Genetic dissection of quantitative trait locus for ethanol sensitivity in long- and short-sleep mice.
- Authors
- Bennett, B; Carosone-Link, P; Beeson, M; Gordon, L; Phares-Zook, N; Johnson, T E
- Year
- 2008
- Journal
- Genes, brain, and behavior
- PMID
- 18363857
- DOI
- 10.1111/j.1601-183X.2008.00403.x
Interval-specific congenic strains (ISCS) allow fine mapping of a quantitative trait locus (QTL), narrowing its confidence interval by an order of magnitude or more. In earlier work, we mapped four QTL specifying differential ethanol sensitivity, assessed by loss of righting reflex because of ethanol (LORE), in the inbred long-sleep (ILS) and inbred short-sleep (ISS) strains, accounting for approximately 50% of the genetic variance for this trait. Subsequently, we generated reciprocal congenic strains in which each full QTL interval from ILS was bred onto the ISS background and vice versa. An earlier paper reported construction and results of the ISCS on the ISS background; here, we describe this process and report results on the ILS background. We developed multiple ISCS for each Lore QTL in which the QTL interval was broken into a number of smaller intervals. For each of the four QTL regions (chromosomes 1, 2, 11 and 15), we were successful in reducing the intervals significantly. Multiple, positive strains were overlapped to generate a single, reduced interval. Subsequently, this reduced region was overlaid on previous reductions from the ISS background congenics, resulting in substantial reductions in all QTL regions by approximately 75% from the initial mapping study. Genes with sequence or expression polymorphisms in the reduced intervals are potential candidates; evidence for these is presented. Genetic background effects can be important in detection of single QTL; combining this information with the generation of congenics on both backgrounds, as described here, is a powerful approach for fine mapping QTL.
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|---|---|---|---|---|
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | — | 2020 | → |
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| Use of animal models of alcohol-related behavior. | Crabbe JC | — | 2014 | → |
| Transcriptome analysis of Inbred Long Sleep and Inbred Short Sleep mice. | Darlington TM et al. | — | 2013 | → |
| Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J×129S1/SvImJ inbred mouse cross. | Chesler EJ et al. | — | 2012 | → |
| Treatment- and population-dependent activity patterns of behavioral and expression QTLs. | Ziebarth JD et al. | — | 2012 | → |
| Congenic strains provide evidence that a mapped locus on chromosome 15 influences excitotoxic cell death. | Schauwecker PE | — | 2011 | → |
| A comparison of selected quantitative trait loci associated with alcohol use phenotypes in humans and mouse models. | Ehlers CL et al. | — | 2010 | → |
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| From QTL to candidate gene: a genetic approach to alcoholism research. | Spence JP et al. | — | 2009 | → |