Skip to main content
Log in

Genome-wide search for markers associated with bovine spongiform encephalopathy

  • Short Communications
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

A genome-wide search for markers associated with BSE incidence was performed by using Transmission-Disequilibrium Tests (TDTs). Significant segregation distortion, i.e., unequal transmission probabilities of alleles within a locus, was found for three marker loci on Chromosomes (Chrs) 5, 10, and 20. Although TDTs are robust to false associations owing to hidden population substructures, it cannot distinguish segregation distortion caused by a true association between a marker and bovine spongiform encephalopathy (BSE) from a population-wide distortion. An interaction test and a segregation distortion analysis in half-sib controls were used to disentangle these two alternative hypotheses. None of the markers showed any significant interaction between allele transmission rates and disease status, and only the marker on Chr 10 showed a significant segregation distortion in control individuals. Nevertheless, the control group may have been a mixture of resistant and susceptible but unchallenged individuals. When new genotypes were generated in the vicinity of these three markers, evidence for an association with BSE was confirmed for the locus on Chr 5.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Almond G, Pattison J (1997) Human BSE. Nature 389, 437–438

    Article  PubMed  CAS  Google Scholar 

  • Ando S, Sirianni R, Forastieri P, Casaburi I, Lanzino M et al. (2001) Aromatase expression in prepuberal Sertoli cells: effect of thyroid hormone. Mol Cell Endocrinol 178, 11–21

    Article  PubMed  CAS  Google Scholar 

  • Arranz JJ, Coppieters W, Berzi P, Cambisano N, Grisart B, et al. (1998) A QTL affecting milk yield and composition maps to bovine Chromosome 20: a confirmation. Anim Genet 29, 107–115

    Article  PubMed  CAS  Google Scholar 

  • Bach G, Tomczak J, Risch N, Ekstein J (2001) Tay-Sachs screening in the Jewish Ashkenazi population: DNA testing is preferred procedure. Am J Med Genet 99, 70–75

    Article  PubMed  CAS  Google Scholar 

  • Bickeböller H, Clerget-Darpoux F (1995) Statistical properties of the allelic and genotypic transmission/disequilibrium test for multiallelic markers. Genet Epidemiol 12, 865–870

    Article  PubMed  Google Scholar 

  • Bradley DG, Cunningham EP (1999) Genetic aspects of domestication. InThe Genetics of Cattle, R Fries, A Ruvinsky, eds. (Wallingford: CAB International) pp 15–31

    Google Scholar 

  • Bruce M, Chree A, McConnell I, Foster J, Pearson G et al. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philos Trans R Soc Lond B, Biol Sci 343, 405–411

    Article  CAS  Google Scholar 

  • Bruce ME, Will RG, Ironside JW, McConnel I, Drummond D et al. (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389, 488–501

    Article  CAS  Google Scholar 

  • (The) BSE enquiry: www.bseinquiry.gov.uk/index.htm

  • Carreau S (2001) Germ cells: a new source of estrogens in the male gonad. Mol Cell Endocrinol 178, 65–72

    Article  PubMed  CAS  Google Scholar 

  • Chakravarti A (1998) It’s raining SNPs, hallelujah? Nat Genet 19, 216–217

    Article  PubMed  CAS  Google Scholar 

  • Cox DR (1970)Analysis of Binary Data. (London: Methuen & Co. Ltd.)

