Medical Genetics at a Glance

Preface to the first edition 7 Preface to the third edition 7 Acknowledgements 8 List of abbreviations 9 Part 1 Overview 1 The place of genetics in medicine 12 Part 2 The Mendelian approach 2 Pedigree drawing 14 3 Mendel's laws 16 4 Principles of autosomal dominant inheritance and pharmacogenetics 19 5 Autosomal dominant inheritance, clinical examples 22 6 Autosomal recessive inheritance, principles 25 7 Consanguinity and major disabling autosomal recessive conditions 28 8 Autosomal recessive inheritance, life-threatening conditions 31 9 Aspects of dominance 34 10 X-linked and Y-linked inheritance 36 11 X-linked inheritance, clinical examples 38 12 Mitochondrial inheritance 40 13 Risk assessment in Mendelian conditions 42 Part 3 Basic cell biology 14 The cell 44 15 The chromosomes 46 16 The cell cycle 48 17 Biochemistry of the cell cycle 50 18 Gametogenesis 52 Part 4 Basic molecular biology 19 DNA structure 54 20 DNA replication 56 21 The structure of genes 58 22 Production of messenger RNA 60 23 Non-coding RNA 62 24 Protein synthesis 64 Part 5 Genetic variation 25 Types of genetic alterations 66 26 Mutagenesis and DNA repair 68 27 Genomic imprinting 70 28 Dynamic mutation 73 29 Normal polymorphism 76 30 Allele frequency 79 Part 6 Organization of the human genome 31 Genetic linkage and genetic association 82 32 Physical gene mapping 84 33 Gene identifi cation 86 34 Clinical application of linkage and association 88 Part 7 Cytogenetics 35 Chromosome analysis 90 36 Autosomal aneuploidies 92 37 Sex chromosome aneuploidies 94 38 Chromosome structural abnormalities 96 39 Chromosome structural abnormalities, clinical examples 98 40 Contiguous-gene and single-gene syndromes 102 Part 8 Embryology and congenital abnormalities 41 Human embryology in outline 106 42 Body patterning 108 43 Sexual differentiation 110 44 Abnormalities of sex determination 112 45 Congenital abnormalities, pre-embryonic, embryonic and of intrinsic causation 114 46 Congenital abnormalities arising at the fetal stage 117 47 Development of the heart 120 48 Cardiac abnormalities 122 49 Facial development and dysmorphology 124 Part 9 Multifactorial inheritance and twin studies 50 Principles of multifactorial disease 127 51 Multifactorial disease in children 130 52 Common disorders of adult life 133 53 Twin studies 136 Part 10 Cancer 54 The signal transduction cascade 138 55 The eight hallmarks of cancer 140 56 Familial cancers 142 57 Genomic approaches to cancer management 144 Part 11 Biochemical genetics 58 Disorders of amino acid metabolism 146 59 Disorders of carbohydrate metabolism 149 60 Metal transport, lipid metabolism and amino acid catabolism defects 152 61 Disorders of porphyrin and purine metabolism and the urea/ornithine cycle 156 62 Lysosomal, glycogen storage and peroxisomal diseases 160 63 Biochemical diagnosis 165 Part 12 Immunogenetics 64 Immunogenetics, cellular and molecular aspects 168 65 Genetic disorders of the immune system 170 66 Autoimmunity, HLA and transplantation 173 Part 13 Molecular diagnosis 67 DNA hybridization-based analysis systems 176 68 DNA sequencing 179 69 The polymerase chain reaction 182 70 DNA profiling 184 Part 14 Genetic counselling, disease management, ethical and social issues 71 Reproductive genetic counselling 186 72 Prenatal sampling 188 73 Avoidance and prevention of disease 191 74 Management of genetic disease 194 75 Ethical and social issues in clinical genetics 197 Self-assessment case studies: questions 200 Self-assessment case studies: answers 205 Glossary 214 Appendix 1: the human karyotype 219 Appendix 2: information sources and resources 220 Index 222