Human Genetics: Concepts and Applications

482 Pages·2014·39.361 MB·English

by  Ricki Lewis

Final PDF to printer
eleventh edition
Human Genetics
Concepts and Applications
Ricki Lewis
Genetic Counselor
CareNet Medical Group
Schenectady, New York
Adjunct Assistant Professor of
Medical Education
Alden March Bioethics Institute
Albany Medical College
Writer, Medscape Medical News
Blogger, Public Library of Science
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HUMAN GENETICS: CONCEPTS AND APPLICATIONS, ELEVENTH EDITION
Published by McGraw-Hill Education, 2 Penn Plaza, New York, NY 10121. Copyright © 2015 by McGraw-Hill
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All credits appearing on page or at the end of the book are considered to be an extension of the copyright page.
Library of Congress Cataloging-in-Publication Data
Lewis, Ricki.
Human genetics : concepts and applications/Ricki Lewis, Genetic Counselor, CareNet Medical Group, Sche-
nectady, New York, Adjunct Assistant Professor of medical education, Alden March Bioethics Institute, Albany
Medical College, writer, Medscape Medical News, blogger, Public Library of Science.—Eleventh edition.
pages cm
ISBN 978-0-07-352536-5 (alk. paper)
1. Human genetics—Textbooks. I. Title.
QH431.L41855 2015
599.93’5—dc23
2014020906
The Internet addresses listed in the text were accurate at the time of publication. The inclusion of a website does
not indicate an endorsement by the authors or McGraw-Hill Education, and McGraw-Hill Education does not
guarantee the accuracy of the information presented at these sites.
www.mhhe.com
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About the Author
Ricki Lewis has built an eclectic career in communicating the excitement of genetics
and genomics. She earned her Ph.D. in genetics in 1980 from Indiana University.
It was the dawn of the modern biotechnology era, which Ricki chronicled in many
magazines and journals. She published one of the first articles on DNA fingerprinting
in Discover magazine in 1988, and a decade later one of the first articles on human
stem cells in The Scientist.
Ricki has taught a variety of life science courses at Miami University, the University
at Albany, Empire State College, and community colleges. She has authored or
co-authored several university-level textbooks and is the author of The Forever Fix:
Gene Therapy and the Boy Who Saved It, as well as an essay collection and a novel .
Ricki has been a genetic counselor for a private medical practice since 1984 and is
a frequent public speaker. Since 2012, Ricki has written hundreds of news stories
for Medscape Medical News, articles for Scientific American and for several genetic
disease organizations, and originated and writes the popular weekly DNA Science
blog at Public Library of Science.
Ricki teaches an online course on “Genethics” for the Alden March Bioethics Institute
of Albany Medical College. She lives in upstate New York and sometimes Martha’s
Vineyard, with husband Larry and several felines. Contact Ricki at rickilewis54@gmail.
com , or join the discussion on DNA Science at h ttp://blogs.plos.org/dnascience/.
DDeeddiiccaatteedd ttoo tthhee
families who live with genetic diseases, the
health care providers who help them, and
the researchers who develop new tests
and treatments.
iii
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Brief Contents
1 12
C H A P T E R
Gene Mutation 212
PPP AA R T
13
Introduction 1 C H A P T E R
Chromosomes 237
1
C H A P T E R 4
What Is in a Human Genome? 1

2 PPP AA R T
C H A P T E R
Cells 15 Population Genetics 263
3
C H A P T E R 14
Meiosis, Development, and Aging 42 C H A P T E R
Constant Allele Frequencies 263
2 15
C H A P T E R
Changing Allele Frequencies 279
PPP AA R T
16
T ransmission C H A P T E R
Human Ancestry and Evolution 302
Genetics 68
5
4
C H A P T E R PPP AA R T
Single-Gene Inheritance 68
Immunity and
5
C H A P T E R
Beyond Mendel’s Laws 89 Cancer 326
6
C H A P T E R 17
Matters of Sex 110 C H A P T E R
Genetics of Immunity 326
7
C H A P T E R 18
Multifactorial Traits 130 C H A P T E R
Cancer Genetics and Genomics 351
8
C H A P T E R
Genetics of Behavior 148 6

