Mapping of quantitative trait loci affecting classical scrapie incubation time in a population comprising several generations of scrapie-infected sheep
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.
Andréoletti, O., Berthon, P., Marc, D., Sarradin, P., Grosclaude, J., van Keulen, L., Schelcher, F., Elsen, J. M. & Lantier, F.(2000). Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol81, 3115–3126.
[Google Scholar]
Andréoletti, O., Berthon, P., Levavasseur, E., Marc, D., Lantier, F., Monks, E., Elsen, J. M. & Schelcher, F.(2002a). Phenotyping of protein-prion (PrPsc)-accumulating cells in lymphoid and neural tissues of naturally scrapie-affected sheep by double-labeling immunohistochemistry. J Histochem Cytochem50, 1357–1370.[CrossRef][Google Scholar]
Andréoletti, O., Lacroux, C., Chabert, A., Monnereau, L., Tabouret, G., Lantier, F., Berthon, P., Eychenne, F., Lafond-Benestad, S. & other authors(2002b). PrPSc accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. J Gen Virol83, 2607–2616.
[Google Scholar]
Carrell, R. W. & Gooptu, B.(1998). Conformational changes and disease – serpins, prions and Alzheimer’s. Curr Opin Struct Biol8, 799–809.[CrossRef][Google Scholar]
Ciesielski-Treska, J., Ulrich, G., Taupenot, L., Chasserot-Golaz, S., Corti, A., Aunis, D. & Bader, M. F.(1998). Chromogranin A induces a neurotoxic phenotype in brain microglial cells. J Biol Chem273, 14339–14346.[CrossRef][Google Scholar]
Diaz, C., Vitezica, Z. G., Rupp, R., Andréoletti, O. & Elsen, J. M.(2005). Polygenic variation and transmission factors involved in the resistance/susceptibility to scrapie in a Romanov flock. J Gen Virol86, 849–857.[CrossRef][Google Scholar]
Elsen, J. M., Amigues, Y., Schelcher, F., Ducrocq, V., Andreoletti, O., Eychenne, F., Khang, J. V., Poivey, J. P., Lantier, F. & Laplanche, J. L.(1999). Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol144, 431–445.[CrossRef][Google Scholar]
Evans, C. G., Wisen, S. & Gestwicki, J. E.(2006). Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1–42) aggregation in vitro. J Biol Chem281, 33182–33191.[CrossRef][Google Scholar]
Faller, E. M. & Brown, D. L.(2009). Modulation of microtubule dynamics by the microtubule-associated protein 1a. J Neurosci Res87, 1080–1089.[CrossRef][Google Scholar]
Fraser, H., Bruce, M. & McConnell, I.(1991). Murine scrapie strains, BSE models and genetics. In Sub-Acute Spongiform Encephalopathies, pp. 131–136. Edited by R. Bradley, M. Savey & B. Marchant: Commission of European Communities. The Netherlands: Kluwer Academic.
George, A. W., Visscher, P. M. & Haley, C. S.(2000). Mapping quantitative trait loci in complex pedigrees: a two-step variance component approach. Genetics156, 2081–2092.
[Google Scholar]
Gilmour, A., Gogel, B., Cullis, B., Welham, S. & Thompson, R.(2002).ASReml User Guide Release 1.0, p. 267. Hemel Hempstead, UK: VSN International Ltd.
Goldmann, W., Hunter, N., Foster, J. D., Salbaum, J. M., Beyreuther, K. & Hope, J.(1990). Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci U S A87, 2476–2480.[CrossRef][Google Scholar]
Goldmann, W., Hunter, N., Smith, G., Foster, J. & Hope, J.(1994). PrP genotypes and the Sip gene in Cheviot sheep form the basis for scrapie strain typing in sheep. Ann N Y Acad Sci724, 296–299.[CrossRef][Google Scholar]
Gooptu, B. & Lomas, D. A.(2009). Conformational pathology of the serpins: themes, variations, and therapeutic strategies. Annu Rev Biochem78, 147–176.[CrossRef][Google Scholar]
Hernandez-Sanchez, J., Waddington, D., Wiener, P., Haley, C. S. & Williams, J. L.(2002). Genome-wide search for markers associated with bovine spongiform encephalopathy. Mamm Genome13, 164–168.[CrossRef][Google Scholar]
Hooper, C. & Pocock, J. M.(2007). Chromogranin A activates diverse pathways mediating inducible nitric oxide expression and apoptosis in primary microglia. Neurosci Lett413, 227–232.[CrossRef][Google Scholar]
Houston, E. F., Halliday, S. I., Jeffrey, M., Goldmann, W. & Hunter, N.(2002). New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental challenge with a sheep-passaged scrapie isolate (SSBP/1). J Gen Virol83, 1247–1250.
[Google Scholar]
Ihara, N., Takasuga, A., Mizoshita, K., Takeda, H., Sugimoto, M., Mizoguchi, Y., Hirano, T., Itoh, T., Watanabe, T. & Reed, K. M.(2004).A Comprehensive Genetic Map of the Cattle Genome Based on 3802 Microsatellites, pp. 1987–1998. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
Jeffrey, M. & Gonzalez, L.(2004). Pathology and pathogenesis of bovine spongiform encephalopathy and scrapie. Curr Top Microbiol Immunol284, 65–97.
[Google Scholar]
Kakimura, J., Kitamura, Y., Takata, K., Umeki, M., Suzuki, S., Shibagaki, K., Taniguchi, T., Nomura, Y., Gebicke-Haerter, P. J. & other authors(2002). Microglial activation and amyloid-β clearance induced by exogenous heat-shock proteins. FASEB J16, 601–603.
