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
region of chromosome responsible for phenotype - have a statistical significance threshold can find where QTL allelic variant exists but over time recomb happens and disequil decoys
 * 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
 * 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,
 * 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,
 * 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