Human Genetics, Concepts and Applications

475 Pages·2009·46.613 MB·English

by  R. Lewis

Cell and Molecular Biology
Human Genetics: Concepts and Applications
9th Edition
Lewis
(cid:2)(cid:3)(cid:4)
McGraw-Hill
McGraw−Hill Primis
ISBN−10: 0−39−023244−0
ISBN−13: 978−0−39−023244−1
Text:

Human Genetics: Concepts and
Applications, Ninth Edition
Lewis
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Cell and Molecular Biology
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111 0185GEN ISBN−10: 0−39−023244−0 ISBN−13: 978−0−39−023244−1
Cell and
Molecular
Biology
Contents
Lewis (cid:129) Human Genetics: Concepts and Applications, Ninth Edition
Front Matter 1
Preface 1
New to this Edition! 2
I. Introduction 3
1. Overview of Genetics 3
2. Cells 20
3. Meiosis and Development 46
II. Transmission Genetics 71
4. Single−Gene Inheritance 71
5. Beyond Mendel’s Laws 92
6. Matters of Sex 112
7. Multifactorial Traits 134
8. Genetics of Behavior 154
III. DNA and Chromosomes 170
9. DNA Structure and Replication 170
10. Gene Action: From DNA to Protein 184
11. Gene Expression and Epigenetics 204
12. Gene Mutation 216
13. Chromosomes 242
IV. Population Genetics 267
14. Constant Allele Frequencies 267
15. Changing Allele Frequencies 285
16. Human Ancestry 309
V. Immunity and Cancer 335
17. Genetics of Immunity 335
18. Genetics of Cancer 357
iii
VI. Genetic Technology 380
19. Genetic Technologies: Amplifying, Modifying, and Monitoring
DNA 380
20. Genetic Testing and Treatment 397
21. Reproductive Technologies 416
22. Genomics 432
Back Matter 449
Glossary 449
Credits 455
Index 457
iv
Lewis: Human Genetics: Front Matter Preface © The McGraw−Hill 1
Concepts and Applications, Companies, 2010
Ninth Edition
Preface
Human Genetics for Everyone T his new edition also reflects the shift in focus in the field
of human genetics from rare single-gene inheritance to more
common multifactorial traits and disorders.
Truth is indeed stranger than fiction. When I began writ-
ing this textbook 15 years ago with a glimpse of a fu-
The Human Touch
ture where two college roommates take tailored genetic
tests, I could never have imagined that today we would be H uman genetics is about people, and their voices echo through-
ordering such tests from websites. We send in our DNA out these pages. Most are real, some are composites, and many
on cheek swabs or in saliva samples to learn about our are based on the author’s experience as a science writer, genetic
genetic selves. We may receive risk estimates of future counselor, and hospice volunteer.
health concerns, or take ancestry tests that reveal our Compelling Stories and Case Studies Lewis enlivens her
pasts, noting which parts of the world our forebears like- clear presentation of genetic concepts with compelling stories
ly came from and maybe even who our distant cousins and cases like the following:
are. I’m amazed. ■ A young fashion magazine editor keeping her leukemia
Ricki Lewis at bay thanks to a drug developed through genetic
research (Ch. 18, p. 366)
■ A man freed from a 25-year prison term following
Today, human genetics is for everyone. It is about our varia-
reconsideration of DNA evidence (Ch. 14, p. 265)
tion more than about our illnesses, and increasingly about the
■ A father whose little girl has a condition so rare that it
common rather than the rare. Once an obscure science or an
doesn’t even have a name (Ch. 4, p. 69)
occasional explanation for an odd collection of symptoms, hu-
man genetics is now part of everyday conversation. At the same Practical Application of Human Genetics Recognizing that
time, it is finally being recognized as the basis of medical sci- the goal of most introductory science courses is to better inform
ence. Despite the popular tendency to talk of “a gene for” this future voters and consumers, the author provides practical ap-
or that, we now know that for most traits and illnesses, sev- plication of the content to students’ lives. Topics of particular
eral to many genes interact with each other and environmental interest to students include:
influences. By coming to know our genetic backgrounds, we
■ The role that genes play in disease susceptibility,
can control our environments in more healthful ways. G enetic
physical characteristics, body weight, and behaviors,
knowledge is, therefore, both informative and empowering.
with an eye toward the dangers of genetic determinism
This book shows you how and why this is true.
