"It will be the basic aim of this book," writes Peter J. Bridge, "to impart to the reader the fundamentals of how we start with laboratory results and end up with numbers representing genetic risks." This practical guide for both clinical and research geneticists explains how to calculate an individual's genetic risk based on information available from genetic testing and from family pedigrees. Bridge begins with the general theory of estimating genetic risks, then progresses through familial and isolated cases, both simple and complex. A major strength of the book lies in the wealth of worked examples provided throughout the text. The disorders are selected to be widely applicable or adaptable as needed.
New to this edition are sections on consanguinity, multipoint linkage analysis, nonparametric methods, homozygosity mapping, and physical mapping. Also new is a chapter on other DNA-based calculations, including sections on paternity, zygosity, family reconstructions, and quantification of mitochondrial mutations.
Author(s): Peter J. Bridge
Edition: 2
Publisher: johns Hopkins University Press
Year: 1997
Language: English
Pages: 256
Contents:
Acknowledgments xiii
Statement on Discrimination xv
Introduction xvii
1. General Introduction to the Estimation of Genetic Risks –Pg 1
1.1 Mendelian Risk – Pg 2
1.2 Risk Modified by Reproductive History
1.3 Risk Based on Phenotype –Pg 3
1.4 Risk Based on Genotype –Pg 3
1.5 Familial versus New Mutations –Pg 4
1.6 Meiotic versus Mitotic Mutations –Pg 4
1.7 Non-Mendelian Genetic Mechanisms –Pg 5
2. Bayesian Risk Calculations for X-Linked Recessive Disorders –Pg 11
2.1 Unaffected Sons –Pg 11
2.2 Daughters with Unaffected Grandsons –Pg 14
2.3 Which Branches of the Family May Be Used? –Pg 16
2.4 Negative Family History –Pg 18
3. The Incorporation of Females with Biochemical Test Results into Bayesian Calculations –Pg 37
3.1 Linearity of the Test Results –Pg 37
3.2 Column Ratios –Pg 39
3.3 Biochemical Tests on the Consultand Herself –Pg 40
3.4 Stating Conditional Probabilities in Words –Pg 40
3.5 Resolution of Conflicting Evidence–Pg 41
3.6 Noncarrier Ratios –Pg 43
3.7 Negative Family History –Pg 46
4. Pedigree Risks in Autosomal Conditions 51
4.1 Autosomal Dominant Inheritance –Pg 51
4.2 Autosomal Recessive Inheritance –Pg 60
4.3 The Hardy-Weinberg Law–Pg 65
4.4 Consanguinity –Pg 67
5. Introduction to DNA Polymorphism –Pg 75
5.1 Types of DNA Polymorphism –Pg 75
5.2 The Significance of Phase –Pg 79
5.3 Flanking Markers –Pg 84
6. Statistical Approaches to Gene Mapping –Pg 87
6.1 Lod Scores –Pg 87
6.2 Probabilities over Pedigrees –Pg 99
6.3 Multipoint Linkage Analysis –Pg 104
6.4 Nonparametric Methods –Pg 107
6.5 Autozygosity Mapping –Pg 108
6.6 Physical Mapping –Pg 109
6.7 Annotation –Pg 109
7. The Use of DNA Markers to Predict Genetic Risks –Pg 111
7.1 Single Markers in Familial Cases –Pg 111
7.2 Flanking Markers in Familial Cases –Pg 118
7.3 Single Markers and Potentially New Mutations 129
7.4 Flanking Markers and Potentially New Mutations –Pg 135
7.5 Direct Detection of Mutations –Pg 135
7.6 Uniparental Disomy –Pg 139
7.7 Genetic Heterogeneity –Pg 145
7.8 Linkage Disequilibrium and Haplotype Analysis–Pg 145
7.9 When Do Mutations Occur? –Pg 152
7.10 “Haploid” Risk Calculations –Pg 155
8. The Integration of RFLP Data with Non-DNA Parameters –Pg 158
8.1 Biochemical Test Results –Pg 158
8.2 Incomplete Penetrance and Age-at-Onset Corrections –Pg 166
8.3 Testing for Hereditary Predispositions to Cancer –Pg 170
9. Other DNA-Based Calculations –Pg 175
9.1 Paternity –Pg 175
9.2 Zygosity –Pg 181
Appendix –Pg 185
Glossary –Pg 199
References –Pg 211
Index –Pg 217
