R/qtl2: Software for Mapping Quantitative Trait Loci with High-Dimensional Data and Multiparent Populations

Abstract

R/qtl2 is an interactive software environment for mapping quantitative trait loci (QTL) in experimental populations. The R/qtl2 software expands the scope of the widely used R/qtl software package to include multiparent populations derived from more than two founder strains, such as the Collaborative Cross and Diversity Outbred mice, heterogeneous stocks, and MAGIC plant populations. R/qtl2 is designed to handle modern high-density genotyping data and high-dimensional molecular phenotypes, including gene expression and proteomics. R/qtl2 includes the ability to perform genome scans using a linear mixed model to account for population structure, and also includes features to impute SNPs based on founder strain genomes and to carry out association mapping. The R/qtl2 software provides all of the basic features needed for QTL mapping, including graphical displays and summary reports, and it can be extended through the creation of add-on packages. R/qtl2, which is free and open source software written in the R and C++ programming languages, comes with a test framework.

Keywords: Collaborative Cross; Diversity Outbred mice; MAGIC; MPP; Multiparent Advanced Generation Inter-Cross (MAGIC); QTL; heterogeneous stock; multiparent populations; software.

Figure 1

Reconstruction of Figure 5 from Gatti et al. (2014), on the mapping of constitutive neutrophil counts in 742 DO mice. (A) LOD scores from a genome scan using the full model (comparing all 36 genotypes for the autosomes and 44 genotypes for the X chromosome); the dashed horizontal line indicates the 5% genome-wide significance threshold, based on a permutation test. (B) LOD scores from a genome scan with an additive allele model (comparing the eight founder haplotypes). (C) LOD scores from a SNP association scan, using all SNPs that were genotyped in the eight founder lines. (D) BLUPs of the eight haplotype effects in the additive model, along with the LOD curve on chromosome 1. (E) SNP association results in the region of the chromosome 1 QTL, along with genes in the region; SNPs with LOD scores within 1.5 of the maximum are highlighted in pink. All figures are produced with R/qtl2.

Figure 2

Analysis of 19-way Arabidopsis MAGIC data from Gnan et al. (2014) for three traits. (A–C) LOD curves with the results from Gnan et al. (2014) in blue, and from R/qtl2 in pink. (D–F) QTL effects from Table 5 of Gnan et al. (2014) (blue), by linear regression from R/qtl2 (pink), and BLUPs from R/qtl2 (green).