epistatic variation
Mackay TFC 2009 Mutations and quantitative genetic variation: lessons from Drosophila. Phil Trans R Soc Lond B 365:1229-1239.
- classical variance component analyses generally show little, if any, contribution of epistatic interactions to the total genetic variance for most quantitative traits
- epistasis is difficult to detect using these designs
- even strong epistatic interactions contribute little epistatic variance
- the epistatic interaction term has a high sampling variance, requiring huge sample sizes for detection
- detecting epistasis is also difficult in QTL mapping studies
- the large number of pair-wise tests for marker-marker interactions imposes a low experiment-wise significance threshold
- large mapping populations are required to sample individuals in the rarer two-locus genotype classes
- segregation of other QTLs can interfere with detecting epistasis between the pair of loci under consideration
- epistasis is more readily detectable in crosses among lines in which genetic heterogeneity is reduced, the genetic background is controlled precisely, and allele frequencies are intermediate
- DNA sequence variation does not affect quantitative traits directly, but does so through networks of intermediate molecular phenotypes
- understanding the relationship between DNA sequence variation, transcriptional, protein and metabolite networks and organismal-level phenotypes is the main challenge for the future and will add the missing biological context to genotype–phenotype associations
- this 'systems genetics' approach to understanding the quantitative genetic variation is best applied to a reference panel of inbred lines, newly derived from nature
