Introduction .................................................................................................... 1
1 History of Human Genetics ............................................................. 13
Arno G. Motulsky
2 Human Genome Sequence and Variation .................................... 31
Stylianos E. Antonarakis
3 Chromosomes................................................................................... 55
Michael R. Speicher
4 From Genes to Genomics to Proteomics ...................................... 139
Michael R. Speicher
5 Formal Genetics of Humans: Modes of Inheritance .................... 165
Arno G. Motulsky
6 Linkage Analysis for Monogenic Traits......................................... 211
Arno G. Motulsky and Michael Dean
7 Oligogenic Disease .......................................................................... 243
Jon F. Robinson and Nicholas Katsanis
8 Formal Genetics of Humans: Multifactorial Inheritance
and Common Diseases .................................................................... 263
Andrew G. Clark
8.1 Lessons from the Genome-Wide Association Studies
for Complex Multifactorial Disorders and Traits ......................... 287
Jacques S. Beckmann and Stylianos E. Antonarakis
9 Epigenetics ....................................................................................... 299
Bernhard Horsthemke
10 Human Gene Mutation: Mechanisms
and Consequences ........................................................................... 319
Stylianos E. Antonarakis and David N. Cooper
11 Human Hemoglobin ........................................................................ 365
George P. Patrinos and Stylianos E. Antonarakis
Contents Overview
xii Contents Overview
12 Human Genetics of Infectious Diseases ........................................ 403
Alexandre Alcaïs, Laurent Abel, and Jean-Laurent Casanova
13 Gene Action: Developmental Genetics ......................................... 417
Stefan Mundlos
14 Cancer Genetics ................................................................................ 451
Ian Tomlinson
15 The Role of the Epigenome in Human Cancers ............................ 471
Romulo Martin Brena and Joseph F. Costello
16 Population Genetic Principles and Human Populations ............ 487
Emmanouil T. Dermitzakis
17 Consanguinity, Genetic Drift, and Genetic Diseases
in Populations with Reduced Numbers of Founders .................. 507
Alan H. Bittles
18 Human Evolution ............................................................................. 529
Michael Hofreiter
19 Comparative Genomics ................................................................... 557
Ross C. Hardison
20 Genetics and Genomics of Human Population Structure .......... 589
Sohini Ramachandran, Hua Tang, Ryan N. Gutenkunst,
and Carlos D. Bustamante
21 Genetic Epidemiology ..................................................................... 617
Sophia S. Wang , Terri H. Beaty, and Muin J. Khoury
22 Pharmacogenetics ........................................................................... 635
Nicole M. Walley, Paola Nicoletti, and David B. Goldstein
23 Behavioral Genetics ......................................................................... 649
23.1 The Genetics of Personality ............................................................ 651
Jonathan Flint and Saffron Willis-Owen
23.2 Mental Retardation and Intellectual Disability ........................... 663
David L. Nelson
23.3 Genetic Factors in Alzheimer Disease and Dementia ................. 681
Thomas D. Bird
23.4 Genetics of Autism ........................................................................... 699
Brett S. Abrahams and Daniel H. Geschwind
23.5 The Genetics of Alcoholism and Other Addictive Disorders ..... 715
David Goldman and Francesca Ducci
23.6 Behavioral Aspects of Chromosomal Variants ............................ 743
Michael R. Speicher
Contents xiii
23.7 Genetics of Schizophrenia and Bipolar Affective Disorder ....... 759
Markus M. Nöthen, Sven Cichon, Christine Schmael,
and Marcella Rietschel
24 Model Organisms for Human Disorders ....................................... 777
Michael R. Speicher
24.1 Mouse as a Model for Human Disease .......................................... 779
Antonio Baldini
24.2 Caenorhabditis elegans, A Simple Worm: Bridging
the Gap Between Traditional and Systems-Level Biology ......... 787
Morgan Tucker and Min Han
24.3 Drosophila as a Model for Human Disease ................................... 795
Ruth Johnson and Ross Cagan
24.4 Human Genetics and the Canine System ...................................... 813
Heidi G. Parker and Elaine A. Ostrander
24.5 Fish as a Model for Human Disease ............................................... 827
Siew Hong Lam and Zhiyuan Gong
25 Genetic Counseling and Prenatal Diagnosis ................................ 845
Tiemo Grimm and Klaus Zerres
26 Gene Therapy ................................................................................... 867
Vivian W. Choi and R. Jude Samulski
27 Cloning in Research and Treatment of Human
Genetic Disease ................................................................................ 875
Ian Wilmut, Jane Taylor, Paul de Sousa, Richard Anderson,
and Christopher Shaw
28 Genetic Medicine and Global Health ............................................ 885
David J. Weatherall
29 Genetic Databases ........................................................................... 903
Introductory Note by Stylianos E. Antonarakis
29.1 Databases and Genome Browsers ................................................. 905
Rachel A. Harte, Donna Karolchik, Robert M. Kuhn, W. James Kent,
and David Haussler
29.2 Ensembl Genome Browser .............................................................. 923
Xosé M. Fernández and Ewan Birney
29.3 Databases in Human and Medical Genetics ................................. 941
Roberta A. Pagon, Ada Hamosh, Johan den Dunnen,
Helen V. Firth, Donna R. Maglott, Stephen T. Sherry,
Michael Feolo, David Cooper, and Peter Stenson
Subject Index .................................................................................................. 961