■ Biotechnologies, including genetic testing, gene therapy,
stem cell therapy, gene expression profiling, genome-
What Sets this Book Apart
wide association studies, and personalized medicine
■ Ethical concerns that arise from the interface of
Current Content
genetic information and privacy, such as infidelity
A s a member of the Information and Education Committee
testing, ancestry testing, and direct-to-consumer
of the American Society of Human Genetics, an instructor of
genetic testing
“Genethics,” genetic counselor, and long-time science writer,
Dr. Lewis is aware of research news and government policy The Lewis Guided Learning System
changes before they are published. The most exciting new de-
Each chapter is framed with a set of pedagogical features
velopments find their way into each edition of H uman Genet-
designed to reinforce the key ideas in the chapter and prompt
ics: Concepts and Applications, sometimes in the words of the
students to think more deeply about the application of the con-
people they directly affect. A few of the most compelling up-
tent they have just read.
dates to this edition include
Dynamic Art
■ Direct-to-consumer genetic testing
■ Genome-wide association (GWA) studies: promises and Outstanding photographs and dimensional illustrations, vibrant-
perils ly colored, are featured throughout H uman Genetics. Students
■ Gene expression profiling and personalized medicine will learn from a variety of figure types, including process fig-
■ Human microbiome project ures with numbered steps, micro to macro representations, and
■ Human variation and ancestry the combination of art and photos to relate stylized drawings to
■ GINA (Genetic Information Nondiscrimination Act) real-life structures.
■ Induced pluripotent stem cells (reprogramming)
xiii
2 Lewis: Human Genetics: Front Matter New to this Edition! © The McGraw−Hill
Concepts and Applications, Companies, 2010
Ninth Edition
New to this Edition!
N ew and updated information is integrated throughout the Chapter 11 Gene Expression and Epigenetics
chapters, and a few features from past editions have been ■ New Figure 11.7, Control of gene expression
moved. Highlights from the revision are included here. (transcription factors and microRNAs)
■ New text on the evolving definition of a gene
Chapter 1 Overview of Genetics
■ Updates on the Genetic Information Nondiscrimination Chapter 12 Gene Mutation
Act and the Human Microbiome Project ■ New chapter opening case study, “The Amerithrax Story”
■ New Figure 1.8 Diseasome—diseases are connected in ■ New Figure 12.1, Animal models of human diseases
unexpected ways ■ New Figure 12.11, Using copy number variants in
■ New Bioethics: Choices for the Future, “Genetic Testing healthcare
and Privacy”
Chapter 13 Chromosomes
Chapter 2 Cells ■ New Bioethics: Choices for the Future, “The Denmark
■ Stem cell coverage now stresses reprogrammed cells, Study: Screening for Down Syndrome”
with two new figures and a new Bioethics: Choices for
Chapter 16 Human Ancestry
the Future, “Should You Bank Your Stem Cells?”
■ New Bioethics: Choices for the Future, “Indigenous
■ New In Their Own Words, “A Little Girl with Giant
Peoples”
Axons”
■ Expanded coverage of markers, haplogroups, and
Chapter 4 Single-gene Inheritance migration
■ New chapter opener “His Daughter’s DNA,” about a ■ New Reading 16.2 “Should You Take a Genetic
father’s quest to solve a genetic mystery Ancestry Test?”
■ New section 4.1, A Tale of Two Families
Chapter 17 Genetics of Immunity
Chapter 5 Beyond Mendel’s Laws ■ Shortened and reorganized to stress genetics
■ New Reading 5.1, “The Genetic Roots of Alzheimer
Disease” Chapter 18 Genetics of Cancer
■ New Table 5.3, Types of Genetic Markers ■ New Table 18.2, Processes and Pathways Affected in
Cancer
Chapter 6 Matters of Sex ■ The cancer genome
■ New chapter opener, “A Controversial Hypothesis:
Mental Illness, Mom, and Dad” Chapter 19 Genetic Technologies: Amplifying, Modifying,
■ New Reading 6.2, “Rett Syndrome—A Curious and Monitoring DNA
Inheritance Pattern” ■ Expanded and updated information on DNA patents
■ New section 19.5, Silencing DNA (RNAi, antisense, and
Chapter 7 Multifactorial Traits
knockouts)
■ New Figure 7.1, Anatomy of a trait—rare single-gene
disorders versus common SNP patterns Chapter 20 Genetic Testing and Treatment
■ New section 7.4, Genome-wide association studies ■ New section 20.1, “Geneticists find zebras, and some
(including new figures 7.9 and 7.11) horses” (including new figure 20.1)
■ New information on direct-to-consumer tests and CLIA
Chapter 8 Genetics of Behavior
regulations
■ New section 8.5, How nicotine is addictive and raises
■ Gene therapy to treat hereditary blindness in an 8-year-
cancer risk
old
■ New section 8.8, Autism (includes new Figure 8.9,
Understanding autism) Chapter 22 Genomics
■ New chapter opener, “20,000 Genomes and Counting”
Chapter 9 DNA Structure and Replication
■ New Reading 22.1, “The First Three Humans to Have
■ New Bioethics: Choices for the Future, “Infidelity
Their Genomes Sequenced”
Testing”
xiv
Lewis: Human Genetics: I. Introduction 1. Overview of Genetics © The McGraw−Hill 3
Concepts and Applications, Companies, 2010
Ninth Edition
1
Introduction
P A R T
C H A P T E R
1
Personal genetic information is now readily
available. People use genetic information to
learn about their health risks and trace their
ancestry.
