Genomewide Search for Epistasis in a Complex Trait: Pentobarbital Withdrawal Convulsions in Mice

Author: Hood H.M.   Belknap J.K.   Crabbe J.C.   Buck K.J.  

Publisher: Springer Publishing Company

ISSN: 0001-8244

Source: Behavior Genetics, Vol.31, Iss.1, 2001-01, pp. : 93-100

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Abstract

The well-documented difference in pentobarbital withdrawal severity between DBA/2J and C57BL/6J mice offers the opportunity to study how differences between allelic variants influence pentobarbital withdrawal via their additive and/or dominance effects and to identify modifier loci that also influence the trait via gene-gene interactions (a form of epistasis). Previous work in our laboratory identified seven provisional quantitative trait loci (QTLs) for pentobarbital withdrawal using BXD recombinant inbred strains. To date, only one of these QTLs has been confirmed, Pbwl. We hypothesized that other loci that act epistatically may also influence genetic variance in pentobarbital withdrawal severity. Using Epistat, a program developed to carry out full-genome searches for epistasis, we identified six provisional epistatic interactions (p < .002)="" between="" the="" provisional="" qtls="" and="" modifier="" loci="" elsewhere="" in="" the="" genome.="" verification="" testing="" of="" these="" interactions="" using="" 404="" b6d2f_2="" mice="" provided="" supporting="" evidence="" that="" a="" qtl="" on="" chromosome="" 11="" contributes="" to="" genetic="" variance="" in="" pentobarbital="" withdrawal,="" but="" only="" in="" the="" presence="" of="" a="" modifier="" allele="" on="" distal="" chromosome="" 1="" (p=".0004)." this="" modifier="" is="" in="" the="" same="" genomic="" vicinity="" as="" loci="" detected="" for="" a="" variety="" of="" withdrawal="" and="" seizure="" phenotypes.="">

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