title: A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.
abstract: The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F(2) intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F(2) offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR) and blood ethanol at regain of the righting reflex (BECRR). F(2) rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2 and 3. Highly significant QTLs for LORR duration (LOD = 12.4) and BECRR (LOD = 5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA. richard.radcliffe@ucdenver.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Radcliffe
authors.forename: V G
authors.initials: VG
authors.lastname: Erwin
authors.forename: P
authors.initials: P
authors.lastname: Bludeau
authors.forename: X
authors.initials: X
authors.lastname: Deng
authors.forename: T
authors.initials: T
authors.lastname: Fay
authors.forename: K L
authors.initials: KL
authors.lastname: Floyd
authors.forename: R A
authors.initials: RA
authors.lastname: Deitrich
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics* / Q000503:physiopathology; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D020296:Animals, Congenic; D001259:Ataxia / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D004361:Drug Tolerance / Q000235:genetics* / Q000502:physiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D008297:Male; D040641:Quantitative Trait Loci / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013045:Species Specificity
chemical_list: D005819:Genetic Markers