    Google Scholar 

  • Curtis D, Sham PC (1985) A note on the application of the transmission-disequilibrium test when a parent is missing. Am J Hum Genet 56, 811–812

    Google Scholar 

  • Donnelly CA, Ferguson NM, Ghani AC, Wilesmith JW, Anderson RM (1997) Analysis of dam-calf pairs of BSE cases: confirmation of a maternal risk enhancement. Proc R Soc Lond B, 264, 1647–1656

    Article  CAS  Google Scholar 

  • Ewens WJ, Spielman RS (1995) The transmission/disequilibrium test: history, subdivision and admixture. Am J Hum Genet 57, 455–464

    PubMed  CAS  Google Scholar 

  • Farnir F, Coppieters W, Arranz JJ, Berzi P, Cambrisano N, et al. (2000) Extensive genome-wide linkage disequilibrium in cattle. Genome Res 10, 220–227

    Article  PubMed  CAS  Google Scholar 

  • Ferguson NM, Donnelly CA, Woolhouse MEJ, Anderson RM (1997) A genetic interpretation of heightened risk of BSE in offspring of affected dams. Proc R Soc Lond B 24, 1445–1455

    Article  Google Scholar 

  • Genissel C, Carreau S (2001) Regulation of the aromatase gene expression in mature Leydig cells. Mol Cell Endocrinol 178, 141–146

    Article  PubMed  CAS  Google Scholar 

  • Goldmann W, Hunter N, Foster JD, Salbaum JM, Beyreuther K et al. (1990) Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci USA 87, 2476–2480

    Article  PubMed  CAS  Google Scholar 

  • Goldmann W, Hunter N, Martin T, Dawson M, Hope J (1991) Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein coding exon. J Gen Virol 72, 201–204

    PubMed  CAS  Google Scholar 

  • Goldmann W, Hunter N, Smith G, Foster J, Hope J (1994) PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 75, 989–995

    PubMed  CAS  Google Scholar 

  • Goldmann W, Martin T, Foster J, Hughes S, Smith G et al. (1996) Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period. J Gen Virol 77, 2885–2891

    Article  PubMed  CAS  Google Scholar 

  • Goldstein DB (2001) Islands of linkage disequilibrium. Nat Genet 29, 109–111

    Article  PubMed  CAS  Google Scholar 

  • Hunter N (1999) Molecular biology and genetics of bovine spongiform encephalopathy. InThe Genetics of Cattle R Fries, A Ruvinsky, eds. (Wallingford: CAB International), pp 229–246

    Google Scholar 

  • Hunter N, Goldmann W, Smith G, Hope J (1994) Frequencies of PrP gene variants in healthy cattle and cattle with BSE in Scotland. Vet Rec 135, 400–403

    PubMed  CAS  Google Scholar 

  • Johnson GCL, Esposito L, Barratt BJ, Smith AN, Heward J, et al. (2001) Haplotype tagging for the identification of common disease genes. Nat Genet 29, 233–237

    Article  PubMed  CAS  Google Scholar 

  • Kruglyak L (1999) Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet 22, 139–144

    Article  PubMed  CAS  Google Scholar 

  • Kuerer HM, Buzdar AU, Singletary SE (2001) Biologic basis and evolving role of aromatase inhibitors in the management of invasive carcinoma of the breast. J Surg Oncol 77, 139–147

    Article  PubMed  CAS  Google Scholar 

  • Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265, 2037–2048

    Article  PubMed  CAS  Google Scholar 

  • Leach DRF (1996)Genetic Recombination (Oxford: Blackwell Science Ltd)

    Google Scholar 

  • Lloyd SE, Onwuazor ON, Beck JA, Mallinson G, Farrall M et al. (2001) Identification of multiple quantitative trait loci linked to prion disease incubation period in mice. Proc Nat Acad Sci USA 98, 6279–6283

    Article  PubMed  CAS  Google Scholar 

  • Manolakou K, Beaton J, McConnell I, Farquar C, Manson J et al. (2001) Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice. Proc Nat Acad Sci USA 98, 7402–7407

    Article  PubMed  CAS  Google Scholar 

  • McCullagh P, Neider JA (1983) Generalised linear models: monographs on statistics and applied probability, 1st and 2nd edns. (London: Chapman and Hall)

    Google Scholar 

  • Mouse Genome Database (MGD), Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine,(http://www.informatics.jax.org).

