Genetic Theory and Analysis - Finding Meaning in a Genome

GENETIC THEORY AND ANALYSIS
 
Understand and apply what drives change of characteristic genetic traits and heredity
 
Genetics is the study of how traits are passed from parents to their offspring and how the variation in those traits affects the development and health of the organism. Investigating how these traits affect the organism involves a diverse set of approaches and tools, including genetic screens, DNA and RNA sequencing, mapping, and methods to understand the structure and function of proteins. Thus, there is a need for a textbook that provides a broad overview of these methods.
 
Genetic Theory and Analysis meets this need by describing key approaches and methods in genetic analysis through a historical lens. Focusing on the five basic principles underlying the field--mutation, complementation, recombination, segregation, and regulation--it identifies the full suite of tests and methodologies available to the geneticist in an age of flourishing genetic and genomic research. This second edition of the text has been updated to reflect recent advances and increase accessibility to advanced undergraduate students.
 
Genetic Theory and Analysis, 2nd edition readers will also find:
* Detailed treatment of subjects including mutagenesis, meiosis, complementation, suppression, and more
* Updated discussion of epistasis, mosaic analysis, RNAi, genome sequencing, and more
* Appendices discussing model organisms, genetic fine-structure analysis, and tetrad analysis
 
Genetic Theory and Analysis is ideal for both graduate students and advanced undergraduates undertaking courses in genetics, genetic engineering, and computational biology.

List of contents

Preface xi
 
Introduction xiii
 
1 Mutation 1
 
1.1 Types of Mutations 1
 
Muller's Classification of Mutants 2
 
Nullomorphs 2
 
Hypomorphs 4
 
Hypermorphs 5
 
Antimorphs 6
 
Neomorphs 8
 
Modern Mutant Terminology 10
 
Loss-of-Function Mutants 10
 
Dominant Mutants 10
 
Gain-of-Function Mutants 11
 
Separation-of-Function Mutants 11
 
DNA-Level Terminology 11
 
Base-Pair-Substitution Mutants 11
 
Base-Pair Insertions or Deletions 12
 
Chromosomal Aberrations 12
 
1.2 Dominance and Recessivity 13
 
The Cellular Meaning of Dominance 13
 
The Cellular Meaning of Recessivity 15
 
Difficulties in Applying the Terms Dominant and Recessive to Sex-Linked Mutants 16
 
The Genetic Utility of Dominant and Recessive Mutants 17
 
1.3 Summary 17
 
References 17
 
2 Mutant Hunts 20
 
2.1 Why Look for New Mutants? 20
 
Reason 1: To Identify Genes Required for a Specific Biological Process 21
 
Reason 2: To Isolate more Mutations in a Specific Gene of Interest 31
 
Reason 3: To Obtain Mutants for a Structure-Function Analysis 32
 
Reason 4: To Isolate Mutations in a Gene So Far Identified only by Computational Approaches 32
 
2.2 Mutagenesis and Mutational Mechanisms 32
 
Method 1: Ionizing Radiation 33
 
Method 2: Chemical Mutagens 33
 
Alkylating Agents 34
 
Crosslinking Agents 35
 
Method 3: Transposons 35
 
Identifying Where Your Transposon Landed 37
 
Why not Always Screen With TEs? 40
 
Method 4: Targeted Gene Disruption 40
 
RNA Interference 40
 
CRISPR/Cas9 41
 
TALENs 42
 
So Which Mutagen Should You Use? 43
 
2.3 What Phenotype Should You Screen (or Select) for? 44
 
2.4 Actually Getting Started 45
 
Your Starting Material 45
 
Pilot Screen 45
 
What to Keep? 45
 
How many Mutants is Enough? 46
 
Estimating the Number of Genes not Represented by Mutants in Your New Collection 46
 
2.5 Summary 48
 
References 48
 
3 Complementation 51
 
3.1 The Essence of the Complementation Test 51
 
3.2 Rules for Using the Complementation Test 55
 
The Complementation Test Can be Done Only When Both Mutants are Fully Recessive 55
 
The Complementation Test Does Not Require that the Two Mutants Have Exactly the Same Phenotype 56
 
The Phenotype of a Compound Heterozygote Can be More Extreme than that of Either Homozygote 56
 
3.3 How the Complementation Test Might Lie to You 57
 
Two Mutations in the Same Gene Complement Each Other 57
 
A Mutation in One Gene Silences Expression of a Nearby Gene 57
 
Mutations in Regulatory Elements 59
 
3.4 Second-Site Noncomplementation (Nonallelic Noncomplementation) 59
 
Type 1 SSNC (PoisonousInteractions): The Interaction is Allele Specific at Both Loci 60
 
An Example of Type 1 SSNC Involving the Alpha- and Beta-Tubulin Genes in Yeast 60
 
An Example of Type 1 SSNC Involving the Actin Genes in Yeast 62
 
Type 2 SSNC (Sequestration): The Interaction is Allele Specific at One Locus 66
 
An Example of Type 2 SSNC Involving the Tubulin Genes in Drosophila 66
 
An Example of Type 2 SSNC in Drosophila that Does Not Involve the Tubulin Genes 69
 
An Example of Type 2 SSNC in the Nematode Caenorhabditis elegans 71
 
Type 3 SSNC (Combined Haploinsufficiency): The Interaction is Allele-Independent at Both Loci 72
 
An Example of Ty

About the author

Danny E. Miller, MD, PhD is an Assistant Professor in the Department of Pediatrics, Division of Genetic Medicine and Laboratory Medicine & Pathology at the University of Washington in Seattle, WA, USA. He is the recipient of the 2017 Larry Sandler Memorial Award, the 2018 Lawrence E. Lamb Prize for Medical Research, and a 2022 National Institutes of Health Director's Early Independence Award. Dr Miller is a leader in the field of long-read sequencing technology and the use of new technology to evaluate individuals with unsolved genetic disorders. Angela L. Miller is a Research Coordinator at the University of Washington in Seattle, WA, USA, with a background in journalism, visual communications, and molecular biology. She has published several peer-reviewed papers and has won multiple national awards for her work as a journal art director. R. Scott Hawley, PhD is an Investigator at the Stowers Institute for Medical Research, Kansas City, MO, USA. He is a member of the National Academy of Sciences and former President of the Genetics Society of America, with faculty positions at the University of Kansas Medical Center and the University of Missouri-Kansas City. During his distinguished career, Dr. Hawley has mentored hundreds of trainees, received numerous genetics awards, written six textbooks, and published extensively on meiosis.

Product details

• Authors: R Scott Hawley, R. Scott Hawley, Hawley R. Scott, Angela L Miller, Angela L. Miller, Danny E Miller, Danny E. Miller, Danny E. (University of Washington Miller, Miller Angela L.
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Paperback / Softback
• Released: 02.11.2023
• EAN: 9781118086926
• ISBN: 978-1-118-08692-6
• No. of pages: 304
• Subjects: Natural sciences, medicine, IT, technology > Biology > Genetics, genetic engineering; Genetik, Medizin, Molekulargenetik, Life Sciences, genetics, Biowissenschaften, Medical Genetics, Medical Science, Medizinische Genetik, Molecular Genetics