3 PPP AAA R T

Genetic Technology 374
P PP AA R T
D NA and 19
C H A P T E R
Genetic Technologies: Patenting, Modifying, and
Chromosomes 163
Monitoring DNA 374
9 20
C H A P T E R C H A P T E R
DNA Structure and Replication 163 Genetic Testing and Treatment 389
10 21
C H A P T E R C H A P T E R
Gene Action: From DNA to Protein 180 Reproductive Technologies 407
11 22
C H A P T E R C H A P T E R
Gene Expression and Epigenetics 199 Genomics 425
iv
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Contents
About the Author i ii
Preface i x
Applying Human Genetics x iii
The Human Touch xiv
The Lewis Guided Learning System x v
1
Introduction 1
P A R T
1 3
CCC HHH A P T E R CCC HHH A P T E R
What Is in a Human Meiosis, Development,
Genome? 1 and Aging 42
1.1 Introducing Genes and Genomes 2 3.1 The Reproductive System 43
1.2 Levels of Genetics and Genomics 3 3.2 Meiosis 44
1.3 Applications of Genetics and Genomics 7 3.3 Gametes Mature 47
1.4 A Global Perspective on Genomes 9 3.4 Prenatal Development 51
3.5 Birth Defects 59
2
3.6 Maturation and Aging 62
C CCC HHH A P T E R
Cells 15
2.1 Introducing Cells 16
2.2 Cell Components 16
2.3 Cell Division and Death 28
2.4 Stem Cells 33
2.5 The Human Microbiome 37
2
Transmission Genetics 6 8
P A R T
4
C CC HHH A P T E R 4.3 Following the Inheritance of More Than
One Gene 77
Single-Gene
4.4 Pedigree Analysis 79
Inheritance 68
4.5 Family Exome Analysis 83
4.1 Following the Inheritance of One Gene 69
4.2 Single-Gene Inheritance
Is Rare 72
v
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5 7
CCC HHH A P T E R CCC HHH A P T E R
Beyond Mendel’s Multifactorial Traits 130
Laws 89
7.1 Genes and the Environment Mold Traits 131
7.2 Polygenic Traits Are Continuously Varying 133
5.1 When Gene Expression Appears to Alter
Mendelian Ratios 90 7.3 Methods to Investigate Multifactorial
Traits 135
5.2 Mitochondrial Genes 98
7.4 A Closer Look: Body Weight 142
5.3 Linkage 100
8
6
CCC HHH A P T E R
I 1 2
II 1 2 3 4 CCC HHH A P T E R
III 1 2 34567891011 Genetics of Behavior 148
IVV11 22345 Matters of Sex 110
8.1 Genes and Behavior 149
6.1 Our Sexual Selves 111
8.2 Sleep 150
6.2 Traits Inherited on Sex Chromosomes 117 8.3 Intelligence and Intellectual Disability 151
6.3 Sex-Limited and 8.4 Drug Addiction 152
Sex-Influenced Traits 122
8.5 Mood Disorders 154
6.4 X Inactivation 122 8.6 Schizophrenia 155
6.5 Parent-of-Origin Effects 124 8.7 Autism 157
3
DNA and Chromosomes 1 63
P A R T
9 10
CCC HHH A P T E R moiunpo gHHroRupN HCCCCHHH222 C OOAHrgininegAroc CCC HHH A P T E R
NH
DNA Structure C Gene Action: From DNA
H2N NH
and Replication 163 to Protein 180
9.1 Experiments Identify and Describe the 10.1 Transcription Copies the Information in
Genetic Material 164 DNA 181
9.2 DNA Structure 168 10.2 Translation of a Protein 186
9.3 DNA Replication—Maintaining Genetic 10.3 Processing a Protein 192
Information 170
9.4 Sequencing DNA 176
vi Contents
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11 12.4 Causes of Mutation 218
CCC HHH A P T E R 12.5 Types of Mutations 221
Gene Expression 12.6 The Importance of Position 227
12.7 DNA Repair 229
and Epigenetics 199
13
11.1 Gene Expression Through Time
and Tissue 200 CCC HHH A P T E R
11.2 Control of Gene Expression 203 Chromosomes 237
11.3 Maximizing Genetic Information 205
13.1 Portrait of a Chromosome 238
11.4 Most of the Human Genome Does Not
Encode Protein 206 13.2 Detecting Chromosomes 240
13.3 Atypical Chromosome Number 244
12
13.4 Atypical Chromosome Structure 253
CCC HHH A P T E R
13.5 Uniparental Disomy—A Double Dose from
Gene Mutation 212 One Parent 258
12.1 The Nature of Mutations 213
12.2 A Closer Look at Two Mutations 214
12.3 Allelic Disorders 217
4
Population Genetics 263
P A R T
14
CCC HHH A P T E R 15.3 Genetic Drift 282
Constant Allele 15.4 Mutation 286
15.5 Natural Selection 287
Frequencies 263
15.6 Eugenics 295
14.1 Population Genetics Underlies
16
Evolution 264
CCC HHH A P T E R
14.2 Constant Allele Frequencies 265
Human Ancestry
14.3 Applying Hardy-Weinberg Equilibrium 267
14.4 DNA Profiling Uses Hardy-Weinberg and Evolution 302
Assumptions 268
16.1 Human Origins 303
15
16.2 Methods to Study Molecular Evolution 311
CCC HHH A P T E R
16.3 The Peopling of the Planet 314
Changing Allele
16.4 What Makes Us Human? 318
Frequencies 279
15.1 Nonrandom Mating 280
15.2 Migration 281
Contents vii
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5
Immunity and Cancer 3 26
P A R T
17 18
CCC HHH A P T E R CCC HHH A P T E R
Genetics of C ancer Genetics
Immunity 326 and Genomics 351
17.1 The Importance of Cell Surfaces 327 18.1 Cancer Is an Abnormal Growth That Invades
and Spreads 352
17.2 The Human Immune System 330
18.2 Cancer at the Cellular Level 356
17.3 Abnormal Immunity 335
18.3 Cancer Genes and Genomes 360
17.4 Altering Immunity 341
18.4 The Challenges of Diagnosing and Treating
17.5 Using Genomics to Fight Infection 345 Cancer 369
6
Genetic Technology 3 74
P A R T
19 21
Cell
Mitochondria
CCC HHH A P T E R CCC HHH A P T E R
MDMNiittooAcchhoonnddrriiaoln
Genetic Technologies: MDNitoAc =ho 3n7d rgiaelnes Reproductive
Patenting, Modifying, Technologies 407
and Monitoring DNA 374
21.1 Savior Siblings and More 408
