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Genetics and
Genomics
in Nursing and Health Care
viii Preface

5. Genomics and diseasemanagement

The three chapters in this focus area include thought-provoking issues regarding the benefits and risks of genetic
testing and the roles of various professionals in the genetic counseling process. Additionally, personalized health
care and "precision medicine," especially the variation in responses to drug therapy, are explored and explained.
6. Global genomic issues
The two chapters in this focus area concern the questions "How did we get here?" and "Where are we going?"
They explain the reasons why the predisposition and expression of some genetic disorders are greater for some
ethnic groups than for others. They also present issues and potential problems people are likely to face as they
rush into the genomic era of health care.
The style of presentation for the content of this textbook is direct, active, and clear. Health-care terms and
related physiological mechanisms are explained in common, everyday language to promote better student
understanding and continuous application of the content. Illustrations and tables were selected and devel-
oped to enhance student understanding of cellular activities, inheritance patterns, and genetic risks. The use
of color and new illustrations is expected to help achieve the goal of student understanding.
We have included key features in each chapter. Each chapter opens with a list of learning outcomes fol-
lowed by a list of key terms. Each key term is also presented in the chapter text and highlighted in boldface
when first used. A full alphabetical listing of key terms with definitions can be found in the glossary at the
end of the text. At the end of each chapter, there is a list of Gene Gems highlighting essential key points
for the student co take away from the reading. Students will also find self-assessment questions keyed to
the learning outcomes of the chapter. The answers for these can be found at the end of each chapter. Finally,
critical thinking case studies are located at the end of every clinical chapter. These realistic cases present issues
and problems that require clinical decision making about individual patients and families that are at increased
genetic risk for health problems.
Additional materials and study cools can be found on DavisPlus, including activities for critical thinking
and learning key terms, links to online genetics resources, and extensive teaching resources for instructors.
Janet Adams, MSN, RT (ARRT), RN Elizabeth Louise Pestka, MS, RN,
Instructor PMHCNS-BC, APNG
Southeast Missouri State University Assistant Professor of Nursing & Clinical Nurse
Cape Girardeau, Missouri Specialist
Mayo Clinic
Julie Baldwin, RN, MSN Rochester, Minnesota
Assistant Professor of Nursing
Missouri Western State University Michael A. Rackover, PA-C, MS
St. Joseph, Missouri PA Program Director & Associate Professor
Philadelphia University
Laurie Brooks, MSN, MBA, RN Philadelphia, Pennsylvania
Assistant Professor
Saint Luke's College of Health Sciences Catherine Read, PhD, RN
Kansas City, Missouri Associate Dean/Associate Professor
Connell School of Nursing, Boston College
Deborah Ellis, RN, MSN, NP-C Chestnut Hill, Massachusetts
Assistant Professor
Missouri Western State University Jackie Shrock, RN, BSN, MEd
St. Joseph, Missouri Nursing Program Coordinator/Teacher
Wayne County Schools Career Center
Kathleen T. Hickey, EdD, FNP-BC, ANP-BC Orrville, Ohio
Assistant Professor of Nursing
Columbia University Yona D. Victor, MD
New York, New York Full-Time Faculty
The School of Nursing at Platt College
Anita H. King, DNp, MA, FNP-BC, CDE, FAADE Aurora, Colorado
Clinical Associate Professor, College of Nursing
University of South Alabama Lottchen Wider, RN, PhD
Fairhope, Alabama Associate Professor
Maryville University
Judith A. Lewis, PhD, RN, WNP-BC, FAAN S(. Louis, Missouri
Professor Emerita
Virginia Commonwealth University
Richmond, Virginia

Carrie J. Merkle, PhD, RN, FAAN

Associate Professor
University of Arizona College of Nursing
Tucson, Arizona

ix
Many talented people are needed to make any textbook a success. The authors wish to acknowledge the fol-
lowing individuals for their guidance, dedication, hard work, constructive criticism, and creative input that
were so important to this project: Kelly Horvath, Amy Romano, and Susan Rhymer.

