A Random-Model Approach to QTL Mapping in Multiparent Advanced Generation Intercross (MAGIC) Populations

Genetics. 2016 Feb;202(2):471-86. doi: 10.1534/genetics.115.179945. Epub 2015 Dec 29.

Abstract

Most standard QTL mapping procedures apply to populations derived from the cross of two parents. QTL detected from such biparental populations are rarely relevant to breeding programs because of the narrow genetic basis: only two alleles are involved per locus. To improve the generality and applicability of mapping results, QTL should be detected using populations initiated from multiple parents, such as the multiparent advanced generation intercross (MAGIC) populations. The greatest challenges of QTL mapping in MAGIC populations come from multiple founder alleles and control of the genetic background information. We developed a random-model methodology by treating the founder effects of each locus as random effects following a normal distribution with a locus-specific variance. We also fit a polygenic effect to the model to control the genetic background. To improve the statistical power for a scanned marker, we release the marker effect absorbed by the polygene back to the model. In contrast to the fixed-model approach, we estimate and test the variance of each locus and scan the entire genome one locus at a time using likelihood-ratio test statistics. Simulation studies showed that this method can increase statistical power and reduce type I error compared with composite interval mapping (CIM) and multiparent whole-genome average interval mapping (MPWGAIM). We demonstrated the method using a public Arabidopsis thaliana MAGIC population and a mouse MAGIC population.

Keywords: MPP; Multiparent Advanced Generation Inter-Cross (MAGIC); best linear unbiased prediction; empirical Bayes; mixed model; multiparental populations; polygene; restricted maximum likelihood.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Arabidopsis / genetics
  • Chromosome Mapping*
  • Computer Simulation
  • Crosses, Genetic*
  • Founder Effect
  • Genetics, Population*
  • Genome-Wide Association Study
  • Mice
  • Models, Genetic*
  • Models, Statistical
  • Multifactorial Inheritance
  • Quantitative Trait Loci*