Skip to main content
SpringerLink
Log in
Book cover

Celiac Disease pp 33–54Cite as

Linkage and the Transmission Disequilibrium Test in Complex Traits

Celiac Disease as a Case Study

  • Protocol

  • 640 Accesses

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 41))

Abstract

Many disorders such as celiac disease do not conform to a simple Mendelian model of inheritance and display a complex pattern of inheritance indicative of the interaction of a number of distinct susceptibility genes. Susceptibility to celiac disease is genetically determined by possession of specific HLA DQ alleles, acting in concert with one or more non-HLA-linked genes. Haplotypesharing probabilities across the HLA region in affected sibling pairs suggest that genes within the major histocompatibility complex (MHC) contribute no more than 30% of the sibling familial risk of celiac disease, making the non-HLA-linked gene (or genes) the stronger determinant of celiac disease susceptibility (1). Locating these non-HLA-linked genes can be undertaken by either linkage or association. The relative merits of these two approaches depend critically on the frequency and genotypic risks associated with susceptibility genes.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Houlston, R. S. and Ford, D. (1996) Genetics of coeliac disease. QJM 89, 737–743.

    Article  PubMed  CAS  Google Scholar 

  2. Risch, N. (1990) Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am. J. Hum. Genet. 46, 229–241.

    PubMed  CAS  Google Scholar 

  3. Holmans, P. (1993) Asyptoric properties of affected-sib-pair analysis. Am. J. Hum. Genet. 52(2), 362–374.

    PubMed  CAS  Google Scholar 

  4. Holmans, P. (1993) Asyptoric properties of affected-sib-pair linkage analysis. Am. J. Hum. Genet. 52, 362–374.

    PubMed  CAS  Google Scholar 

  5. Kruglyak, L. and Lander, E. S. (1995) Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am. J. Hum. Genet. 57, 439–454.

    PubMed  CAS  Google Scholar 

  6. Kruglyak, L., Daly, M. J., Reeve-Daly, M. P., and Lander, E. S. (1996) Parametric and nonparametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363.

    PubMed  CAS  Google Scholar 

  7. Lander, E. and Kruglyak, L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat. Genet. 11, 241–247.

    Article  PubMed  CAS  Google Scholar 

  8. Hodge, S. E. (1984) The information contained in multiple sibling pairs. Genet. Epidemiol. 1, 109–122.

    Article  PubMed  CAS  Google Scholar 

  9. Risch, N. (1990) Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am. J. Hum. Genet. 46, 242–253.

    PubMed  CAS  Google Scholar 

  10. Weeks, D. E., Ott, J., and Lathrop, G. M. (1989) SLINK: a general simulation program for linkage analysis. Am. J. Hum. Genet. 47, A204.

    Google Scholar 

  11. Spielman, R. S. and Ewens, W. J. (1996) The TDT and other family-based tests for linkage disequilibrium and association. Am. J. Hum. Genet. 59, 983–989.

    PubMed  CAS  Google Scholar 

  12. Ploughman, L. M. and Boehnke, M. (1989) Estimating the power of a proposed linkage study for a complex trait. Am. J. Hum. Genet. 44, 543–551.

    PubMed  CAS  Google Scholar 

  13. Terwilliger, J. D. (1995) A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. Am. J. Hum. Genet. 56, 777–787.

    PubMed  CAS  Google Scholar 

  14. Morris, A. P., Curnow, R. N., and Whittaker, J. C. (1997) Randomisation tests of disease-marker associations. Ann. Hum. Genet. 61, 49–60.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Risch, N. and Merikangas, K. (1996) The future of genetic studies of complex human disease. Science 273, 1516, 1517.

    Article  PubMed  CAS  Google Scholar 

  17. Curtis, D. and Sham, P. C. (1995) A note on the application of the transmission disequilibrium test when a parent is missing. Am. J. Hum. Genet. 56, 811, 812.

    PubMed  CAS  Google Scholar 

  18. Camp, N. J. (1997) Genomewide transmission/disequilibrium testing—consideration of the genotypic relative risks at disease loci. Am. J. Hum. Genet. 61, 1424–1430.

    Article  PubMed  CAS  Google Scholar 

  19. Bevan, S., Popat, S., Ferguson, A., et al. Contribution of the MHC region to the familial risk of coeliac disease. J. Med. Genet. 36(9), 687–690.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cancer Research, Sutton, Surrey, UK

    Stephen Bevan

  2. Haddow Laboratory, Institute of Cancer Research, Sutton, Surrey, UK

    Richard S. Houlston

Authors
  1. Stephen Bevan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard S. Houlston
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Manchester, Salford, UK

    Michael N. Marsh MD, DSc, FRCP

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Bevan, S., Houlston, R.S. (2000). Linkage and the Transmission Disequilibrium Test in Complex Traits. In: Marsh, M.N. (eds) Celiac Disease. Methods in Molecular Medicine, vol 41. Humana Press. https://doi.org/10.1385/1-59259-082-9:033

Download citation

  • DOI: https://doi.org/10.1385/1-59259-082-9:033

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-650-5

  • Online ISBN: 978-1-59259-082-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation