Stat 260: Statistics in Genetics

Sandrine Dudoit and T. P. Speed

Week 6: The affected sib-pair method and extensions

Stat 260: Statistics in Genetics

Sandrine Dudoit and T. P. Speed

Week 6: The affected sib-pair method and extensions

• Introduction
  • Identity by descent
  • The affected sib-pair method
• Genetic model
  • Model for disease susceptibility
  • Population genetic model
  • Segregation model
• Sib-pair conditional IBD probabilities at DS loci
  • Multilocus conditional distribution of inheritance vectors at DS loci given phenotype vector of sibship
  • Constraints for sib-pair conditional IBD probabilities
• Examples
  • Single diallelic random mating DS locus models
    • Strict-recessive model
    • Quasi-recessive model
    • Additive model
    • Strict-dominant model
    • Quasi-dominant model
  • Coverage of ASP triangle
    • Strict-recessive model
    • Random mating and Hardy-Weinberg equilibrium models
  • Some counterexamples
    • Assumption M1 - Monotonicity of penetrances
    • Assumption G1 - Conditional independence of phenotypes given genotypes
    • Examples when
• Sib-pair conditional IBD probabilities at markers
• Sampling model
• Tests of null hypothesis of no linkage
  • Likelihood ratio tests
  • Score test for quasi-recessive and quasi-dominant random mating models
    • Quasi-recessive random mating model
    • Quasi-dominant random mating model
  • Linkage score test
    • No distinction between maternal and paternal sharing
    • Distinction between maternal and paternal sharing
  • Some properties of the ``mean IBD'' statistic
• Incomplete IBD information: single markers
• Incomplete IBD information: multipoint calculation
• References
• About this document ...