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

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