Structural and functional analysis of the HSP90AA1 gene: distribution of polymorphisms among sheep with different responses to scrapie

Abstract

Scrapie is a transmissible spongiform encephalopathy in sheep and goats. Susceptibility to this neurodegenerative disease is mainly controlled by point mutations at the PRNP locus. Other genes, apart from PRNP, have been reported to modulate resistance/susceptibility to scrapie. On the basis of several studies in Alzheimer and different transmissible spongiform encephalopathy models, HSP90AA1 was chosen as a putative positional and functional candidate gene that might be involved in the polygenic variance mentioned above. In the present work, the ovine HSP90AA1 gene including the promoter and other regulatory regions has been isolated and characterized. Several sequence polymorphisms have also been identified. FISH-mapping localized the HSP90AA1 gene on ovine chromosome OAR19q24dist, which was confirmed by linkage analysis. This chromosome region has been shown to include a quantitative trait loci (QTL) for scrapie incubation period in sheep. Expression analyses were carried out in spleen and cerebellum samples. No differences in the expression of the HSP90AA1 gene were found in any of these tissues (p>0.05) between control and infected animal samples. Nevertheless, association analyses revealed that several polymorphisms in the 5′ and 3′ regions of the HSP90AA1 gene were differentially distributed among animals with different responses to scrapie infection. Thus, results presented here support the hypothesis that HSP90AA1 could be a positional and functional candidate gene modulating the response to scrapie in sheep.

Polymorphisms at the 5′ flanking region of the HSP90AA1 gene in native Turkish sheep breeds

“…Under stress conditions (heat shock, missfolding, etc. ), animals carrying the CC genotype of this mutation have higher expression rates than those with the CG or GG genotype (Marcos-Carcavilla et al, 2008, 2010a.…”

“…Recent changes in animal production systems and climatic conditions have led to research characterizing genes related to animal's adaptation to the environment (Adamowicz et al, 2005;Marcos-Carcavilla et al, 2008;Schwerin et al, 2002). Heat stress is considered a limiting factor for sheep production (McManus et al, 2009).…”

“…The ovine gene encoding the inducible form (HSP90AA1) has been characterized recently (Marcos-Carcavilla et al, 2008) which found several SNPs located in the 5 0 flanking region associated with the response to scrapie and the adaptive response to heat stress. It was hypothesized that a C-G transversion at the À 660 position in the 5 0 flanking region is related to the expression level of the HSP90AA1 gene.…”

Biomarcadores asociados con scrapie y otras encefalopatías espongiformes transmisibles

“…Además de los estudios de expresión, debido a su localización en una región QTL, se propuso el gen HSP90AA1 como candidato a modular la susceptibilidad a scrapie (Marcos-Carcavilla et al, 2008a). Posteriormente se determinó que ciertos polimorfismos de este gen podrían explicar las diferencias en el periodo de incubación de scrapie observadas entre individuos con igual genotipo para el gen PRNP (Marcos-Carcavilla et al, 2010).…”

Analysis of 3’UTR of Prnp Gene in Mammals: Possible Role of Target Sequences of miRNA for TSE Sensitivity in Bovidae and Cervidae

“…Otherwise, several studies point out that the expression level of the prion gene could modulate the onset of TSE, particularly in cattle (Sander et al, 2004(Sander et al, -2006Haase et al, 2007). The involvement of the 5' promoter region has been investigated in sheep (Saunders et al, 2009) and cattle (Xue et al, 2008) and it appears that polymorphism in this region could induce different responses to scrapie (Marcos-Carcavilla et al, 2008) and BSE (Brunelle et al, 2008). The analysis of a 23 pb insertion/deletion polymorphism in German and Swiss breed cattle revealed that the deletion is associated to a higher expression level, more frequently A Bird's-Eye View of Veterinary Medicine 524 found in cattle affected with classical BSE.…”