Analysis of Genetic Linkage Data for Mendelian Traits

Nicole D. Dueker1, Margaret A. Pericak‐Vance1

1 University of Miami Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, Florida
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 1.4
DOI:  10.1002/0471142905.hg0104s83
Online Posting Date:  October, 2014
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This unit describes linkage analysis, an invaluable tool in mapping human disease genes. Linkage analysis is one of several methods used to map genes. Specifically, in linkage analysis, cosegregation of two or more genes (traits) is examined in a family unit to determine if they segregate independently of each other according to Mendel's laws or if they do not segregate independently because of their close physical proximity. The procedures outlined in this unit are not always straightforward, and a number of caveats are presented in the commentary regarding possible complications and confounding factors that may arise. Specific examples are given, but it is not possible to cover all possible scenarios or variables. The intention is to enable the reader to master basic principles used in the linkage approach, and thus be in a position to undertake, with proper consultation, a linkage‐analysis study. This unit deals specifically with lod score analysis in Mendelian disorders. Curr. Protoc. Hum. Genet. 83:1.4.1‐1.4.31. © 2014 by John Wiley & Sons, Inc.

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Table of Contents

  • Introduction
  • Key Concepts
  • Strategic Approach
  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

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  Xing, C., Morris, N., and Xing, G. 2010. Distribution of model‐based multipoint heterogeneity lod scores. Genet. Epidemiol. 34:912‐916.
  Yamaoka, L.H., Westbrook, C.A., Speer, M.C., Gilchrist, J.M., Jabs, E.W., Stajich, J.M., Gaskell, C.P., Roses, A.D., and Pericak‐Vance, M.A. 1993. Autosomal dominant muscular dystrophy (LGM1): A genetic map of chromosome 5q31 and refining the location of LGM1 by multipoint analysis. Am. J. Hum. Genet. 53:A1110.
Key References
  Conneally and Rivas, 1980. See above.
  Summarizes linkage analysis up to 1980; good historical background.
  Devlin and Risch, 1995. See above.
  Compares various linkage disequilibrium measures for high‐resolution mapping.
  Elston and Stewart, 1971. See above.
  Original paper describing the Elston‐Stewart algorithm for pedigree analysis.
  Elston, R.C. and Johnson, W.D. 1987. Essentials of Biostatistics. F.A. Davis, Philadelphia, Pennsylvania.
  Good practical introductory biostatistics book for nonstatisticians.
  Lathrop et al., 1984. See above.
  Classical paper on multipoint linkage analysis.
  Morton, 1955. See above.
  Classical paper describing the lod‐score approach to linkage.
  O'Connell and Weeks, 1995. See above.
  Describes VITESSE, an algorithm for rapid and efficient multipoint analysis.
  Ott, 1992. See above.
  Outstanding resource book considering theoretical as well as practical aspects of linkage analysis.
  Weir, B.S. 1990. Genetic Data Analysis. Sinauer Associates, Sunderland, Massachusetts.
  Theoretical guide to linkage disequilibrium.
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