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Replication and narrowing of gene expression quantitative trait loci using inbred mice.

ABSTRACT: Gene expression quantitative trait locus (eQTL) mapping has become a powerful tool in systems biology. While many authors have made important discoveries using this approach, one persistent challenge in eQTL studies is the selection of loci and genes that should receive further biological investigation. In this study we compared eQTL generated from gene expression profiling in the livers of two panels of mouse strains: 41 BXD recombinant inbred and 36 Mouse Diversity Panel (MDP) strains. Cis-eQTL, loci in which the transcript and its maximum QTL are colocated, have been shown to be more reproducible than trans-eQTL, which are not colocated with the transcript. We observed that between 9.9 and 12.1% of cis-eQTL and between 2.0 and 12.6% of trans-eQTL replicated between the two panels depending on the degree of statistical stringency. Notably, a significant eQTL hotspot on distal chromosome 12 observed in the BXD panel was reproduced in the MDP. Furthermore, the shorter linkage disequilibrium in the MDP strains allowed us to considerably narrow the locus and limit the number of candidate genes to a cluster of Serpin genes, which code for extracellular proteases. We conclude that this strategy has some utility in increasing confidence and resolution in eQTL mapping studies; however, due to the high false-positive rate in the MDP, eQTL mapping in inbred strains is best carried out in combination with an eQTL linkage study.

SUBMITTER: Gatti DM

PROVIDER: S-EPMC2745627 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Replication and narrowing of gene expression quantitative trait loci using inbred mice.

Gatti Daniel M DM Harrill Alison H AH Harrill Alison H AH Wright Fred A FA Threadgill David W DW Rusyn Ivan I

Mammalian genome : official journal of the International Mammalian Genome Society 20090717 7

Gene expression quantitative trait locus (eQTL) mapping has become a powerful tool in systems biology. While many authors have made important discoveries using this approach, one persistent challenge in eQTL studies is the selection of loci and genes that should receive further biological investigation. In this study we compared eQTL generated from gene expression profiling in the livers of two panels of mouse strains: 41 BXD recombinant inbred and 36 Mouse Diversity Panel (MDP) strains. Cis-eQT ...[more]

PMID: 19609828

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Project description:Aflatoxins are carcinogenic and toxic compounds produced principally by fungal species Aspergillus flavus (Link: Fries) and A. parasiticus (Speare), which are common contaminants of food and feed. Aflatoxins can be found at dangerously high levels and can readily contaminate pre-harvest maize (Zea mays L.) grain. Sources of resistance to aflatoxin accumulation in maize have been identified, however, the highly quantitative nature and complex inheritance of this trait have limited the introgression of aflatoxin accumulation resistance into agronomically desirable lines. Mapping of quantitative trait loci (QTL) was performed on a bi-parental population comprised of 241 F2:3 families derived from the cross of inbred lines Mp705 (susceptible) × Mp719 (resistant). The mapping population was phenotyped in replicated field trials in three environments for resistance to aflatoxin accumulation under artificial inoculation with an A. flavus spore suspension. The genetic linkage map was constructed with 1,276 single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) molecular markers covering a total genetic distance of 1,642 cM across all ten maize chromosomes. Multiple interval mapping revealed that majority of the aflatoxin-reducing alleles and the source for the larger effect QTL identified in this study were contributed from Mp719, the resistant parent. Two QTL identified on chromosome 1 (bin 1.06-1.07) and chromosome 3 (bin 3.09) were the most stable across different environments and when combined, explained 24.6% of the total phenotypic variance across all three environments. Results from the study showed that these chromosomal regions harbor important QTL for influencing aflatoxin accumulation, which is consistent with previous reports with other different mapping populations. These stable QTL were the most promising for controlling aflatoxin accumulation in maize grain. Identifying beneficial alleles derived from Mp719 and closely linked molecular markers through QTL analysis for implementation of MAS could accelerate breeding efforts to reduce aflatoxin accumulation in maize.

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Replication and narrowing of gene expression quantitative trait loci using inbred mice.

Publications

Replication and narrowing of gene expression quantitative trait loci using inbred mice.

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