  • Neibergs HL, Ryan AM, Womack JE, Spooner RL, Williams JL (1994) Polymorphism analysis of the prion gene in BSE-affected and unaffected cattle. Anim Genet 25, 313–317

    Article  PubMed  CAS  Google Scholar 

  • Ott J (2000) Predicting the range of linkage disequilibrium. Proc Natl Acad Sci USA 97, 2–3

    Article  PubMed  CAS  Google Scholar 

  • Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfelt-Jakob disease. Nature 352, 340–342

    Article  PubMed  CAS  Google Scholar 

  • Riquet J, Coppieters W, Cambrisano N, Arranz JJ, Berzi P, et al. (1999) Fine-mapping of quantitative trait loci by identity by descent in outbred populations: application to milk production in dairy cattle. Proc Natl Acad Sci USA 96, 9252–9257

    Article  PubMed  CAS  Google Scholar 

  • Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273, 1516–1517

    Article  PubMed  CAS  Google Scholar 

  • Roughsedge T, Brotherstone S, Visscher PM (1999) Quantifying genetic contributions to a dairy cattle population using pedigree analysis. Livest Prod Sci 60, 359–369

    Article  Google Scholar 

  • Ryan AM, Womack JE (1993) Somatic cell mapping of the bovine prion protein gene and restriction fragment length polymorphism studies in cattle and sheep. Anim Genet 24, 23–26

    Article  PubMed  CAS  Google Scholar 

  • Schork NJ, Fallin D, Thiel B, Xu X, Broeckel U et al. (2001) The future of genetic case-control studies. InGenetic Dissection of Complex Traits, Rao DC, Province MA, eds. (San Diego: Academic Press), pp 191–212

    Google Scholar 

  • Sham PC, Curtis D (1995) An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Ann Hum Genet 59, 323–336

    PubMed  CAS  Google Scholar 

  • Sham PC, Zhao JH, Waldman I, Curtis D (2000) Should ambiguous trios for the TDT be discarded? Ann Hum Genet 64, 575–576

    Article  PubMed  CAS  Google Scholar 

  • Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52, 506–516

    PubMed  CAS  Google Scholar 

  • Stephenson DA, Chiotti K, Ebeling C, Groth D, DeArmond SJ et al. (2000) Quantitative trait loci affecting prion incubation time in mice. Genomics 69, 47–53

    Article  PubMed  CAS  Google Scholar 

  • Terwilliger J, Ott J (1992) A haplotype-based ‘haplotype relative risk’ approach to detecting allelic associations. Hum Hered 42, 337–346

    Article  PubMed  CAS  Google Scholar 

  • Terwilliger JD, Weiss KM (1998) Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol 9, 578–594

    Article  PubMed  CAS  Google Scholar 

  • Waldman ID, Robinson BF, Rowe DC (1999) A logistic regression based extension of the TDT for continuous and categorical traits. Ann Hum Genet 63, 329–340

    Article  PubMed  CAS  Google Scholar 

  • Warren JE, Spielman RS (1995) The Transmission/Disequilibrium test: history, subdivision and admixture. Am J Hum Genet 57, 455–464

    Google Scholar 

  • Wickman S, Sipila I, Ankarberg-Lindgren C, Norjavaara E, Dunkel L (2001) A specifc aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomized controlled trial. Lancet 357, 1723–1724

    Article  Google Scholar 

  • Young GB, Lee GJ, Waddington D, Sales DI, Bradley JS et al. (1983) Culling and wastage in dairy cows in East Anglia. Vet Rec 113, 107–111

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Subscribers can view a supplementary table for this article at url:http:// link.springer-ny/link/service/journals/OO335/contents/01/3068/paper/ index.html.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hernández-Sánchez, J., Waddington, D., Wiener, P. et al. Genome-wide search for markers associated with bovine spongiform encephalopathy. Mammalian Genome 13, 164–168 (2002). https://doi.org/10.1007/BF02684022

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02684022

Keywords

Navigation