x
 abla.ot.C
UNIT I Basic Concepts From Chapter 5 Epigenetic Influences
Molecular Genetics 1 on Gene Expression 96
Introduction 96
Chapter 1 DNA Structure and Function 2
Microbiome 100
Introduction 3
Epigenetics and Cancer 101
Genetic Biology 3
Nature and Nurture Working
DNA 5
Together 103
Chapter 2 Protein Synthesis 23 The Future of Epigenetics:
Introduction 24 Are There Clinical
Transcription 26 Applications? 105
Translation 30 Chapter 6 Autosomal Inheritance
Mutations 35 and Disorders 109
Summary 40 Introduction 109
Chromosomal Inheritance 110
Chapter 3 Genetic Influences on Cell
Division, Cell Differentiation, Common Chromosomal
and Gametogenesis 43 Disorders 115
Introduction 44
Summary 127
Normal Cell Biology 44 Chapter 7 Sex Chromosome
Early Embryonic Cell Biology 52 and Mitochondrial
Commitment and Inheritance
Differentiation 54 and Disorders 130
Gametogenesis 56 Introduction 131
Summary 65 Extra X Chromosomes 131
Extra Y Chromosomes 132
UNIT II Gene Expression 69 Monosomy 133
Chapter 4 Patterns of Inheritance 70 Genotype-Phenotype Gender
Introduction 70 Mismatch 135
Mendelian Inheritance 71 Fragile X Syndrome 138
Punnett Square Analysis Mitochondrial Gene
and Probability 84 Inheritance 140
Chromosomal Inheritance 85 Summary 147
Complex (Multifactorial) Chapter 8 Family History and Pedigree
Disease 85 Construction 152
Genomic Variation Influencing Introduction 152
Susceptibilityand Resistance
to Health Problems 89 Family History 153
Summary 92 Pedigree Construction 155

xi
xii Table of Contents

Punnett Squares 158 UNIT IV Genomic Influences

Pedigree Analysis 159 on Selected Complex
Summary 161 Health Problems 263
Chapter 9 Congenital Anomalies, Chapter 13 Cardiovascular Disorders 264
Basic Dysmorphology, Introduction 265
and Genetic Assessment 167 Atherosclerosis and Coronary
Introduction 168 Artery Disease 265
Major and Minor Anomalies 169 Stroke 268
Classification of Congenital Hypertension 271
Anomalies 170 Arrhythmias 272
Syndrome or Sequence 172 Cardiomyopathy 274
Dysmorphology Assessment 173 Summary 278
Assessment Through
Chapter 14 The Genetics of Cancer 283
a Genetic Lens 175
Summary 185 Introduction 283
Benign Tumor Cells 284
UNIT III Genomic Health Problems Cancer Cells 286
Across the Life Span 189
Cancer Development 287
Chapter 10 Enzyme and Collagen Summary 299
Disorders 190
Chapter 15 Genetic Contributions
Introduction 191
to Psychiatric
Enzyme Disorders 191 and Behavioral
Collagen Disorders 200 Disorders 303
Summary 207 Introduction 303
Chapter 11 Common Childhood-Onset Genetics Applications
Genetic Disorders 211 for the Psychiatric
Patient 304
Introduction 212
Autism 306
Monogenic Disorders 212
Attention-Deficit
Complex Disorders 226
Hyperactivity Disorder 308
Summary 234
Schizophrenia 309
Chapter 12 Common Adult-Onset AffectiveDisorders 311
Genetic Disorders 239 Substance Use Disorders 312
Introduction 239 Personality Disorders 314
Monogenic Disorders 240 Sununary 316
Complex Disorders 245
Diseases Affecting Older
Adults 253
Summary 257
 Table of Contents xiii

UNITV Genomics and Disease UNITVI Global Genomic

Management 321 Issues 373
Chapter 16 Genetic and Genomic Chapter 19 Financial, Ethical, Legal,
Testing 322 and Social Considerations 374
Introduction 322 Introduction 374
Genetic Testing Samples 323 Ethical Goals of Clinical
Types of Genetic Tests 326 Genetics 375
Oversight of Genetic Testing 331 Genetic Discrimination 375
Laboratory Methods Used Duty to Warn Versus
for Genetic Testing 332 the Right to Privacy 378
Direct-to-Consumer Genetic Intellectual Property Rights
Testing 334 and Gene Patents 381
Risks and Benefits of Genetic Gene Therapy 381
Testing 334 Summary 383
Summary 337 Chapter 20 Genetic and Genomic
Chapter 17 Assessing Genomic Variation 387
Variation in Drug Response 341 Introduction 387
Introduction 341 Population Genetics 388
Pharmacodynamics 344 Race,Ethnicity, and Human
Pharmacokinetics 346 Genetic Variation 394
Genetic/Genomic Variations 350 Summary 395
Clinical Applications Appendices
of Pharmacogenomics 354
Appendix A Genetics Organizations
Genetic Testing for Drug
Response 356 and Support Groups 399
Summary 357 Appendix B Selected Educational
Websites 400
Chapter 18 Health Professionals
and Genomic Care 360 Glossary 402
Introduction 360 Index 423
Genetics Professionals 361
Role of General Nurses
in Genomic Care 364
Interdisciplinary Health -Care
Professionals 366
Summary 370
Basic Concepts From
Molecular Genetics
 DNA Structure and Function

Learning Outcomes
1. Compare the components, structures, and forms of DNA.
2. Describe the events and processes involved in DNA replication.
3. Explain the formation and purpose of chromosomes.
4. Assess a karyotype for gender and ploidy.
5. Distinguish genotype from phenotype.
6. Explain how dominant gene alleles and recessive gene alleles determine expression of single-gene traits.

