Essential Medical Genetics, Includes Desktop Edition

Edward S. Tobias, Professor of Genetic Medicine, University of Glasgow, and Honorary Consultant in Medical Genetics, West of Scotland Regional Genetics Service, Institute of Medical Genetics, Glasgow. Medical Genetics undergraduate Teaching Lead, Clinical Director, MSc in Medical Genetics, and Fellow of the Higher Education Authority.Dr Tobias won the Best College Teacher Award at Glasgow University in March 2013, as chosen by the Student Representative Council and the students themselves.He also won the Teaching Excellence Award 2012 from the University's Principal and Senate Committee.Glasgow University came top in the UK National Student Survey 2012 for Genetics teaching.Michael Connor, Professor of Medical Genetics, University of Glasgow, and Director of the West of Scotland Regional Genetics Service, Institute of Medical Genetics, Yorkhill, Glasgow.Malcolm Ferguson-Smith, Emeritus Professor of Pathology, University of Cambridge and formerly Director of the East Anglia Regional Genetics Service, Addenbrooke's Hospital, Cambridge.

• Preface viiAcknowledgements ixHow to get the best out of your textbook xPart 1: Basic principles 11 Medical genetics in perspective 3Scientific basis of medical genetics 5Clinical applications of medical genetics 92 The human genome 13Structure and organisation of the genome 14Gene identification 14The Human Genome Project 143 Nucleic acid structure and function 23Nucleic acid structure 24Nucleic acid function 26Gene regulation 29DNA replication 31Mutation types, effects and nomenclature 324 DNA analysis 41Basic methods 42Mutation detection 43Indirect mutant gene tracking 52Analysis of DNA length polymorphisms 53Analysis of single-nucleotide polymorphisms 545 Chromosomes 57Chromosome structure 58Chromosome analysis 59Chromosome heteromorphisms 65Chromosomes in other species 66Mitochondrial chromosomes 68Mitosis 696 Gametogenesis 73Meiosis 74Spermatogenesis 76Oogenesis 78Fertilisation 78X-inactivation and dosage compensation 79Sex chromosome aberrations 80Sex determination and differentiation 83Genomic imprinting (parental imprinting) 837 Chromosome aberrations 89Numerical aberrations 90Structural aberrations 92Cytogenetic and molecular methods for the detection of chromosomal aberrations 100Identification of the chromosomal origin of complex structural rearrangements 107Other aberrations 1118 Typical Mendelian inheritance 117Introduction to autosomal single-gene inheritance 118Autosomal dominant inheritance 118Autosomal recessive inheritance 120Introduction to sex-linked inheritance 123X-linked recessive inheritance 125X-linked dominant inheritance 127Y-linked inheritance (holandric inheritance) 1289 Atypical Mendelian inheritance 131Genetic anticipation 132Pseudoautosomal inheritance 134Autosomal dominant inheritance with sex limitation 134Pseudodominant inheritance 134X-linked dominant inheritance with male lethality 135Mosaicism 135Modifier genes and digenic inheritance 135Uniparental disomy 136Imprinting disorders 13610 Non-Mendelian inheritance 141Multifactorial disorders 142Somatic cell genetic disorders 147Mitochondrial disorders 14711 Medical genetics in populations 151Selection for single-gene disorders 152Founder effect and genetic drift for single-gene disorders 153Altered mutation rate for single-gene disorders 154Linkage analysis and the International Hapmap Project 154Human population evolution and migration 155Part 2: Clinical applications 16112 Genetic assessment, genetic counselling and reproductive options 163Communication of advice 164Special points in counselling 168Prenatal diagnosis 170Amniocentesis 170Chorionic villus sampling 174Cordocentesis, fetal skin biopsy and fetal liver biopsy 175Ultrasonography 175Fetal cells in the maternal circulation 175Free fetal DNA and RNA detection 175Preimplantation genetic diagnosis 17613 Family history of cancer 179General principles 180Tumour suppressor genes 181Genes involved in DNA repair mechanisms 187Oncogenes 187Other cancer-related genes 189Genetic counselling aspects of cancer 189Common familial cancer predisposition syndromes 18914 Family history of common adult-onset disorder 199General principles 200Diabetes mellitus: common and monogenic forms 200Dementia: Alzheimer disease, Huntington disease, prion diseases and other causes 20215 Strong family history – typical Mendelian disease 209Cystic fibrosis 210Duchenne and Becker muscular dystrophies 212Neurofibromatosis type 1 21416 Strong family history – other inheritance mechanisms 219Myotonic dystrophy 220Fragile X syndrome 221Mitochondrial disorder 222Imprinting-related disorder 223Chromosomal translocation 22417 Screening for disease and for carriers 229Prenatal screening 230Neonatal screening 233Carrier detection in the adult population 234Presymptomatic screening of adults 23718 Family history of one or more congenital malformations 241Aetiology 242Chromosomal disorders 243Neural tube defects 247Teratogenic effects 250Multiple malformation syndromes 253Part 3: Electronic databases – a user’s guide 26519 Electronic databases – a user’s guide 267Finding information regarding specific conditions and names of associated genes 268Laboratories undertaking genetic testing 270Patient information and support groups 270Gene- and protein-specific sequence, structure, function and expression information 272Nucleotide sequences and human mutations 281Automatic primer design tools 281Displaying map data for genes and markers 287Online missense mutation analysis tools 288Computer-aided syndrome diagnosis 293Professional genetics societies 297The Human Genome Project: ethics and education 297Self-assessment – answers 305Appendix 1: Odds, probabilities and applications of Bayes’ theorem 312Appendix 2: Calculation of the coefficients of relationship and inbreeding 314Appendix 3: Population genetics of single-gene disorders 315Appendix 4: Legal aspects 317Glossary 318Index 324

"Essential Medical Genetics is the perfect resource for a course on medical genetics, and is now accompanied by a regularly updated website and the FREE enhanced Wiley Desktop Edition (upon purchase of the book)." (MedReport, 9 October 2012)"I have watched this textbook from its first inception and was disappointed that there was no new edition for so many years. Having waited, the result now is excellent and it has overcome my preference for Emery's Elements as a basic human genetics text."—Emeritus Professor in Clinical Genetics"I find the reference to electronic resources particularly useful, especially for people who approach clinical genetics for the first time and are not familiar with these tools." —Dr Sixto García-Miñaúr, Imperial College London, and Hospital Universitario La Paz, Madrid, SpainReviews of the previous edition"This book is an easy to read, well illustrated introduction to medical genetics. It deals nicely with all the classical aspects of the subject..."—Black Bag, Medical Students' Society of Bristol University"...a justifiably popular introductory text."—The British Medical Journal