Further studies on using multiple-cross mapping (MCM) to map quantitative trait loci

Abstract

We have completed whole-genome scans for quantitative trait loci (QTLs) associated with acute ethanol-induced activation in the six F(2) intercrosses that can be formed from the C57BL/6J (B6), DBA/2J (D2) , BALB/cJ (C), and LP/J (LP) inbred strains. The goal was to test the hypothesis that given the relatively simple structure of the laboratory mouse genome, the same QTLs will be detected in multiple crosses which in turn will provide support for the strategy of multiple-cross mapping (MCM). QTLs with LOD scores greater than 4 were detected on Chrs 1, 2, 3, 8, 9, 13, 14, and 16. Only for the QTL on distal Chr 1 was there convincing evidence that the same or at least a very similar QTL was detected in multiple crosses. We also mapped the Chr 2 QTL directly in heterogeneous stock (HS) animals derived from the four inbred strains. At G(19) the QTL was mapped to an approximately 3-Mbp interval and this interval was associated with a haplotype block with a largely biallelic structure: B6-L:C-D2. We conclude that mapping in HS animals not only provides significantly greater QTL resolution, at least in some cases it provides significantly more information about the QTL haplotype structure.

The genetics of gene expression in complex mouse crosses as a tool to study the molecular underpinnings of behavior traits

“…Nonetheless and not unexpectedly, the number of “true” cis -eQTLs appeared to be significantly greater than those previously detected in simpler crosses; i.e., in the HS population, additional regulatory alleles are detected. Similar results were obtained for gene expression in a simpler HS (HS4), derived from crossing four laboratory strains (Malmanger et al 2006). …”

Treatment- and Population-Dependent Activity Patterns of Behavioral and Expression QTLs

“…In the LXS population, the two significant QTLs regulated behavior in the EC group, which included treatment with ethanol but not restraint stress. The Chr 3 QTL, associated with activity count, is located near several previously identified QTLs that have been linked to ethanol-induced locomotion [18], [36] and ethanol-induced loss of righting response [17]. We have previously investigated the Chr 3 QTL which encompasses a cluster of alcohol dehydrogenase genes.…”

A Combined-Cross Analysis Reveals Genes With Drug-Specific and Background-Dependent Effects on Drug Sensitivity in Saccharomyces cerevisiae

“…Combined-cross analysis provides increased power and resolution due to larger sample sizes but also provides a means of identifying QTL with effects that depend on their genetic background (Li et al 2005;Blanc et al 2006;Guo et al 2006;Jagodic and Olsson 2006;Malmanger et al 2006). A number of lines of evidence suggest that many of the drug-sensitivity QTL that we identified have effects that depend on their genetic background.…”