Medical Genetics at a Glance

Dorian J. Pritchard is former lecturer in Human Genetics, University of Newcastle-upon-Tyne, UK and former Visiting Lecturer in Medical Genetics, International Medical University, Kuala Lumpur, Malaysia. Bruce Korf is Wayne H. and Sara Crews Finley Chair in Medical Genetics, Professor and Chair, Department of Genetics, and Director of the Heflin Center for Genomic Sciences at the University of Alabama at Birmingham, USA.

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