Second Edition features the latest tools for uncovering thegenetic basis of human disease The Second Edition of this landmark publication bringstogether a team of leading experts in the field to thoroughlyupdate the publication. Readers will discover the tremendousadvances made in human genetics in the seven years that haveelapsed since the First Edition. Once again, the editorshave assembled a comprehensive introduction to the strategies,designs, and methods of analysis for the discovery of genes incommon and genetically complex traits. The growing social, legal,and ethical issues surrounding the field are thoroughly examined aswell. Rather than focusing on technical details or particularmethodologies, the editors take a broader approach that emphasizesconcepts and experimental design. Readers familiar with theFirst Edition will find new and cutting-edge materialincorporated into the text: * Updated presentations of bioinformatics, multiple comparisons,sample size requirements, parametric linkage analysis, case-controland family-based approaches, and genomic screening * New methods for analysis of gene-gene and gene-environmentinteractions * A completely rewritten and updated chapter on determininggenetic components of disease * New chapters covering molecular genomic approaches such asmicroarray and SAGE analyses using single nucleotide polymorphism(SNP) and cDNA expression data, as well as quantitative trait loci(QTL) mapping The editors, two of the world's leading genetic epidemiologists,have ensured that each chapter adheres to a consistent and highstandard. Each one includes all-new discussion questions andpractical examples. Chapter summaries highlight key points, and alist of references for each chapter opens the door to furtherinvestigation of specific topics. Molecular biologists, human geneticists, geneticepidemiologists, and clinical and pharmaceutical researchers willfind the Second Edition a helpful guide to understanding thegenetic basis of human disease, with its new tools for detectingrisk factors and discovering treatment strategies.
Autorentext
JONATHAN L. HAINES is Director of the Program in Human Genetics, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine. His research into the localization and identification of genes involved in human disease includes studying Alzheimer's disease, multiple sclerosis, Parkinson's disease, autism, macular degeneration, and other complex diseases.
MARGARET A. PERICAK-VANCE is Director of the Center for Human Genetics and Chief of the Section of Medical Genetics in the Department of Medicine, Duke University School of Medicine. She is a founding Fellow of the American College of Medical Genetics. Her research interests include the integration of genomic and statistical technologies and their application to diseases of importance to public health, with an emphasis on neurologic diseases.
Klappentext
Second Edition features the latest tools for uncovering the genetic basis of human disease
The Second Edition of this landmark publication brings together a team of leading experts in the field to thoroughly update the publication. Readers will discover the tremendous advances made in human genetics in the seven years that have elapsed since the First Edition. Once again, the editors have assembled a comprehensive introduction to the strategies, designs, and methods of analysis for the discovery of genes in common and genetically complex traits. The growing social, legal, and ethical issues surrounding the field are thoroughly examined as well.
Rather than focusing on technical details or particular methodologies, the editors take a broader approach that emphasizes concepts and experimental design. Readers familiar with the First Edition will find new and cutting-edge material incorporated into the text:
- Updated presentations of bioinformatics, multiple comparisons, sample size requirements, parametric linkage analysis, case-control and family-based approaches, and genomic screening
- New methods for analysis of gene-gene and gene-environment interactions
- A completely rewritten and updated chapter on determining genetic components of disease
- New chapters covering molecular genomic approaches such as microarray and SAGE analyses using single nucleotide polymorphism (SNP) and cDNA expression data, as well as quantitative trait loci (QTL) mapping
The editors, two of the world's leading genetic epidemiologists, have ensured that each chapter adheres to a consistent and high standard. Each one includes all-new discussion questions and practical examples. Chapter summaries highlight key points, and a list of references for each chapter opens the door to further investigation of specific topics.
Molecular biologists, human geneticists, genetic epidemiologists, and clinical and pharmaceutical researchers will find the Second Edition a helpful guide to understanding the genetic basis of human disease, with its new tools for detecting risk factors and discovering treatment strategies.
Inhalt
Foreword.
Preface.
Contributors.
1. Basic Concepts in Genetics and Linkage Analysis (Elizabeth C. Melvin and Marcy C. Speer).
Introduction.
Historical Contributions.
Segregation and Linkage Analysis.
HardyWeinberg Equilibrium.
DNA, Genes, and Chromosomes.
Structure of DNA.
Genes and Alleles.
Genes and Chromosomes.
Inheritance Patterns in Mendelian Disease.
Genetic Changes Associated with Disease/Trait Phenotypes.
Point Mutations.
Deletion/Insertion Mutations/
Novel Mechanisms of Mutation: Unstable DNA and Trinucleotide Repeats.
Susceptibility Versus Causative Genes.
Genes, Mitosis, and Meiosis.
When Genes and Chromosomes Segregate Abnormally.
Ordering and Spacing of Loci by Mapping Techniques.
Physical Mapping.
Genetic Mapping.
Interference and Genetic Mapping.
Meiotic Breakpoint Mapping.
Disease Gene Discovery.
Information Content in a Pedigree.
Disease Gene Localization.
Extensions to Complex Disease.
Summary.
References.
2. Defining Disease Phenotypes (Arthur S. Aylsworth).
Introduction.
Exceptions to Traditional Mendelian Inheritance Patterns.
Pseudodominant Transmission of a Recessive.
Pseudorecessive Transmission of a Dominant.
Mosaicism.
Mitochondrial Inheritance.
Incomplete Penetrance and Variable Expressivity.
Genomic Imprinting.
Phenocopies and Other Environmentally Related Effects.
Heterogeneity.
Genetic Heterogeneity.
Phenotypic Heterogeneity.
Complex Inheritance.
Polygenic and Multifactorial Models.
Role of Environment.
Role of Chance in Phenotype Expression.
Phenotype Definition.
Classification of Disease.
Nonsyndromic Phenotypes.
Syndromic Phenotypes.
Associations and Syndromes of Unknown Cause.
Importance of Chromosomal Rearrangements in Mapping.
Qualitative (Discontinuous) and Quantitative (Continuous) Traits.
Defining Phenotypes for Analysis of Complex Genetic Disorders.
Select Most Biologically Meaningful Phenotype.
Partition Phenotype or Dataset by Cause and Associated Pathology.
Summary: Approach to Phenotype Definition.
Resources for Information about Clinical Genetics and Phenotype Definition.
References.
3. Determining Genetic Component of a Disease (Allison Ashley-Koch).
Introduction .
Study Design .
Selecting a Study Population .
Ascertainment.
Approaches to Determining the Genetic Component of a Disease.
Cosegregation with Chromosomal A…