[Google Scholar]
Lander, E. S. & Botstein, D.(1989). Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics121, 185–199.
[Google Scholar]
Lauren, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W. & Strittmatter, S. M.(2009). Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature457, 1128–1132.[CrossRef][Google Scholar]
Laurent, P., Schibler, L., Vaiman, A., Laubier, J., Delcros, C., Cosseddu, G., Vaiman, D., Cribiu, E. P. & Yerle, M.(2007). A 12000-rad whole-genome radiation hybrid panel in sheep: application to the study of the ovine chromosome 18 region containing a QTL for scrapie susceptibility. Anim Genet38, 358[CrossRef][Google Scholar]
Lloyd, S. E., Onwuazor, O. N., Beck, J. A., Mallinson, G., Farrall, M., Targonski, P., Collinge, J. & Fisher, E. M.(2001). Identification of multiple quantitative trait loci linked to prion disease incubation period in mice. Proc Natl Acad Sci U S A98, 6279–6283.[CrossRef][Google Scholar]
Lloyd, S. E., Uphill, J. B., Targonski, P. V., Fisher, E. M. & Collinge, J.(2002). Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice. Neurogenetics4, 77–81.[CrossRef][Google Scholar]
Lomas, D. A. & Carrell, R. W.(2002). Serpinopathies and the conformational dementias. Nat Rev Genet3, 759–768.[CrossRef][Google Scholar]
Manolakou, K., Beaton, J., McConnell, I., Farquar, C., Manson, J., Hastie, N. D., Bruce, M. & Jackson, I. J.(2001). Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice. Proc Natl Acad Sci U S A98, 7402–7407.[CrossRef][Google Scholar]
Marcos-Carcavilla, A., Calvo, J. H., Gonzalez, C., Moazami-Goudarzi, K., Laurent, P., Bertaud, M., Hayes, H., Beattie, A. E., Serrano, C. & other authors(2008). Structural and functional analysis of the HSP90AA1 gene: distribution of polymorphisms among sheep with different responses to scrapie. Cell Stress Chaperones13, 19–29.[CrossRef][Google Scholar]
Miele, G., Seeger, H., Marino, D., Eberhard, R., Heikenwalder, M., Stoeck, K., Basagni, M., Knight, R., Green, A. & other authors(2008). Urinary alpha1-antichymotrypsin: a biomarker of prion infection. PLoS One3, e3870[CrossRef][Google Scholar]
Miller, J. A., Oldham, M. C. & Geschwind, D. H.(2008). A systems level analysis of transcriptional changes in Alzheimer's disease and normal aging. J Neurosci28, 1410–1420.[CrossRef][Google Scholar]
Moreno, C. R., Lantier, F., Lantier, I., Sarradin, P. & Elsen, J. M.(2003). Detection of new quantitative trait loci for susceptibility to transmissible spongiform encephalopathies in mice. Genetics165, 2085–2091.
[Google Scholar]
Moreno, C. R., Cosseddu, G. M., Schibler, L., Roig, A., Moazami-Goudarzi, K., Andréoletti, O., Eychenne, F., Lajous, D., Schelcher, F. & other authors(2008). Identification of new quantitative trait loci (other than the PRNP gene) modulating the scrapie incubation period in sheep. Genetics179, 723–726.[CrossRef][Google Scholar]
Palmer, M. S., Dryden, A. J., Hughes, J. T. & Collinge, J.(1991). Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature352, 340–342.[CrossRef][Google Scholar]
Pong Wong, R., George, A. W., Woolliams, J. A. & Haley, C. S.(2001). A simple and rapid method for calculating identity by descent matrices using multiple markers. Genet Sel Evol33, 453–471.[CrossRef][Google Scholar]
Sanchez, M., De Givry, S. & Schiex, T.(2008). Mendelian error detection in complex pedigrees using weighted constraint satisfaction techniques. Constraints13, 130–154.[CrossRef][Google Scholar]
SAS Institute(1990).SAS/STAT User's Guide, 4 edn. Cary, NC: SAS Institute.
Schibler, L., Roig, A., Mahe, M. F., Laurent, P., Hayes, H., Rodolphe, F. & Cribiu, E. P.(2006). High-resolution comparative mapping among man, cattle and mouse suggests a role for repeat sequences in mammalian genome evolution. BMC Genomics7, 194[CrossRef][Google Scholar]
Self, S. & Liang, K.(1987). Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under nonstandard conditions. J Am Stat Assoc82, 605–610.[CrossRef][Google Scholar]
Stephenson, D. A., Chiotti, K., Ebeling, C., Groth, D., DeArmond, S. J., Prusiner, S. B. & Carlson, G. A.(2000). Quantitative trait loci affecting prion incubation time in mice. Genomics69, 47–53.[CrossRef][Google Scholar]
van Keulen, L. J., Vromans, M. E., Dolstra, C. H., Bossers, A. & van Zijderveld, F. G.(2007). Pathogenesis of bovine spongiform encephalopathy in sheep. Arch Virol153, 445–453.
[Google Scholar]
Zhang, C., De Koning, D. J., Hernandez-Sanchez, J., Haley, C. S., Williams, J. L. & Wiener, P.(2004). Mapping of multiple quantitative trait loci affecting bovine spongiform encephalopathy. Genetics167, 1863–1872.[CrossRef][Google Scholar]
Mapping of quantitative trait loci affecting classical scrapie incubation time in a population comprising several generations of scrapie-infected sheep