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  • Journal article
    Taylor JW, Jacobson DJ, Kroken S, Kasuga T, Geiser DM, Hibbett DS, Fisher MCet al., 2000,

    Phylogenetic species recognition and species concepts in fungi

    , FUNGAL GENETICS AND BIOLOGY, Vol: 31, Pages: 21-32, ISSN: 1087-1845
    • Cite
    • Citations: 1511
  • Journal article
    Cookson WO, Moffatt MF, 2000,

    Genetics of asthma and allergic disease.

    , Hum Mol Genet, Vol: 9, Pages: 2359-2364, ISSN: 0964-6906

    Atopic (allergic) asthma is the most common disease of childhood and is strongly genetic in origin. Many genome-wide screens for asthma and its associated traits have now been carried out, and genetic linkage has been consistently identified in several regions. It is probable that these loci contain major genes influencing atopy and asthma. Candidate genes have already been identified from the cytokine cluster on chromosome 5 and the MHC on chromosome 6. These complex regions contain more than one susceptibility locus for allergic disease. Other regions do not contain obvious candidate genes, and positional cloning of these loci is likely to identify novel disease pathways. Parent-of-origin effects are prominent at some of the loci and some also show linkage to other inflammatory immune diseases. Several single gene disorders are associated with allergic disease and on occasion are also linked to the same chromosomal regions. The positional cloning of asthma genes is now feasible.
  • Journal article
    Lonjou C, Barnes K, Chen H, Cookson WOCM, Deichmann KA, Hall IP, Holloway JW, Laitinen T, Palmer LJ, Wjst M, Morton NEet al., 2000,

    A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG)

    , Proceedings of the National Academy of Sciences of the United States of America, Vol: 97, Pages: 10942-10947, ISSN: 0027-8424

    The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology.
  • Journal article
    Cota E, Hamill SJ, Fowler SB, Clarke Jet al., 2000,

    Two proteins with the same structure respond very differently to mutation: The role of plasticity in protein stability

    , JOURNAL OF MOLECULAR BIOLOGY, Vol: 302, Pages: 713-725, ISSN: 0022-2836
    • Cite
    • Citations: 66
  • Journal article
    Palmer LJ, Cookson WO, 2000,

    Genomic approaches to understanding asthma.

    , Genome Res, Vol: 10, Pages: 1280-1287, ISSN: 1088-9051

    Asthma is the most common chronic childhood disease in developed nations, and it is a complex disease that has high social and economic costs. Asthma and its associated intermediate phenotypes are under a substantial degree of genetic control. The genetic aetiology of asthma offers a means of better understanding its pathogenesis and, thus, improving preventive strategies, diagnostic tools, and therapies. Considerable effort and expense have been expended in attempts to detect genetic loci contributing to asthma susceptibility, and extensive candidate gene studies and a number of whole-genome screens have been undertaken. This article reviews the current state of knowledge of the genetics of asthma, with a focus on genomic approaches to understanding allergic diseases.
  • Journal article
    Ito K, Barnes PJ, Adcock IM, 2000,

    Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1β-induced histone H4 acetylation on lysines 8 and 12

    , MOLECULAR AND CELLULAR BIOLOGY, Vol: 20, Pages: 6891-6903, ISSN: 0270-7306
    • Cite
    • Citations: 563
  • Journal article
    Byrne B, Abramson J, Jansson M, Holmgren E, Iwata Set al., 2000,

    Fusion protein approach to improve the crystal quality of cytochrome <i>bo</i><sub>3</sub> ubiquinol oxidase from <i>Escherichia coli</i>

    , BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Vol: 1459, Pages: 449-455, ISSN: 0005-2728
  • Journal article
    Fisher MC, Koenig G, White TJ, Taylor JWet al., 2000,

    A test for concordance between the multilocus genealogies of genes and microsatellites in the pathogenic fungus <i>Coccidioides immitis</i>

    , MOLECULAR BIOLOGY AND EVOLUTION, Vol: 17, Pages: 1164-1174, ISSN: 0737-4038
  • Journal article
    Abramson J, Larsson G, Byrne B, Puustinen A, Garcia-Horsman A, Iwata Set al., 2000,

    Purification, crystallization and preliminary crystallographic studies of an integral membrane protein, cytochrome <i>bo</i><sub>3</sub> ubiquinol oxidase from <i>Escherichia coli</i>

    , ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, Vol: 56, Pages: 1076-1078, ISSN: 2059-7983
    • Cite
    • Citations: 11
  • Journal article
    Abecasis GR, Cookson WO, Cardon LR, 2000,

    Pedigree tests of transmission disequilibrium.

    , Eur J Hum Genet, Vol: 8, Pages: 545-551, ISSN: 1018-4813

    High-resolution mapping is essential for the positional cloning of complex disease genes. In outbred populations, linkage disequilibrium is expected to extend for short distances and could provide a powerful fine-mapping tool. Current family-based association tests use nuclear family members to define allelic transmission and controls, but ignore other types of relatives. Here we construct a general approach for scoring allelic transmission that accommodates families of any size and uses all available genotypic information. Family data allows for the construction of an expected genotype for every non-founder, and orthogonal deviates from this expectation are a measure of allelic transmission. These allelic transmission scores can be used to extend previously described tests of linkage disequilibrium for dichotomous or quantitative traits. Some of these tests are illustrated, together with a permutation framework for estimating exact significance levels. Simulation studies are used to investigate power and error rates of the approach. As a practical application, the method is used to investigate the relationship between circulating angiotensin-1 converting enzyme (ACE) levels and polymorphisms in the ACE gene using previously published data.

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