Genes and common diseases

Section 1: Introductory Principles 1 Genes and their expression 3 Dirk-Jan Kleinjan 2 Epigenetic modification of chromatin 20 Donncha Dunican, Sari Pennings and Richard Meehan 3 Population genetics and disease 44 Donald F. Conrad and Jonathan K. Pritchard 4 Mapping common disease genes 59 Naomi R. Wray and Peter M. Visscher 5 Population diversity, genomes and disease 80 Gianpiero L. Cavalleri and David B. Goldstein 6 Study design in mapping complex disease traits 92 Harry Campbell and Igor Rudan 7 Diseases of protein misfolding 113 Christopher M. Dobson 8 Aging and disease 132 Thomas T. Perls 9 The MHC paradigm: genetic variation and complex disease 142 Adrian P. Kelly and John Trowsdale v 10 Lessons from single gene disorders 152 Nicholas D. Hastie 11 Environment and disease 164 A. J. McMichael and K. B. G. Dear 12 Contemporary ethico-legal issues in genetics 176 Renate Gertz, Shawn Harmon and Geoffrey Pradella Section 2: Common Medical Disorders 13 Developmental disorders 201 Stephen P. Robertson and Andrew O. M. Wilkie 14 Genes, environment and cancer 213 D. Timothy Bishop 15 The polygenic basis of breast cancer 224 Paul D. P. Pharoah and Bruce A. J. Ponder 16 TP53: A master gene in normal and tumor suppression 233 Pierre Hainaut 17 Genetics of colorectal cancer 245 Susan M. Farrington and Malcolm G. Dunlop 18 Genetics of autoimmune disease 268 John I. Bell and Lars Fugger 19 Susceptibility to infectious diseases 277 Andrew J. Walley and Adrian V. S. Hill 20 Inflammatory bowel diseases 302 Jean-Pierre Hugot 21 Genetic anemias 316 W. G. Wood and D. R. Higgs 22 Genetics of chronic disease: obesity 328 I. Sadaf Farooqi and Stephen O’Rahilly 23 Type 2 diabetes mellitus 344 Mark I. McCarthy 24 Genetics of coronary heart disease 359 Rossi Naoumova, Stuart A. Cook, Paul Cook and Timothy J. Aitman 25 Genetics of hypertension 377 B. Keavney and M. Lathrop 26 Obstructive pulmonary disease 391 Bipen D. Patel and David A. Lomas 27 Skeletal disorders 406 Robert A. Colbert 28 The genetics of common skin diseases 427 Jonathan Rees 29 Molecular genetics of Alzheimer’s disease and other adult-onset dementias 439 P. H. St George-Hyslop 30 Major psychiatric disorders in adult life 454 Amanda Elkin, Sridevi Kalidindi, Kopal Tandon and Peter McGuffin 31 Speech and language disorders 469 Gabrielle Barnby and Anthony J. Monaco 32 Common forms of visual handicap 488 Alan Wright 33 Genetic and environmental influences on hearing impairment 505 Karen P. Steel 34 Pharmacogenomics: clinical applications 516 Gillian Smith, Mark Chamberlain and C. Roland Wolf Index 529 vi Contents