The Role of Epistasis in the Control of Complex Traits

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The Role of Epistasis in the Control of Complex
Traits

• Örjan Carlborg and Chris Haley
• Roslin Institute

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Epistasis

• Epistasis interactions between alleles at
  different loci
• Relatively neglected in quantitative genetics
• More attention in qualitative genetics where
  several types of epistasis has been found for
  e.g. coat colour phenotypes

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Examples of classic epistasis
Hybrid dysgenesis
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Epistasis and QTL

• Most QTL mapping studies focus on detection of
  marginal effects assuming absence of epistasis
• Assumption of no epistasis based on low estimates
  of epistatic variances from quantitative genetic
  studies
• Some studies have searched for epistasis between
  QTL with significant marginal effects

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Why consider epistasis?

• Similar cellular mechanisms affect quantitative
  and qualitative traits
• Increased power to detect QTL which mediate their
  effects through interactions
• Epistasis could bias estimates of additive and
  dominance effects
• Epistasis could help in the interpretations of
  QTL mapping results

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Methodology to detect epistasis

• Need procedure to detect QTL with marginal
  effects as well as entirely epistatic QTL
• One option (Carlborg and Andersson, 2002)

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Increased power to detect QTL

• Possible to detect novel QTL pairs with very
  small or no marginal effects at all possible for
  the individual QTL
• Increased support for QTL with close to
  significant marginal effects

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New epistatic QTL detected

• Some QTL can not be detected by their marginal
  effects
• E.g. QTL pair affecting hatch weight in chicken

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New epistatic QTL detected

• Simultaneous mapping of epistatic QTL increases
  significance for some QTL with minor marginal
  effects

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Bias in estimation of QTL effects

• Estimates of marginal genetic effects are the
  average effect of the alleles at a locus across
  all alleles at all other genomic loci
• By identifying interactions between loci one can
  obtain additional information about e.g.
• In which genetic background a QTL has its most
  influential effects
• How further studies should be designed to
  maximise the chance to replicate a QTL

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Bias in estimation of QTL effects
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Additional variance explained

• The estimates of the relative amount of variance
  attributable to epistasis depend on the genetic
  model used in the study
• The simplest and most commonly used model is that
  of Mather and Jinks
• Alternatives include the Cockerham model

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Additional variance explained

• Epistasis explains a considerable portion of the
  genetic variance (Mather-Jinks model)

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Genetic mechanisms of epistasis

• By understanding more about the nature of QTL
  interactions, one can
• Be more precise when selecting candidate genes
• Better select the strategy for replicating a QTL
• Get higher efficiency in marker assisted
  selection (MAS)
• Need to explore Genotype-Phenotype patterns for
  epistatic QTL

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Genetic mechanisms of epistasis

• Chicken F2 intercross between growth and layer
  selection lines
• 21 epistatic QTL pairs detected
• 17 pairs could be associated with one of 4 types
  of epistasis

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Genetic mechanisms of epistasis

• Chicken F2 intercross 4 common types of
  epistasis

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Conclusions

• Epistasis is abundant
• Epistasis increases power in QTL mapping
• Novel QTL detected and more variance explained
• Epistasis might be needed to replicate QTL
  findings and clone QTL
• Can not understand control of complex traits
  without considering epistasis

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Acknowledgements

• Roslin Institute
• Dave Burt, Paul Hocking, DJ deKoning
• Swedish University of Agricultural Sciences
• Leif Andersson, Per Jensen, Susanne Kerje, Karin
  Schutz
• The Knut and Alice Wallenberg foundation
• NGSSC
• BBSRC