Harnessing the mouse to unravel the genetics of human disease

T. J. Phillips, John Belknap, R. J. Hitzemann, Kari Buck, Christopher Cunningham, John Jr Crabbe

Research output: Contribution to journalReview articlepeer-review

66 Scopus citations


Complex traits, i.e. those with multiple genetic and environmental determinants, represent the greatest challenge for genetic analysis, largely due to the difficulty of isolating the effects of any one gene amid the noise of other genetic and environmental influences. Methods exist for detecting and mapping the Quantitative Trait Loci (QTLs) that influence complex traits. However, once mapped, gene identification commonly involves reduction of focus to single candidate genes or isolated chromosomal regions. To reach the next level in unraveling the genetics of human disease will require moving beyond the focus on one gene at a time, to explorations of pleiotropism, epistasis and environment-dependency of genetic effects. Genetic interactions and unique environmental features must be as carefully scrutinized as are single gene effects. No one genetic approach is likely to possess all the necessary features for comprehensive analysis of a complex disease. Rather, the entire arsenal of behavioral genomic and other approaches will be needed, such as random mutagenesis, QTL analyses, transgenic and knockout models, viral mediated gene transfer, pharmacological analyses, gene expression assays, antisense approaches and importantly, revitalization of classical genetic methods. In our view, classical breeding designs are currently underutilized, and will shorten the distance to the target of understanding the complex genetic and environmental interactions associated with disease. We assert that unique combinations of classical approaches with current behavioral and molecular genomic approaches will more rapidly advance the field.

Original languageEnglish (US)
Pages (from-to)14-26
Number of pages13
JournalGenes, Brain and Behavior
Issue number1
StatePublished - Jan 2002


  • Classical Genetics
  • ENU mutagenesis
  • Epistasis
  • Gene expression
  • Genomics
  • Inbred strains
  • QTL mapping
  • Selected lines

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience


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