Haplotyping a Quantitative Trait with a High-Density Map in Experimental Crosses

Wei Hou,James M Cheverud,Song Wu,Tian Liu,John Stephen F Yap,Rongling Wu

doi:10.1371/journal.pone.0000732

Abstract

BackgroundThe ultimate goal of genetic mapping of quantitative trait loci (QTL) is the positional cloning of genes involved in any agriculturally or medically important phenotype. However, only a small portion (≤ 1%) of the QTL detected have been characterized at the molecular level, despite the report of hundreds of thousands of QTL for different traits and populations.Methods/ResultsWe develop a statistical model for detecting and characterizing the nucleotide structure and organization of haplotypes that underlie QTL responsible for a quantitative trait in an F2 pedigree. The discovery of such haplotypes by the new model will facilitate the molecular cloning of a QTL. Our model is founded on population genetic properties of genes that are segregating in a pedigree, constructed with the mixture-based maximum likelihood context and implemented with the EM algorithm. The closed forms have been derived to estimate the linkage and linkage disequilibria among different molecular markers, such as single nucleotide polymorphisms, and quantitative genetic effects of haplotypes constructed by non-alleles of these markers. Results from the analysis of a real example in mouse have validated the usefulness and utilization of the model proposed.ConclusionThe model is flexible to be extended to model a complex network of genetic regulation that includes the interactions between different haplotypes and between haplotypes and environments.

Highlights

The basic principle for quantitative trait locus (QTL) mapping is the cosegregation of the alleles at a quantitative trait loci (QTL) with those at one or a set of known polymorphic markers genotyped on a genome in an experimental cross [1,2]
Because the marker data we have for mouse are microsatellites rather than single nucleotide polymorphisms (SNPs), we use these microsatellite markers as a surrogate of SNPs for the purpose to demonstrate the utility of the model
Quantitative trait locus (QTL) mapping aims to identify narrow chromosomal segments for a quantitative trait by using a statistical method, and has proven its value to study the genetic architecture of the trait in a variety of species [6,7,8]

Summary

Introduction

The basic principle for quantitative trait locus (QTL) mapping is the cosegregation of the alleles at a QTL with those at one or a set of known polymorphic markers genotyped on a genome in an experimental cross [1,2]. If a QTL is cosegregating with molecular markers, the genetic effects of the QTL on a quantitative trait and its genomic position can be estimated from the marker genotypes and phenotypic values of the trait This estimation process assumes the QTL to be located within an interval constructed by a pair of flanking markers in which a test statistics calculated under the reduced (there is no QTL) and full model (there is a QTL) is used to test the existence of the QTL and estimate its position. We develop a statistical model for detecting and characterizing the nucleotide structure and organization of haplotypes that underlie QTL responsible for a quantitative trait in an F2 pedigree The discovery of such haplotypes by the new model will facilitate the molecular cloning of a QTL. The model is flexible to be extended to model a complex network of genetic regulation that includes the interactions between different haplotypes and between haplotypes and environments

Methods

Results

Conclusion