Genomewide search for epistasis in a complex trait

Pentobarbital withdrawal convulsions in mice

Heather M. Hood, John Belknap, John Jr Crabbe, Kari Buck

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 B6D2F2 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.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalBehavior Genetics
Volume31
Issue number1
DOIs
StatePublished - 2001

Fingerprint

epistasis
pentobarbital
Pentobarbital
seizures
modifiers (genes)
Quantitative Trait Loci
chromosome
Seizures
genome
quantitative trait loci
gene
mice
loci
phenotype
genomics
allele
genetic variance
Genome
chromosomes
Chromosomes, Human, Pair 11

Keywords

  • B6D2 F intercross
  • BXD
  • C57BL/6
  • DBA/2
  • Epistasis
  • Gene interaction
  • Genetic mapping
  • Pentobarbital withdrawal
  • Recombinant inbred strains

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Behavioral Neuroscience
  • Psychology(all)

Cite this

Genomewide search for epistasis in a complex trait : Pentobarbital withdrawal convulsions in mice. / Hood, Heather M.; Belknap, John; Crabbe, John Jr; Buck, Kari.

In: Behavior Genetics, Vol. 31, No. 1, 2001, p. 93-100.

Research output: Contribution to journalArticle

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