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  • Journal article
    Cota E, Steward A, Fowler SB, Clarke Jet al., 2001,

    The folding nucleus of a fibronectin type III domain is composed of core residues of the immunoglobulin-like fold

    , JOURNAL OF MOLECULAR BIOLOGY, Vol: 305, Pages: 1185-1194, ISSN: 0022-2836
  • Journal article
    Abecasis GR, Noguchi E, Heinzmann A, Traherne JA, Bhattacharyya S, Leaves NI, Anderson GG, Zhang Y, Lench NJ, Carey A, Cardon LR, Moffatt MF, Cookson WOCet al., 2001,

    Extent and Distribution of Linkage Disequilibrium in Three Genomic Regions.

    , American Journal of Human Genetics, Vol: 68, Pages: 191-197, ISSN: 0002-9297

    The positional cloning of genes underlying common complex diseases relies on the identification of linkage disequilibrium (LD) between genetic markers and disease. We have examined 127 polymorphisms in three genomic regions in a sample of 575 chromosomes from unrelated individuals of British ancestry. To establish phase, 800 individuals were genotyped in 160 families. The fine structure of LD was found to be highly irregular. Forty-five percent of the variation in disequilibrium measures could be explained by physical distance. Additional factors, such as allele frequency, type of polymorphism, and genomic location, explained <5% of the variation. Nevertheless, disequilibrium was occasionally detectable at 500 kb and was present for over one-half of marker pairs separated by <50 kb. Although these findings are encouraging for the prospects of a genomewide LD map, they suggest caution in interpreting localization due to allelic association.

  • Journal article
    Abramson J, Svensson-Ek M, Byrne B, Iwata Set al., 2001,

    Structure of cytochrome <i>c</i> oxidase:: a comparison of the bacterial and mitochondrial enzymes

    , BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, Vol: 1544, Pages: 1-9, ISSN: 0167-4838
  • Conference paper
    Cherny SS, Abecasis GR, Cookson WOC, Sham PC, Cardon LRet al., 2001,

    The effect of genotype and pedigree error on linkage analysis: Analysis of three asthma genome scans

    , Pages: S117-S122, ISSN: 0741-0395

    The effects of genotype and relationship errors on linkage results are evaluated in three of the Genetic Analysis Workshop 12 asthma genome scans. A number of errors are detected in the samples. While the evidence for linkage is not striking in any data set with or without error, in some cases the difference in test statistic could support different conclusions. The results provide empirical evidence for the predicted effects of genotype and relationship error and highlight the need for rigorous detection and elimination of data error in complex trait studies. © 2001 Wiley-Liss, Inc.

  • Conference paper
    Cookson WOCM, Abeçasis GR, 2001,

    Oxford genome screen for asthma-associated traits

    , Pages: S1-S3, ISSN: 0741-0395

    A genome screen for linkage of quantitative traits underlying asthma has been carried out previously by our group on 80 families sub-selected for discordant phenotypes from a general population sample. The families contained a total of 203 offspring forming 172 sib-pairs. Genotypic data for at a total of 296 markers were available. This paper describes the ascertainment, phenotypic data, and genotypic data made available for Genetic Analysis Workshop 12. © 2001 Wiley-Liss, Inc.

  • Conference paper
    Palmer LJ, Cookson WOCM, Deichmann KA, Holloway JW, Laitinen Tet al., 2001,

    Single region linkage analyses of asthma: Description of data sets

    , Pages: S9-S15, ISSN: 0741-0395

    Linkage (genotypic) data from the 5q31-33 candidate region for asthma were contributed to Genetic Analysis Workshop 12 by members of the International Consortium on Asthma Genetics (COAG). Data came from five independent studies sampled from five countries. Genotypic data for a total of 26 markers were available, although the number of markers typed in each data set varied. Phenotypic and genotypic data was available from a total of 569 families and 3,175 subjects. The phenotypic data available varied among the studies; however information regarding physician-diagnosed asthma and total serum IgE levels was available in all five studies. This paper describes the ascertainment, data collection methods, phenotypic data, and genotypic data available for the single linkage region analyses undertaken for Genetic Analysis Workshop 12. © 2001 Wiley-Liss, Inc.

  • Conference paper
    Abecasis GR, Cardon LR, Cookson WOC, Sham PC, Cherny SSet al., 2001,

    Association analysis in a variance components framework

    , Pages: S341-S346, ISSN: 0741-0395

    Association analyses conducted in a variance components framework can include information from all available individuals but remain unbiased in the presence of familiality or linkage. Models that include both linkage and association parameters provide different estimates of the effect of a single locus and can be used to distinguish causal polymorphisms from other types of variation. We examine some of these models and their properties in a blind analysis of the simulated Genetic Analysis Workshop 12 data sets. © 2001 Wiley-Liss, Inc.

  • Journal article
    Denison SH, Negrete-Urtasun S, Mingot JM, Tilburn J, Mayer WA, Goel A, Espeso EA, Peñalva MA, Arst HNet al., 2001,

    Putative membrane components of signal transduction pathways for ambient pH regulation in <i>Aspergillus</i> and meiosis in <i>Saccharomyces</i> are homologous (vol 30, pg 259, 1998)

    , MOLECULAR MICROBIOLOGY, Vol: 39, Pages: 211-211, ISSN: 0950-382X
  • Journal article
    Nicholas HB, Arst HN, Caddick MX, 2001,

    Evaluating low level sequence identities - Are <i>Aspergillus</i> QUTA and AROM homologous?

    , EUROPEAN JOURNAL OF BIOCHEMISTRY, Vol: 268, Pages: 414-419, ISSN: 0014-2956
  • Journal article
    Nicholas HB, Arst HN, Caddick MX, 2001,

    Evaluating low level sequence identities

    , European Journal of Biochemistry, Vol: 268, Pages: 414-419, ISSN: 0014-2956

    <jats:p>A review published several years ago [Hawkins, A.R. &amp; Lamb, H.K. (1995) <jats:italic>Eur. J. Biochem</jats:italic>. <jats:bold>232</jats:bold>, 7–18] proposed that genetic, biochemical and physiological data can override sequence comparison in the determination of homology in instances where structural information is unavailable. Their lead example was the hypothesis that the transcriptional activator protein for quinate catabolism in <jats:italic>Aspergillus nidulans</jats:italic>, QUTA, is derived from the pentafunctional AROM protein by a gene duplication followed by cleavage [Hawkins, A.R., Lamb, H.K., Moore, J.D. &amp; Roberts, C.F. (1993) <jats:italic>Gene</jats:italic><jats:bold>136</jats:bold>, 49–54]. We tested this hypothesis by a sensitive combination of position‐specific log‐odds scoring matrix methods. The position‐specific log‐odds scoring matrices were derived from a large number of 3‐dehydroquinate synthase and 5‐<jats:italic>enol</jats:italic>pyruvylshikimate‐3‐phosphate synthase domains that were proposed to be the domains from the AROM protein that gave rise to the transcriptional activator protein for quinate metabolism. We show that the degree and pattern of similarity between these position‐specific log‐odds scoring matrices and the transcriptional activator protein for quinate catabolism in <jats:italic>A. nidulans</jats:italic> is that expected for random sequences of the same composition. This level of similarity provides no support for the suggested gene duplication and cleavage. The lack of any trace of evidence for homology following a comprehensive sequence analysis indicates that the homology hypothesis is without foundation, underlining the necessity to accept only similarity of sequence and/or structure as evidence of evolutionary relatedness. Further, QUTA is homologous throughout its entire length

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