TABLE 2

Application of LCL models to pharmacogenomics

LCL-Based ModelGenetic ApproachEndophenotypePhenotypeReference
Pregenomic era (before 2003)
    Patients with HNSCC and unaffected family membersHeritabilityDrug sensitivityCloos et al., 1999
    Patients with MS and unaffected family membersHeritabilitySensitivity to ionizing radiationGipps and Kidson, 1984
    Patients with Wilms' tumorCandidate geneDrug sensitivityImray et al., 1984
    Patients with Werner syndromeCandidate geneDrug sensitivityPoot et al., 1999
    Postgenomic era (2003 to present)
    CEPH PedigreesHeritability, linkage analysisExpressionMorley et al., 2004
    HapMap trioseQTLExpressionCheung et al., 2005; Stranger et al., 2005; Spielman et al., 2007; Storey et al., 2007; Stranger et al., 2007a,b; Duan et al., 2008; Huang et al., 2008d; Zhang et al., 2008, 2009; Kudaravalli et al., 2009
    CEPH PedigreesHeritability, linkage analysisDrug sensitivityDolan et al., 2004; Watters et al., 2004
    CEPH Pedigrees/HapMap triosHeritability, linkage-directed association studiesDrug sensitivityDuan et al., 2007; Shukla et al., 2008, 2009; Bleibel et al., 2009
    CEPH pedigreesLinkage analysis, association studiesExpressionResponse to ionizing radiationSmirnov et al., 2009
    Human Variation PanelTranscriptional profilingDrug sensitivityLi et al., 2008
    Patients with breast cancer, with and without BRCA1/2 mutationsTranscriptional profilingResponse to ionizing radiationWaddell et al., 2008
    HapMap triosTranscriptional profilingDrug sensitivityFry et al., 2008
    Subjects with HNSCC and control subjectsTranscriptional profilingDrug sensitivityCloos et al., 2006
    SOPHIE populationCandidate geneAllelic imbalanceUrban et al., 2006; Tahara et al., 2009
    Polymorphism Discovery ResourceCandidate geneAllelic imbalancePoonkuzhali et al., 2008
    HapMap triosCandidate geneAllelic imbalanceJohnson et al., 2008
    Subjects with type 2 diabetes and control subjectsCandidate geneAllelic imbalanceElbein et al., 2007
    HapMap triosCandidate geneDrug sensitivityHartford et al., 2009
    Human Variation PanelCandidate geneDrug sensitivityWang et al., 2008
    Human Variation Panel/CEPH unrelatedsCandidate geneDrug sensitivityInnocenti et al., 2009
    Schizophrenia case-control studyCandidate geneExpressionChagnon et al., 2008
    HapMap triosGWASExpressionDrug sensitivityHuang et al., 2007a,b, 2008b,c,; Hartford et al., 2009

  • HNSCC, head and neck squamous cell carcinoma; MS, multiple sclerosis.