AN INTRODUCTION TO GENETIC ASSOCIATION AND LINKAGE ANALYSIS
David Duffy (davidD@qimr.edu.au)
Overview
- Review of classical genetics
- Mendelism
- Linkage
- Basic statistical procedures in classical genetics
- Goodness-of-fit testing of distributions of counts
- The binomial distribution
- The Pearson chi-square
- Segregation ratios
- Linkage in experimental crosses
- Review of elementary population genetics
- Hardy-Weinberg equilibrium
- Linkage equilibrium
- Mutation
- Genetic association studies
- Case-control designs
- Family based designs
- Haplotype Relative Risk
- Transmission Disequilibrium Test
- Tests of cosegregation of trait and marker
- Simple and nonparametric linkage analysis
- Counting methods (as in testcross situation)
- Sib-pair methods
- Affected sib-pair analysis
- Haseman-Elston methods
- Affected pedigree member methods
- APM
- SIMIBD
- Genehunter
- Parametric (LOD score) linkage analysis
- Likelihood
- What is likelihood
- Likelihood for linkage
- Some examples
- MLINK and two-point LOD score linkage analysis
- Preparing data for analysis
- MAKEPED and PREPLINK
- Running MLINK
- Autosomal mendelian traits
- Sex-linked recessives
- Loops and LOOPS
- Age-dependent penetrance
- CRI-MAP and multi-point marker mapping
- Preparing data for analysis
- Running CRI-MAP
- The other LINKAGE programs
- Data cleaning prior to linkage analysis
- Programs
- Detecting errors at a single locus
- Detecting errors using multiple loci
- Phenometric quantitative trait analyses
- Examples of phenometric trait analyses
- Step-by-step data cleaning at QIMR
- Drawing pedigrees under Unix using Graphviz
Resources
Early chapters from general genetics text books eg:
- Lewin B. Genes V. Oxford: OUP, 1994.
- Srb AM, Owen RD, Edgar RS. General genetics. San Francisco: WH Freeman, 1965.
- Strickberger MW. Genetics. New York: Macmillan, 1968.
- Vogel F, Motulsky AG. Human Genetics. Problems and approaches. Berlin: Springer-Verlag.
- Suzuki et al. Genetic analysis. 1984.
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
- Cri-Map
- FASTLINK
- GAS
- Genehunter
- Sib-pair