21.2 Infertility and Subfertility 409
19.1 Patenting DNA 375
21.3 Assisted Reproductive Technologies 411
19.2 Modifying DNA 376
21.4 Extra Embryos 419
19.3 Monitoring Gene Function 382
19.4 Gene Silencing and Genome 22
Editing 384
CCC HHH A P T E R
20 Genomics 425
CCC HHH A P T E R
22.1 From Genetics to Genomics 426
Genetic Testing and
22.2 Analysis of the Human Genome 430
Treatment 389
22.3 Personal Genome Sequencing 435
20.1 Genetic Counseling 390
Glossary G-1
20.2 Genetic Testing 392
20.3 Treating Genetic Disease 397 Credits C-1
Index I-1
viii Contents
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Preface
Human Genetics Touches Us All What Sets This Book Apart
Current Content
W hen I wrote the first edition of this book, in 1992,
I could never have imagined that today, thousands of T he exciting narrative writing style, with clear explanations
people would have had their genomes sequenced. Nor of concepts and mechanisms propelled by stories, reflects
could I have imagined, when the first genomes were Dr. Lewis’s eclectic experience as a medical news writer, blog-
sequenced a decade later, that the process could take ger, professor, and genetic counselor, along with her expertise
under a day, for less than $1,000. Of course, under- in genetics. Updates to this edition include
standing all the information in a human genome will
■ Genetic tests, from preconception to old age
take much longer.
■ Disease-in-a-dish stem cell technology
E ach subsequent edition opened with a scenario
■ From Mendel to molecules: family exome analysis
of two students taking genetic tests, which grew less
■ Allelic diseases: one gene, more than one disease
hypothetical and more real over time, even reaching the
■ Admixture of archaic and modern humans
direct-to-consumer level. This new edition reflects the
■ Gene silencing and genome editing
translation of gene and genome testing and manipulation
■ Cancer genomes guide treatment
from the research lab to the clinic.
■ The reemergence of gene therapy
The eleventh edition opens with “E ve’s
■ Personal genome sequencing: promises and limitations
Genome” and ends with “ Do You Want Your Genome
Sequenced?” In between, the text touches on what T he transition of genetics to genomics catalyzed slight reorga-
exome and genome sequencing have revealed about nization of the book. The order of topics remains, but material
single-gene diseases so rare that they affect only a sin- that had been boxed or discussed in later chapters because it
gle family, to clues to such common and complex condi- was once new technology has been moved up as the “applica-
tions as intellectual disability and autism. Exome and tions” become more integrated with the “concepts.” The book
genome sequencing are also important in such varied has evolved with the science.
areas as understanding our origins, solving crimes,
The Human Touch
and tracking epidemics. I n short, DNA sequencing will
affect most of us. H uman genetics is about people, and their voices echo through-
As the cost of genome sequencing plummets, we out these pages. They speak in the narrative as well as in many
all may be able to look to our genomes for echoes of new chapter introductions, boxes, stories, and end-of-chapter
our pasts and hints of our futures—if we so choose. We questions and cases.
may also learn what we can do to counter our inherited Compelling Stories and Cases When the parents of children
tendencies and susceptibilities. Genetic knowledge is
with visual loss stood up at a conference to meet other families
informative and empowering. This book shows you how
with the same very rare inherited disease, Dr. Lewis was there,
and why this is true.
already composing the opening essay to chapter 5. She knows
Ricki Lewis the little girl in the “ In Their Own Words ” essay in chapter 2
and on the cover with her dog, who is 1 of about 70 people
in the world with giant axonal neuropathy. Perhaps there is no
more heart-wrenching image of Mendelian inheritance than
T oday, human genetics is for everyone. It is about our variation the chapter 4 opening photo of a daughter and father, who died
more than about our illnesses, and about the common as well as from Huntington disease within weeks of each other.
the rare. Once an obscure science or an explanation for an odd
C linical Application of Human Genetics A working knowl-
collection of symptoms, human genetics is now part of everyday
edge of the principles and applications of human genetics is
conversation. At the same time, it is finally being recognized as
critical to being an informed citizen and health care consumer.
the basis of medical science, and health care professionals must
Broad topics of particular interest include
be fluent in the field’s language and concepts. Despite the popu-
lar tendency to talk of “a gene for” this or that, we now know ■ The roles that genes play in disease risk, physical
that for most traits and illnesses, several genes interact with each characteristics, and behavior, with an eye toward the
other and environmental influences to mold who we are. dangers of genetic determinism
ix
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