due to the greater estimated mean of incubation time for the ARQ/ VRQ genotype compared with the other genotypes (Table 1). However, the standard deviation of the ARQ/ VRQ population was similar to that of the ARQ/ARQ population, but twice that of the VRQ/VRQ population. Because heterogeneous variances were observed between VRQ/VRQ and ARQ/---sub-populations, the variance component analyses were repeated for these two genotype groups separately.The heritabilities of scrapie incubation time estimated in the total population and in sub-populations are shown in Table 2. These heritabilities suggest that, in addition to the PrP effects, a proportion of the between-animal variability is due to genetic effects. However, the estimated values were somewhat (albeit not significantly, P.0.05) higher in the two sub-populations than in the total dataset, particularly when the QTL effect was not fitted.The data provided no evidence of a QTL on chromosome 6, with the likelihood ratio test (LRT) value being close to zero at all tested locations. However, a significant QTL was identified o...

Discovering novel clues of natural selection on four worldwide goat breeds

“…It is worth noting that this gene maps inside a QTL region identified in sheep and involved in scrapie infection, a disease of the nervous system 33 . In the same genomic region of CH21, we also found MAP1A, that allows the maintenance and restructuring of adult neurons 34 and maps inside a QTL affecting classical scrapie incubation time in a population of scrapie-infected 35 .…”

Biomarcadores asociados con scrapie y otras encefalopatías espongiformes transmisibles

“…Los estudios destinados a la identificación de marcadores génicos que permitan explicar las diferencias individuales en cuanto a susceptibilidad o periodo de incubación de estas enfermedades se han realizado tanto en modelos murinos de EETs (Moreno et al, 2003) co mo en las especies que padecen estas patologías de forma natural, la especie humana (Mead et al, 2009), ovina (Moreno et al, 2010), bovina (Murdoch et al, 2011) o cérvidos (Matsumoto et al, 2013). Estos estudios han determinado genes candidatos implicados en procesos que podrían desempeñar un papel importante en la patología y la patogenia de estas enfermedades.…”

Biomarcadores asociados con scrapie y otras encefalopatías espongiformes transmisibles

“…Los estudios destinados a la identificación de marcadores génicos que permitan explicar las diferencias individuales en cuanto a susceptibilidad o periodo de incubación de estas enfermedades se han realizado tanto en modelos murinos de EETs (Moreno et al, 2003) co mo en las especies que padecen estas patologías de forma natural, la especie humana (Mead et al, 2009), ovina (Moreno et al, 2010), bovina (Murdoch et al, 2011) o cérvidos (Matsumoto et al, 2013). Estos estudios han determinado genes candidatos implicados en procesos que podrían desempeñar un papel importante en la patología y la patogenia de estas enfermedades.…”