Key Terms
Allele Dominant trait Nucleoside
Aneuploid Euploid Nucleotide
Autosomes Gene p arm
Base pairs Gene locus Phenotype
Bases Genetics Ploidy
Centromere Genome Polyploidy
Chromatid Genomics Proteome
Chromosome Genotype Proteomics
Codominant trait Haploid chromosome number Recessive trait
Complementary pairs Heterozygous q arm
Deoxyribonucleic acid (DNA) Histones Sex chromosomes
Diploid chromosome number Homozygous Single-gene trait
DNA replication Karyotype
DNA synthesis Mitosis

2
 Chapter 1 DNA Structure and Function 3

INTRODUCTION
Genetics and genomics are common issues that have an impact on the health and well-being of everyone.
All health-care professionals are expected to be familiar with basic terminology and patterns of inheritance to
recognize when a patient or family has a possible genecic risk for a health problem. The use of genetics and
genomics can assist in developing health-problem prevention strategies and precision therapies that take into
account each person's genetic differences. This chapter presents informacion about basic genetics to help your
understanding of how this information can have an impact on caring for patients and families.
The terms genetics and genomics are often used interchangeably, although there are some differences.
Genetics is the study of the general mechanisms of heredity and the variation of inherited traits. Genomics
is the study of the function of all the nucleotide sequences present within the entire genome of a species,
including genes in deoxyribonucleic acid (DNA) coding regions and in the DNA noncoding regions. (Coding
regions and noncoding regions are discussed in Chapter 2.) These definitions indicate that genomics includes
genetics but has a broader scope.

GENETIC BIOLOGY
All living cells, even bacteria and other lower organisms, have genes. A gene is a specific set of instructions cells
use to produce a specific protein. Consider all the hormones, enzymes, and other proteins your body makes,
both those that exist as individual, identifiable substances and those that are parts of larger components. Some
genes tell each ceU what protein to make and how to make it, whereas other genes control a cell's protein-
making activity by determining when to make a specific protein and how much to make. Thus, a gene acts
as a specific "recipe" for making a protein.
Most genes are part of the DNA in the nucleus of body cells. Figure I-I shows a cell nucleus with DNA
in the form of chromosomes. Figure 1-2 depicts an enlarged chromosome to show that a chromosome is
composed of DNA and contains segments that are genes.

Figure 1-1 Human cell and its nucleus with

metaphase chromosomes.

Metaphasechromosomes
withinthe nucleus

• Maternal-originchromosome
• Paternal-originchromosome
4 Unit I Basic Concepts From Molecular Genetics

All human cells with a nucleus contain rwo sets of every gene that humans possess. This complete set of
genes for our species is called the human genome and contains between 20,000 and 25,000 individual genes.
(Mature germ cells-sperm and ova-contain only one set of every human gene.) The fact that all nucleated
cells contain all the human genes can be a confusing concept because no single cell type produces all the
proteins coded for by these genes. For example, only the thyroid gland normally produces thyroid hormones,
even though all cells have the genes for thyroid hormones. Although genes for thyroid hormones are present
in all cells, they are selectively activated and expressed exclusively in the thyroid gland, resulting in the pro-
duction of thyroid hormones. The activation of a gene allowing its product to be made by the cell is called
gene expression. In all other cell types, regulator genes prevent the structural genes for thyroid hormones from
being expressed.
The complete set of all proteins that a person makes at a given time under certain conditions is called the
proteome. This term combines the word protein and suffix -ome to indicate the totality of all proteins found
in a person, organ, tissue, or cell. The study of how proteins found in the proteome interact with each other
is known as proteomics. Proreornes can be examined for one cell type or for an entire organism. The protein
estrogen is part of the proteome for ovarian cells but is not part of the cardiac muscle cell (myocardial cell)
proteome. When considering the entire human proteome, we are looking at the proteins produced by all the
individual cellular proteomes. Proreornes are discussed in more detail in Chapter 2.
Although DNA appears different from a gene and from a chromosome, they are all the same substance.
DNA is the basic genetic chemical structure, containing gene-coding regions and noncoding regions, which
can be compressed into a chromosome form (see Fig. 1-2). A chromosome is a temporary but consistent
state of condensed DNA structure formed for the purpose of cell division. Chromosomes are discussed later
in this chapter. Just remember that genes and chromosomes are both composed of DNA. Consider a sweater
as a chromosome and each separate part of the sweater (right sleeve, left sleeve, pocket, collar, front, and back)
as a gene. Now consider that the entire sweater (chromosome) and its parts (genes) are composed of yarn

-- One small segment

01 DNA containing
Nucleated cell a single gene

~e_.A
Nucleus containing
Gene 2-

the entire genome

C-G
Centromere -A
C-G
One chromatid,-- A-
the longitudinal -A
half of a chromosome G-C

Chromosome composed of a large I Six base pairs

segment of DNA containing as many Double helix composed 01 12
as 1,000 individual genes 01 DNA individual nucleotides

Figure 1-2 Different forms of cellular (nuclear) DNA.

