Serious limitations of the QTL/microarray approach for QTL gene discovery.

BMC Biology
Ricardo A VerdugoJuan F Medrano

Abstract

It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed. Thirty-seven studies that have implemented the QTL/microarray approach in rodents were reviewed. About 30% of studies showed enrichment for QTL candidates, mostly in comparisons between congenic and background strains. Three studies led to the identification of an underlying QTL gene. To complement the literature results, a microarray experiment was performed using three mouse congenic strains isolating the effects of at least 25 biometric QTL. Results show that genes in the congenic donor regions were preferentially selected. However, within donor regions, the distribution of differentially expressed genes was homogeneous once gene density was accounted for. Genes within identical-by-descent (IBD) regions were less likely to be differentially expressed in chromosome 2, but not in chromosomes 11 and 17. Furthermore, expression of QTL regulated in cis (cis eQTL) showed higher expression in the background genotype, which was partially explained by the prese...Continue Reading

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Datasets Mentioned

BETA
GSE22042

Methods Mentioned

BETA
dissection
transgenic
genotyping
gene trap
dissecting

Software Mentioned

Bioconductor
BeadStudio
affy
R
Ensembl genome browser
UCSC Genome Browser
CAST
Maanova
CGD Strain Comparison
BLAT

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