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

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Cell Stress and Chaperones Aims and scope

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.

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Acknowledgment

We thank the CERSYRA-Valdepeñas and AGRAMA breeders association, CSIC-León, CITA-Aragón, Prion Research Centre of the University of Zaragoza—and INIA-Madrid for kindly providing Manchega, Awassi, Assaf, Rasa Aragonesa and Mouflon samples. We are very grateful to Dr. K.G. Dodds for his suggestions and English correction of the manuscript, to Dr. MA Roca for helping us with the PCRs improvement, to Dr. C.R. Moreno for her suggestions in the statistical area, to Dr. M.E.F. Alves for her continuous help and to Dr. E.P. Cribiu and Dr. P. Zaragoza for allowing us to perform the cytogenetic mapping and the expression analysis in their respective laboratories. This work was supported by the RTA2006–00104 INIA project, and a Predoctoral Grant from the INIA.

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Authors and Affiliations

  1. Departamento de Mejora Genética Animal, INIA, Ctra La Coruña Km 7.5, 28040, Madrid, Spain

    Ane Marcos-Carcavilla, Carmen González & Magdalena Serrano

  2. Unidad de Tecnología en Producción Animal, Avda. Montañana 930, CITA, 50059, Zaragoza, Spain

    Jorge H. Calvo

  3. Laboratoire de Génétique biochimique et de Cytogénétique, Département de Génétique Animale, INRA, Centre de Recherche de Jouy, 78352, Jouy-en-Josas, Cedex, France

    Katayoun Moazami-Goudarzi, Pascal Laurent, Maud Bertaud & Hélène Hayes

  4. AgResearch, Invermay Agricultural Centre, Private Bag, 50034, Mosgiel, New Zealand

    Anne E. Beattie

  5. Laboratorio de Genética Bioquímica, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain

    Carmen Serrano, Jaber Lyahyai & Inmaculada Martín-Burriel

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  1. Ane Marcos-Carcavilla
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  2. Jorge H. Calvo
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Correspondence to Ane Marcos-Carcavilla.

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Marcos-Carcavilla, A., Calvo, J.H., González, C. et al. Structural and functional analysis of the HSP90AA1 gene: distribution of polymorphisms among sheep with different responses to scrapie. Cell Stress and Chaperones 13, 19–29 (2008). https://doi.org/10.1007/s12192-007-0004-2

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  • DOI: https://doi.org/10.1007/s12192-007-0004-2

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