Overview of Genetics
Direct-to-Consumer Genetic Testing
Genetic tests were once used solely to diagnose conditions so rare that
doctors could not often match a patient’s symptoms to a recognized
illness. Today, taking a genetic test is as simple as ordering a kit on the
Internet, swishing a plastic swab inside the mouth, and mailing the
collected cell sample to a testing company or research project. The
Chapter Contents
returned information can reach back to the past to chart a person’s
1.1 Introducing Genes ancestry, or into the future to estimate disease risk.
1.2 Levels of Genetics
Some “direct-to-consumer” (dtc) genetic tests identify well-studied
The Instructions: DNA, Genes, Chromosomes,
mutations that cause certain diseases. Yet other tests are based on
and Genomes
“associations” of patterns of genetic variation that appear in people who
The Body: Cells, Tissues, and Organs
share certain traits or illnesses, but not nearly as often in others. Because
Relationships: From Individuals to Families
these new types of tests are drawn from population studies, they might
The Bigger Picture: From Populations to not apply to a particular person. Consumers who take Internet-offered
Evolution
tests can review results with a genetic counselor. If interpreted carefully,
1.3 Genes and Their Environment
information from genetic tests can be used to promote health or identify
1.4 Applications of Genetics relatives.
Establishing Identity
Eve is curious about her ancestry and future health, so she finds a
Health Care
company whose tests provide clues to both. Her DNA sample is scanned
Agriculture for variants inherited from her mother against a database of patterns
Ecology from 20 nations and 200 ethnic groups in and near Africa. Eve learns that
A Global Perspective her family on her mother’s side came from Gambia. She will be notified
of others who share this part of her deep ancestral roots.
1
4 Lewis: Human Genetics: I. Introduction 1. Overview of Genetics © The McGraw−Hill
Concepts and Applications, Companies, 2010
Ninth Edition
The health tests require more thought. Eve dismisses tests
for traits she considers frivolous—ear wax consistency and
ability to taste bitter foods—as well as for the obvious,
such as blue eyes, baldness, or obesity. She already knows
if she overeats and doesn’t exercise, she’ll gain weight.
Cancer and Alzheimer disease are too remote for a
20-year-old to think much about, so she foregoes those
tests too—for now.
Eve selects her health tests based on her family history—
she, a sister, and her father often have respiratory infections.
So she asks for her DNA to be tested for gene variants that
might affect breathing—cystic fibrosis, asthma,
emphysema, nicotine dependence, and lung cancer. Figure 1.1 Inherited traits. This young lady owes her red
hair, fair skin, and freckles to a variant of a gene that encodes a
Reluctantly she checks the boxes for heart and blood vessel
protein (the melanocortin 1 receptor) that controls the balance of
diseases, too. Her reasoning: She can do something pigments in the skin.
proactive to prevent or delay these conditions, such as
breathing clean air, exercising, not smoking, and following a
cells, the basic units of life, how to manufacture certain proteins.
healthy diet.
These proteins, in turn, impart or control the characteristics that
Is genetic testing something that you would do? create much of our individuality. A gene is the long molecule
deoxyribonucleic acid (DNA). It is the DNA that transmits
information, in its sequence of four types of building blocks.
1.1 Introducing Genes
T he complete set of genetic instructions characteristic of
an organism, including protein-encoding genes and other DNA
G enetics is the study of inherited traits and their variation. sequences, constitutes a g enome. Nearly all of our cells con-
Sometimes people confuse genetics with genealogy, which tain two copies of the genome. Researchers are still analyzing
considers relationships but not traits. With the advent of tests what all of our genes do, and how genes interact and respond
that can predict genetic illness, genetics has even been com- to environmental stimuli. Only a tiny fraction of the 3.2 billion
pared to fortunetelling! But genetics is neither genealogy nor building blocks of our genetic instructions determines the most
fortunetelling—it is a life science. interesting parts of ourselves—our differences. Comparing
Inherited traits range from obvious physical characteristics, and analyzing genomes, which constitute the field of genom-
such as the freckles and red hair of the girl in figure 1.1, to many ics, reveals how closely related we are to each other and to
aspects of health, including disease. Talents, quirks, behaviors, other species.
