AN INTRODUCTION TO GENETIC ASSOCIATION AND LINKAGE ANALYSIS

David Duffy (davidD@qimr.edu.au)

Overview

  1. Review of classical genetics
    1. Mendelism
    2. Linkage
  2. Basic statistical procedures in classical genetics
    1. Goodness-of-fit testing of distributions of counts
    2. The binomial distribution
    3. The Pearson chi-square
    4. Segregation ratios
    5. Linkage in experimental crosses
  3. Review of elementary population genetics
    1. Hardy-Weinberg equilibrium
    2. Linkage equilibrium
    3. Mutation
  4. Genetic association studies
    1. Case-control designs
    2. Family based designs
    3. Haplotype Relative Risk
    4. Transmission Disequilibrium Test
    5. Tests of cosegregation of trait and marker
  5. Simple and nonparametric linkage analysis
    1. Counting methods (as in testcross situation)
    2. Sib-pair methods
    3. Affected sib-pair analysis
    4. Haseman-Elston methods
    5. Affected pedigree member methods
    6. APM
    7. SIMIBD
    8. Genehunter
  6. Parametric (LOD score) linkage analysis
    1. Likelihood
    2. What is likelihood
    3. Likelihood for linkage
    4. Some examples
  7. MLINK and two-point LOD score linkage analysis
    1. Preparing data for analysis
    2. MAKEPED and PREPLINK
    3. Running MLINK
    4. Autosomal mendelian traits
    5. Sex-linked recessives
    6. Loops and LOOPS
    7. Age-dependent penetrance
  8. CRI-MAP and multi-point marker mapping
    1. Preparing data for analysis
    2. Running CRI-MAP
    3. The other LINKAGE programs
  9. Data cleaning prior to linkage analysis
    1. Programs
    2. Detecting errors at a single locus
    3. Detecting errors using multiple loci
  10. Phenometric quantitative trait analyses
  11. Examples of phenometric trait analyses
  12. Step-by-step data cleaning at QIMR
  13. Drawing pedigrees under Unix using Graphviz

Resources

Early chapters from general genetics text books eg:

Ott J. Human genetic linkage. Baltimore: Johns Hopkins, 1992.

Terwilliger JD, Ott J. Handbook of human genetic linkage. Baltimore: Johns Hopkins, 1994. Chapters 1-12.

Weir, BS. Genetic data analysis II. Sunderland: Sinauer, 1995.

Computer programs