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  • Journal article
    Cookson WOC, 2006,

    State of the art. Genetics and genomics of chronic obstructive pulmonary disease.

    , Proc Am Thorac Soc, Vol: 3, Pages: 473-475, ISSN: 1546-3222
  • Journal article
    Valdar W, Solberg LC, Gauguier D, Burnett S, Klenerman P, Cookson WO, Taylor MS, Rawlins JNP, Mott R, Flint Jet al., 2006,

    Genome-wide genetic association of complex traits in heterogeneous stock mice.

    , Nat Genet, Vol: 38, Pages: 879-887, ISSN: 1061-4036

    Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.
  • Conference paper
    Morar N, Harper J, Cookson WO, Moffatt MFet al., 2006,

    Filaggrin mutations in atopic dermatitis

    , 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR), Publisher: NATURE PUBLISHING GROUP, Pages: 38-38, ISSN: 0022-202X
  • Journal article
    Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C, Bhalla KN, Zhu T, Ito Y, Sukumar Set al., 2006,

    RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer.

    , Cancer Res, Vol: 66, Pages: 6512-6520, ISSN: 0008-5472

    A tumor suppressor function has been attributed to RUNX3, a member of the RUNX family of transcription factors. Here, we examined alterations in the expression of three members, RUNX1, RUNX2, and RUNX3, and their interacting partner, CBF-beta, in breast cancer. Among them, RUNX3 was consistently underexpressed in breast cancer cell lines and primary tumors. Fifty percent of the breast cancer cell lines (n = 19) showed hypermethylation at the promoter region and displayed significantly lower levels of RUNX3 mRNA expression (P < 0.0001) and protein (P < 0.001). In primary Singaporean breast cancers, 9 of 44 specimens showed undetectable levels of RUNX3 by immunohistochemistry. In 35 of 44 tumors, however, low levels of RUNX3 protein were present. Remarkably, in each case, protein was mislocalized to the cytoplasm. In primary tumors, hypermethylation of RUNX3 was observed in 23 of 44 cases (52%) and was undetectable in matched adjacent normal breast epithelium. Mislocalization of the protein, with or without methylation, seems to account for RUNX3 inactivation in the vast majority of the tumors. In in vitro and in vivo assays, RUNX3 behaved as a growth suppressor in breast cancer cells. Stable expression of RUNX3 in MDA-MB-231 breast cancer cells led to a more cuboidal phenotype, significantly reduced invasiveness in Matrigel invasion assays, and suppressed tumor formation in immunodeficient mice. This study provides biological and mechanistic insights into RUNX3 as the key member of the family that plays a role in breast cancer. Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment.
  • Journal article
    Griesenbach U, Geddes DM, Alton EWFW, 2006,

    Gene therapy progress and prospects: cystic fibrosis

    , GENE THERAPY, Vol: 13, Pages: 1061-1067, ISSN: 0969-7128
  • Journal article
    Morar N, Willis-Owen SAG, Moffatt MF, Cookson WOCMet al., 2006,

    The genetics of atopic dermatitis

    , JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 118, Pages: 24-34, ISSN: 0091-6749
  • Journal article
    Haibach K, Menner A, Powell R, Bismarck Aet al., 2006,

    Tailoring mechanical properties of highly porous polymer foams: Silica particle reinforced polymer foams via emulsion templating

    , POLYMER, Vol: 47, Pages: 4513-4519, ISSN: 0032-3861
  • Journal article
    Adcock IM, Caramori G, Ito K, 2006,

    New insights into the molecular mechanisms of corticosteroids actions

    , CURRENT DRUG TARGETS, Vol: 7, Pages: 649-660, ISSN: 1389-4501
  • Journal article
    Tanabe M, Atkins HS, Harland DN, Elvin SJ, Stagg AJ, Mirza O, Titball RW, Byrne B, Brown KAet al., 2006,

    The ABC transporter protein OppA provides protection against experimental <i>Yersinia pestis</i> infection

    , INFECTION AND IMMUNITY, Vol: 74, Pages: 3687-3691, ISSN: 0019-9567
  • Journal article
    Menner A, Powell R, Bismarck A, 2006,

    A new route to carbon black filled polyHIPEs

    , SOFT MATTER, Vol: 2, Pages: 337-342, ISSN: 1744-683X

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