Danny E. Miller (University of Washington, Seattle, WA), Angela L. Miller (University of Washington, Seattle, WA), R. Scott Hawley (Kansas Cit Stowers Institute for Medical Research

Genetic Theory and Analysis

Finding Meaning in a Genome

• Broschiertes Buch

Produktbeschreibung

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.

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Produktdetails

• Verlag: Wiley & Sons / Wiley-Blackwell
• Artikelnr. des Verlages: 1W118086920
• 2. Aufl.
• Seitenzahl: 304
• Erscheinungstermin: 29. August 2023
• Englisch
• Abmessung: 253mm x 176mm x 17mm
• Gewicht: 673g
• ISBN-13: 9781118086926
• ISBN-10: 1118086929
• Artikelnr.: 63589424

Autorenporträt

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.

Inhaltsangabe

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