K E Browman1, J C Crabbe. 1. Portland Alcohol Research Center, Department of Veterans Affairs Medical Center and Department of Behavioral Neuroscience, Oregon Health Sciences University, 97201, USA. browmank@ohsu.edu
Abstract
BACKGROUND: Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. METHODS: We conducted a QTL analysis of ethanol-induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen. RESULTS: Genome-wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p < or = 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 13, and X, and several map near potential candidate genes. CONCLUSIONS: These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.
BACKGROUND: Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. METHODS: We conducted a QTL analysis of ethanol-induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen. RESULTS: Genome-wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p < or = 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 13, and X, and several map near potential candidate genes. CONCLUSIONS: These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.
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