and other difficult-to-define characteristics might appear to be Genetics directly affects our lives, as well as those of our
inherited if they affect several family members, but may reflect relatives, including our descendants. Principles of genetics also
a combination of genetic and environmental influences. Some touch history, politics, economics, sociology, art, and psychol-
traits attributed to genetics border on the silly—such as sense of ogy. Genetic questions force us to wrestle with concepts of ben-
humor, fondness for sports, and whether or not one votes. efit and risk, even tapping our deepest feelings about right and
Until the 1990s, genetics was more an academic than a wrong. A field of study called bioethics was founded in the
clinical science, except for rare diseases inherited in clear pat- 1970s to address moral issues and controversies that arise in
terns in families. As the century drew to a close, researchers applying medical technology. Bioethicists today confront con-
completed the global Human Genome Project, which deciphered cerns that new genetic knowledge raises, such as privacy and
the complete set of our genetic instructions. The next step—sur- discrimination. Essays throughout this book address bioethical
veying our genetic variability—was already underway. Today, issues.
genetics has emerged as an informational as well as a life sci- M any of the basic principles of genetics were discov-
ence that is having a huge societal impact. Genetic information ered before DNA was recognized as the genetic material, from
is accessible to anyone, and the contribution of genes to the most experiments and observations on patterns of trait transmission
common traits and disorders is increasingly appreciated. in families. For many years, genetics textbooks (such as this
Like all sciences, genetics has its own vocabulary. Many one) presented concepts in the order that they were understood,
terms may be familiar, but actually have precise technical defini- discussing pea plant experiments before DNA structure. Now,
tions. All of the terms and concepts in this chapter are merely intro- since even gradeschoolers know what DNA is, a “sneak pre-
ductions that set the stage for the detail in subsequent chapters. view” of DNA structure and function is appropriate ( Reading
Genes are the units of heredity, which is the transmission 1.1 ) to consider the early discoveries in genetics (chapter 4)
of inherited traits. Genes are biochemical instructions that tell from a modern perspective.
2 Part 1 Introduction
Lewis: Human Genetics: I. Introduction 1. Overview of Genetics © The McGraw−Hill 5
Concepts and Applications, Companies, 2010
Ninth Edition
Reading 1.1
Introducing DNA
We have probably wondered about heredity since our beginnings, In the late nineteenth century, when Gregor Mendel bred
when our distant ancestors noticed family traits such as a beaked pea plants to follow trait transmission, establishing the basic laws
nose or an unusual skill, such as running fast or manual dexterity. of inheritance, he inferred that units of inheritance were at play. He
Awareness of heredity appears in ancient Jewish law that excuses a had no knowledge of cells, chromosomes, or DNA. This short reading
boy from circumcision if his brothers or cousins bled to death following explains, very briefly, what Mendel did not know—how DNA confers
the ritual. Nineteenth-century biologists thought that body parts inherited traits. Chapter 9 examines DNA in detail.
controlled traits, and they gave the hypothetical units of inheritance DNA resembles a spiral staircase or double helix in which the
such colorful names as “pangens,” “ideoblasts,” “gemules,” and simply “rails” or backbone of alternating sugars and phosphates is the same
“characters.” from molecule to molecule, but the “steps” are pairs of four types of
building blocks, or DNA bases, whose sequence varies (figure 1). The
5′ 5′ 3′ 3′ chemical groups that form the steps are adenine (A) and thymine (T),
P which attract, and cytosine (C) and guanine (G), which attract. DNA
A T P holds information in the sequences of A, T, C, and G. The two strands
are oriented in opposite directions.
P C G DNA uses its information in two ways. If the sides of the
P
helix part, each half can reassemble its other side by pulling in free
P building blocks—A and T attracting and G and C attracting. This
G C P process, called DNA replication, maintains the information when the
cell divides. DNA also directs the production of specific proteins. In
P T A
a process called transcription, the sequence of part of one strand of
P
a DNA molecule is copied into a related molecule, messenger RNA.
P C G Each three such RNA bases in a row attract another type of RNA that
P
functions as a connector, bringing with it a particular amino acid,
3′ P G C P 5′ which is a building block of protein. The synthesis of a protein is
called translation. As the two types of RNA temporarily bond, the
P
A T P amino acids align and join, forming a protein that is then released.
G C DNA, RNA, and proteins can be thought of as three related languages
A of life (figure 2).
G C
A T
C G
T A Replication
DNA
C G
T A Transcription
G C
A T RNA
G C Nucleus
Translation
A T
C G
5′ 3′ Protein
Cytoplasm
Figure 1 The DNA double helix. The 5′ and 3′ labels indicate the
head-to-tail organization of the DNA double helix. A, C, T, and G are bases.
S stands for sugar and P for phosphate. Figure 2 The language of life: DNA to RNA to protein.
Chapter 1 Overview of Genetics 3