DOQTL

DOQTL performs quantitative trait locus (QTL) mapping in Diversity Outbred (DO) mice and other multiparent outbred populations by reconstructing founder haplotypes and enabling linkage and association analyses to identify loci underlying complex traits.

Key Features:

• Haplotype Reconstruction: Employs a hidden Markov model (HMM) to probabilistically reconstruct founder haplotypes from genotyping array intensity data and outputs haplotype probabilities.
• Linkage and Association Mapping: Performs linkage mapping using reconstructed haplotype probabilities and, when founder sequences are available, imputes founder sequences onto DO genomes to enable association mapping that accounts for multiple founder alleles.
• Handling Complex Breeding Designs: Implements regression models that accommodate multiple founder alleles and account for polygenic covariance among related animals arising from complex breeding designs.
• Power Analysis: Provides power analysis indicating that studies with ~200 DO mice can detect loci with large effects, whereas loci explaining <5% of trait variance may require up to ~1000 animals.

Scientific Applications:

• QTL mapping in multiparent populations: Maps genes and loci underlying complex phenotypes in model organisms such as Diversity Outbred mice by leveraging increased recombination density and multi-founder allelic diversity.

Methodology:

Uses hidden Markov models for haplotype reconstruction from genotyping array intensity data; regression-based mapping methods that consider multiple founder haplotypes and relatedness among animals; and imputation of founder sequences onto DO genomes when founder sequences are available.