High-resolution SNP scan of chromosome 6p21 in pooled samples from patients with complex diseases |
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| Authors: | Herbon Nicole Werner Monika Braig Christine Gohlke Henning Dütsch Gaby Illig Thomas Altmüller Janine Hampe Jochen Lantermann Annette Schreiber Stefan Bonifacio Ezio Ziegler Annette Schwab Sibylle Wildenauer Dieter van den Boom Dirk Braun Andreas Knapp Michael Reitmeir Peter Wjst Matthias |
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| Institution: | 1. Institut für Epidemiologie, GSF Forschungszentrum für Umwelt und Gesundheit, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany;2. Klinik für Allgemeine Innere Medizin der Christian Albrechts Universität, FG Mukosaimmunologie, Schittenhelmstr. 12, 24105 Kiel, Germany;3. Institut für Diabetesforschung, Städtisches Krankenhaus Schwabing, Kölner Platz 1, 80804 München, Germany;4. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany;5. Sequenom Inc., 3595 John Hopkins Court, San Diego, CA 92121-1331, USA;6. Institut für Medizinische Biometrie, Informatik und Epidemiologie, Universitätsklinikum Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany;7. Institut für Gesundheitsökonomie und Management im Gesundheitswesen, GSF Forschungszentrum für Umwelt und Gesundheit,Ingolstädter Landstr. 1, 85764 Neuherberg, Germany;8. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-Maximilians-Universität München,Marchioninistr. 15, 81377 München, Germany;1. Department of Chemistry, Yasouj University, Yasouj 7591874831, Iran;2. Departamento de Quimica Inorganica, Universidade de Vigo, E-36200 Vigo, Galicia, Spain;3. Department of Chemistry and Food Chemistry, Technische Universität Dresden, 01062 Dresden, Germany;1. Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany;2. Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany;1. Department of Biology, Jan Evangelista Purkinje University, Usti nad Labem, Czech Republic;2. Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland;3. Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany;1. Institute for Computational Mathematics, Technische Universität Braunschweig, Pockelsstraße 14, 38106 Braunschweig, Germany;2. TU Dresden, Fachrichtung Mathematik, Institut für Analysis, Helmholtzstraße 10, 01069 Dresden, Germany;1. Materials Science Centre, Indian Institute of Technology, Kharagpur 721302, India;2. Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Strasse. 6, 01069 Dresden, Germany;1. School of Automotive Studies, Tongji University, 4800 Cao''an Road, 201804 Shanghai, PR China;2. Wilhelm-Ostwald-Institut für Physikalische und Theoretische Chemie, Universität Leipzig, Linnéstraβe 2, 04103 Leipzig, Germany |
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| Abstract: | We apply a high-throughput protocol of chip-based mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight; MALDI-TOF) as a method of screening for differences in single-nucleotide polymorphism (SNP) allele frequencies. Using pooled DNA from individuals with asthma, Crohn's disease (CD), schizophrenia, type 1 diabetes (T1D), and controls, we selected 534 SNPs from an initial set of 1435 SNPs spanning a 25-Mb region on chromosome 6p21. The standard deviations of measurements of time of flight at different dots, from different PCRs, and from different pools indicate reliable results on each analysis step. In 90% of the disease-control comparisons we found allelic differences of <10%. Of the T1D samples, which served as a positive control, 10 SNPs with significant differences were observed after taking into account multiple testing. Of these 10 SNPs, 5 are located between DQB1 and DRB1, confirming the known association with the DR3 and DR4 haplotypes whereas two additional SNPs also reproduced known associations of T1D with DOB and LTA. In the CD pool also, two earlier described associations were found with SNPs close to DRB1 and MICA. Additional associations were found in the schizophrenia and asthma pools. They should be confirmed in individual samples or can be used to develop further quality criteria for accepting true differences between pools. The determination of SNP allele frequencies in pooled DNA appears to be of value in assigning further genotyping priorities also in large linkage regions. |
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