Practical Applications of the Bioinformatics Toolbox for Narrowing Quantitative Trait Loci

Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable expressivity of traits. Although quantitative trait locus (QTL) analysis has been a powerful tool...

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Bibliographic Details
Published in:Genetics (Austin) 2008-12, Vol.180 (4), p.2227-2235
Main Authors: Burgess-Herbert, Sarah L, Cox, Allison, Tsaih, Shirng-Wern, Paigen, Beverly
Format: Article
Language:English
Subjects:
Animals
Bioinformatics
Bone density
Chromosomes
Computational Biology - methods
Confidence intervals
Crosses, Genetic
Databases, Genetic
Endangered & extinct species
Gene mapping
Genes
Genetic engineering
Genomics
Haplotypes
Investigations
Lipoproteins, HDL - genetics
Mice
Organisms
Quantitative Trait Loci
Standard deviation
Statistical methods
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Summary:Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable expressivity of traits. Although quantitative trait locus (QTL) analysis has been a powerful tool for localizing the chromosomal regions underlying complex traits, systematically identifying the causal genes remains challenging. Here, through its application to plasma levels of high-density lipoprotein cholesterol (HDL) in mice, we demonstrate a strategy for narrowing QTL that utilizes comparative genomics and bioinformatics techniques. We show how QTL detected in multiple crosses are subjected to both combined cross analysis and haplotype block analysis; how QTL from one species are mapped to the concordant regions in another species; and how genomewide scans associating haplotype groups with their phenotypes can be used to prioritize the narrowed regions. Then we illustrate how these individual methods for narrowing QTL can be systematically integrated for mouse chromosomes 12 and 15, resulting in a significantly reduced number of candidate genes, often from hundreds to
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.108.090175