January 2017

evolution of QTL models

original ideas focused on rare & costly markers
models & methods refined as technology advanced

  • single marker regression
  • QTL (quantitative trait loci)
    • single locus models: interval mapping for QTL
    • QTL model search: QTLs & epistasis
  • polygenes (association mapping)
    • adjust for population structure
    • capture "missing heritability"
  • genome-wide selection

what is genomic selection?

use statistical modeling to predict how a plant will perform
before it is field-tested

  • genomic selection (GS)
    • marker assisted selection (MAS)
    • genome-wide selection (GS)
  • other uses of word (relevent to systems genetics)
    • natural selection: survival of the fittest
    • model selection: search for QTLs
    • selection bias: overestimate of QTL effects

why use genomic selection?

  • trait is highly polygenic (genetically variable)
    • influenced by a few key genomic regions
    • high heritability (low environmental variation)
  • measuring trait is costly
    • difficult or expensive process (technology)
    • measuring tool may be highly variable
    • time-consuming (plant has to grow first)
    • desire to streamline multi-year selection

what is genomic selection?

  • forms of genome-wide selection
    • marker-assisted: with phenotypes
    • marker-based: without phenotypes
  • use markers to improve selection for complex traits
    • predict phenotype from marker genotype
    • select candidates based on best marker genotypes
    • use training set to predict test set of individuals

old paradigm: marker prediction

  • 1990s & 2000s: markers were expensive
  • economic strategy:
    • first identify significant markers (QTL analysis)
    • use best markers to genotype selection candidates
  • estimate marker effects by multiple regression
    • treat genetic effects as fixed and few
    • \(E(y)= \mu_q, q=(q_1,q_2,q_3)\)

marker assisted selection (MAS)

www.21stcentech.com/heard-marker-assisted-breeding/

new paradigm: use "all" markers

  • new paradigm with technology advances
    • improved statistical methods and software
    • cheap markers
  • using only significant markers to predict trait …
    • gives good estimates (maybe) of markers …
    • but does not maximize accuracy
  • simple but effective approach
    • treat marker effects as random
    • use all markers (away from QTL if any)

old vs new

old vs new GS

mixed model approach

MAS approach \(y = \mu_q + e, V(e) = \sigma^2I\)

  • estimate fixed QTL effects \(\hat{\mu}_q\) (MLEs)
  • predict phenotype using fixed effects \(\hat{y}=\hat{\mu}_q\)

GS approach \(y = \mu + g + e, V(g) = \sigma_g^2K\)

  • estimate kinship \(K\) from all markers \(M\) as for poly
  • predict random effect \(\hat{g}\) using BLUP
  • predict phenotype \(\hat{y}=\hat{g}\)

genomic prediction

rrBLUP DO poly

  • DO example
  • rrBLUP fit without QTL
  • correlation 0.79

poly + QTL genomic prediction

rrBLUP DO QTL

  • DO example
  • rrBLUP fit with QTL
  • correlation 0.74