Chromosomal loci influencing chronic alcohol withdrawal severity

Susan E. Bergeson, R. Kyle Warren, John C. Crabbe, Pamela Metten, V. Gene Erwin, John K. Belknap

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Ethanol (alcohol) withdrawal-induced convulsions are a key index of physical dependence on ethanol and a clinically important consequence of alcohol abuse in humans. In rodent models, severity of withdrawal is strongly influenced by genotype. For example, many studies have reported marked differences in withdrawal severity between the WSR (Withdrawal Seizure Resistant) and WSP (Withdrawal Seizure Prone) mouse strains selectively bred for over 25 generations to differ in chronic withdrawal severity. Therefore, we used an F2 intercross between the inbred WSP and WSR strains for a genome-wide search for quantitative trait loci (QTLs), which are chromosomal sites containing genes influencing the magnitude of withdrawal. We also used the recently developed HW, RHW (high withdrawal) and LW, RLW (low withdrawal) lines selectively bred for the same trait and in the same manner as the WSP, WSR lines. QTL analysis was then used to dissect the continuous trait distribution of withdrawal severity into component loci, and to map them to broad chromosomal regions by using the Pseudomarker 0.9 and Map Manager QT29b programs. This genome-wide search identified five significant QTLs influencing chronic withdrawal severity on Chromosomes (Chrs) 1 (proximal), 4 (mid), 8 (mid), 11 (proximal), and 14 (mid), plus significant interactions (epistasis) between loci on Chr 11 with 13, 4 with 8, and 8 with 14.

Original languageEnglish (US)
Pages (from-to)454-463
Number of pages10
JournalMammalian Genome
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Genetics

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    Bergeson, S. E., Warren, R. K., Crabbe, J. C., Metten, P., Erwin, V. G., & Belknap, J. K. (2003). Chromosomal loci influencing chronic alcohol withdrawal severity. Mammalian Genome, 14(7), 454-463. https://doi.org/10.1007/s00335-002-2254-4