Julius B. Lucks/Meetings and Notes/SMBE2007/plenary 2

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Contents

Trudy MacKay (NC State): The genetic architecture of complex traits -- lessons from Drosophila

Vocabulary

  • Quantitative Trait Loci (QTL)
  • linkage disequilibrium
  • association mapping
  • pleiotropy

Background

  • master at Dalhausie
  • PhD Edinbrugh
  • Oliver Max Gardener Award
  • Fellow Royal Soc
  • American Acad Arts and Sciences
  • Gender and Env can infect gene expression

Talk

  • across animals and plant populations - huge variation in morphology, behavior, etc.
  • phenotype exhibits approx normal distribution among pops
    • many interacting genes
    • individual small effects
    • expression of alleles sensitive to env.
      • central limit theorem

Questions

  • What are the genes affecting variation of complex traits?
  • What is distribution of allelic effects?
  • Effects of multiple traits (pleiotropy) ?
  • Interactions between genes (epistasis) ?
  • Environmental sensitivities (GEI) ?
  • Molecular basis of allelic variation (QTN) ?

Drosophila Genetic Resources

  • clonable
  • reared in large #'s
  • complete sequence
  • range of complex traits
    • number of sensitive bristles
    • resis. to env. stresses
  • model organisms
    • gen properties of arch of complex traits - transferrable across range of organisms

Approaches to Understanding Complex Traits in Flys

  • Unbiased forward mutagenesis screen
    • induce p-transposable element movement with crosses to cause mutagenesis
  • what p-insert lines are different from non-insert control
  • everything in same background - build own genetic networks
    • all crosses of double heterozygotes?
    • whole genome transcripts useful as well
    • QTL mapping - take 2 gen diff strains, cross (recomb populations - back crosses, F2, recomb genome lines)
      • take genotype, and phenotype - statistical analysis to map chromosomal region (quantitative trait loci) to find

region of chromosome responsible for phenotype - have a statistical significance threshold

        • problem - size of QTLs is large because of sample size
        • with flies, use deficiency strains (bits of chromosome missing) - take deficiency chromosomes that overlap QTL, and do crosses,

can find where QTL allelic variant exists

    • Association mapping - linkage disequilibrium: correlation in gene freq at 2 or more polymorphic loci
      • linkage equil - equal frac of gamete frequencies (disequil if differs from this)
      • disequil might happen because of mutation of gene affecting complex trait - orig entire genome is in disequil,

but over time recomb happens and disequil decoys

      • essentially do QTL at the level of a gene
      • flies - make designer genotypes

Inferences Made in Recent Years

  • results of applying techniques above
  • screen for traits
    • abdominal bristle number
    • sternopleural bristle number
    • life span
    • locomation
    • mating
    • aggressive behavior
  • genes affect multiple traits
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