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Approaches to Genetic Linkage Analysis

  • M. Dawn TeareEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 713)

Abstract

Genetic linkage analysis concerns the estimation of genetic distance between two or more genetic loci. In genetic epidemiology, it is predominantly used to identify, or map, a genetic locus that is associated with quantitative trait variation or, in the case of binary or discrete traits, modification of the risk of being affected with a disease or phenotype. Linkage analysis uses a panel of reference genetic markers to track the segregation of genomic segments within families or sets of relatives. Individuals within the families must be measured for the trait, and often the families have been selected because they segregate the phenotype of interest.

Key words

Human genetic linkage Recombination fraction Allelic segregation Model-based linkage analysis Model-free linkage analysis 

References

  1. 1.
    Morton NE. (1955) Sequential tests for the detection of linkage. Am J Hum Genet. 7:277–318.PubMedGoogle Scholar
  2. 2.
    Teare MD, Barrett JH. (2005) Genetic epidemiology 2 – Genetic linkage studies. Lancet. 366:1036–1044.CrossRefGoogle Scholar
  3. 3.
    Lander E, Kruglyak L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 11:241–247.PubMedCrossRefGoogle Scholar
  4. 4.
    Cannings C, Thompson EA. (1977) Ascertainment in the sequential sampling of pedigrees. Clin Genet. 12:208–212.PubMedCrossRefGoogle Scholar
  5. 5.
    Elston RC, Stewart J. (1971) A general model for the genetic analysis of pedigree data. Hum Hered. 21:523–542.PubMedCrossRefGoogle Scholar
  6. 6.
    Lander ES, Green P. (1987) Construction of multilocus genetic-linkage maps in humans. Proc Nat Acad Sci. 84:2363–2367.PubMedCrossRefGoogle Scholar
  7. 7.
    Markianos K, Daly MJ, Kruglyak L. (2001) Efficient multipoint linkage analysis through reduction of inheritance space. Am J Hum Genet. 68:963–977.PubMedCrossRefGoogle Scholar
  8. 8.
    Abecasis GR, Cherny SS, Cookson WO, et al. (2002) Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet. 30:97–101.PubMedCrossRefGoogle Scholar
  9. 9.
    Rapley EA, Crockford GP, Teare D, et al. (2000) Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours. Nat Genet. 24:197–200.PubMedCrossRefGoogle Scholar
  10. 10.
    Thompson EA. (2008) The IBD process along four chromosomes. Theor Pop Biol. 73:369–373.CrossRefGoogle Scholar
  11. 11.
    Risch N, Merikangas K. (1996) The future of genetic studies of complex diseases. Science. 273:1516–1517.PubMedCrossRefGoogle Scholar
  12. 12.
    Haseman JK, Elston RC. (1972) The investigation between a quantitative trait and a marker locus. Behav Genet. 2:3–19.PubMedCrossRefGoogle Scholar
  13. 13.
    Wright FA. (1997) The phenotypic difference discards sib-pair QTL linkage information. Am J Hum Genet. 60:740–742.PubMedGoogle Scholar
  14. 14.
    Drigalenko E. (1998) How sib pairs reveal linkage. Am J Hum Genet. 63:1242–1245.PubMedGoogle Scholar
  15. 15.
    Risch N, Zhang H. (1996) Mapping quantitative trait loci with extreme discordant sib pairs: Sampling considerations. Am J Hum Genet. 58:836–843.PubMedGoogle Scholar
  16. 16.
    Feingold E. (2001) Methods for linkage analysis of quantitative trait loci in humans. Theor Pop Biol. 60:167–180.CrossRefGoogle Scholar
  17. 17.
    Amos CI. (1994) Robust variance-components approach for assessing genetic linkage in pedigrees. Am J Hum Genet. 54:535–543.PubMedGoogle Scholar
  18. 18.
    Almasy L, Blangero J. (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet. 62:1198–1211.PubMedCrossRefGoogle Scholar
  19. 19.
    Clerget-Darpoux F, Elston RC. (2007) Are linkage analysis and the collection of family data dead? Prospects for family studies in the age of genome-wide association. Hum Hered. 64:91–96.PubMedCrossRefGoogle Scholar
  20. 20.
    Wise LH, Lanchbury JS, Lewis CN. (1999) Meta-analysis of genome searches. Ann Hum Genet. 63:263–272.PubMedCrossRefGoogle Scholar
  21. 21.
    Skare O, Sheehan N, Egeland T. (2009) Identification of distant family relationships. Bioinformatics. 25:2376–2382.PubMedCrossRefGoogle Scholar
  22. 22.
    Gusev A, Lowe JK, Stoffel M. (2009) Whole population, genome-wide mapping of hidden relatedness. Genome Res. 19:318–326.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Health Services Research, School of Health and Related ResearchUniversity of SheffieldSheffieldUK

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