DNA Polymorphisms as Disease Markers

1. Front Matter

   Pages i-viii

   PDF

2. Theoretical Background

   1. Genetic Approaches to Common Diseases

      • Arno G. Motulsky

      Pages 1-4

   2. A Candidate Gene Approach to the Genetics of Normal Lipid Variation: DNA Association Studies and Genotype by Environment Interaction

      • Eric Boerwinkle, Lawrence Chan

      Pages 5-14

   3. Molecular Genetics Approach to Polygenic Disease—Initial Results from Atherosclerosis Research

      • Harald Funke, Arnold von Eckardstein, Gerd Assmann

      Pages 15-25

3. Diabetes

   1. Facilitative Glucose Transporters: Regulation and Possible Role in NIDDM

      • Mike Mueckler, Karen Tordjman

      Pages 27-41

   2. Molecular Genetic Approach to Polygenic Disease: Non-Insulin Dependent Diabetes Mellitus (NIDDM)

      • M. Alan Permutt, Laszlo Koranyi, Akira Matsutani

      Pages 43-59

4. Lipids

   1. HDL and Reverse Transport of Cholesterol: Insights from Mutants

      • Gerd Assmann, Arnold von Eckardstein, Harald Funke

      Pages 61-70

   2. Apolipoprotein E Polymorphisms and the Genetic Heterogeneity of Familial Dysbetalipoproteinemia

      • Louis M. Havekes, Arn M. J. M. van den Maagdenberg, Peter de Knijff, Monique Mulder, Rune R. Frants

      Pages 71-77

   3. Abnormalities of Apolipoprotein B Metabolism in the Lipid Clinic

      • Alberto Corsini, Alberico L. Catapano, Maria Mazzotti, Guido Franceschini, Cesare Romano, Remo Fumagalli et al.

      Pages 79-89

   4. Genetic Variation at the APOA-I, C-III, A-IV Gene Complex: A Critical Review of the Associations Between the PSTI and SSTI RFLPS at this Locus with Lipid Disorders

      • Jose M. Ordovas, Fernando Civeira, Carmen Garces, Miguel Pocovi

      Pages 91-103

   5. The Molecular Basis of the Chylomicronemia Syndrome

      • Detlev Ameis, Junji Kobayashi, Heiner Greten, Michael C. Schotz

      Pages 105-109

   6. Lipoprotein Lipase Gene Variants in Subjects with Hypertriglyceridaemia and Coronary Atherosclerosis

      • J. A. Thorn, D. J. Galton

      Pages 111-121

5. Atherosclerosis

   1. Atherosclerosis: The Genetic Analysis of a Multi-Factorial Disease

      • J. C. Chamberlain, D. J. Galton

      Pages 123-133

   2. RFLP Markers of Familial Coronary Heart Disease

      • William H. Price, Arthur H. Kitchin

      Pages 135-147

   3. DNA Polymorphisms as Disease Markers

      • David J. Galton, John C. Alcolado

      Pages 149-155

6. Back Matter

   Pages 157-160

   PDF

The purpose of this workshop was to assess the value of DNA polymorphisms for the prediction, diagnosis or elucidation of aetiology for common metabolic diseases such as diabetes, hyperlipidaemia and atherosclerosis. The advent of recombinant DNA techniques has produced an explosion in knowledge of restriction site polymorphisms and hypervariable sequences around candidate genes for such common metabolic diseases as atherosclerosis, hyperlipidaemia and diabetes mellitus. These diseases are the major causes of morbidity and mortality in Western societies today. Since 1983 it has become apparent that there is much more variation in the frequency and sites of these DNA polymorphisms in human populations than was initially appreciated and that the majority of these DNA polymorphisms are only linkage markers for the disease. Consequently it was considered timely for laboratories involved in the mapping of these DNA mutations to meet together to discuss the implications of their studies. The main issues are whether such DNA polymorphisms will lead to an identification of major aetiological loci and which are the best techniques to achieve this? What is the cause of the differences in frequencies of such polymorphisms amongst world populations? Are such studies best conducted in homogeneous populations or in pedigrees? Are haplotypes, though more laborious to construct, a better way to proceed than analysis of single site polymorphisms? What are the consensus polymorphic sites that relate to the common metabolic diseases of diabetes, atherosclerosis and the hyperlipidaemias? The real need now to discuss the theoretical background behind the

• DNA
• Lipid
• atherosclerosis
• coronary heart disease
• genes
• genetics
• heart
• heart disease
• high-density lipoprotein (HDL)
• lipoprotein
• metabolism
• molecular genetics
• mutation
• protein

• Department of Medicine, St. Bartholomew’s Hospital, London, UK

  D. J. Galton

• Zentrallaboratorien der Medizinische Einrichtungen, University of Munster, Germany

  G. Assmann

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