 Chapter 1 DNA Structure and Function 5

_Telomere
(telomericDNA)

parm

Insulin gene region (11q13){ h:~- ....

13.4
....,j

13.5
14.1
14.2
14.3
21
21.1 qarm
22.2
22.3
23.1
23.2
23.3
24- __ Figure 1-3 Banded chromosome 11 showing
25 -,---, locus of insulin gene (11q13) and the telomeres
Telomere (telomericDNA)____..
that "cap" the ends of the chromosome.

(DNA). A sweater is not a person's entire wardrobe, however, just like one chromosome and all the genes it
contains are not the entire genome. Think of the genome as being the entire wardrobe (all the person's shoes,
socks, underpants, undershirrs, pants, shirts, sweaters, coats, hats, gloves, and scarves). Each chromosome has
many genes within it. Larger chromosomes contain thousands of genes, and smaller chromosomes may have
fewer than 100 genes.
Another analogy for understanding how DNA, chromosomes, and genes are connected is to consider the
DNA of the genome to be a large recipe book with all the instructions (recipes) needed to make every protein
your body can produce. Each chromosome is a separate chapter, and the genes are the individual recipes. Each
gene has a specific chromosome location, called a gene locus; think of this as the "page" of the chapter where
the recipe is located. For example, the insulin gene's locus is llq 13, which means that the gene is located on
the long arm of chromosome 11 in region 13 (Fig. 1-3). When it is time to make more insulin, this is the
"page" where the recipe can be found, Although all ceLIshave the "recipe" for insulin on chromosome 11, it is
only opened and read by the beta cells of the pancreas. Other cells normally cannot "read" the insulin recipe
and do not make insulin. Protein synthesis, which is the process of manufacturing proteins, is discussed in
Chapter 2.

DNA
More than 99% of the human body's DNA is in the nucleus. This DNA is termed nuclearDNA. Cell
mitochondria also contain a small amount of DNA called mitochondrialDNA (mtDNA). This is discussed
in Chapter 3.
6 Unit I Basic Concepts From Molecular Genetics

DNA Structure
The basic structure of DNA is a set of four nucleic acids. These nucleic acids are nitrogen-containing compounds
made in part from the individual amino acids derived from the proteins we eat. Because these elements are the
basic structure of DNA, they are called bases. These four bases are adenine (A), cytosine (C), guanine (G),
and thymine (T) (Fig. 1-4). Thymine and cytosine are single-ring strucrures known as pyrimidines. (Memory
hint: The words thymine and cytosine contain a Y, as does the word pyrimidine.) Adenine and guanine are
both double-ringed structures known as purines. (Memory hint: The words adenine, guanine, and purine do
not contain a Y) These four bases are present in the DNA of humans and other mammals, plants, bacteria,
and viruses.
Each base becomes a nucleoside when a five-sided sugar (known as a deoxyribosesugar) is attached to it (see
Fig. 1-4). Each nucleoside becomes a complete nucleotide when a phosphate group is attached The nucleotide
is the final form of a base that is placed into the DNA strand. The nudeorides within each strand are held in
position by the linked phosphate groups, which act like the string holding beads together to form a necklace.
Base pairs are the complementary bases in the twO strands of DNA. These DNA strands must remain
perfectly parallel to each other, and the pairings of the nucleotides make this happen. For double-stranded
DNA (dsDNA) to remain parallel, the twO strands must Stay the same distance apart down the total length of
DNA. A pyrimidine with a single-ring Structure always pairs up with a purine that has a double-ring structure
to maintain this proper distance (see Fig. 1-4). Not only must a purine always pair with a pyrimidine, but
the bases are also always specific, forming complementary pairs.
Normally, adenine and thymine always pair together, and cytosine and guanine always pair together
(Fig. 1-5). The reason for these specific and complementary pairings of bases is related to the forces that hold
the twO DNA strands together. The twO strands are held together loosely most of the time by weak hydrogen

T-A complementary base pair

I

One nucleoside -------;

(a base with its
deoxyribose
sugar attached)

One nucleotide ----

(a base with its
CoG complementary
deoxyribose
base pair
sugar and
phosphorus
attached)

Figure 1-4 Four bases arranged as nucleotides in complementary base pairs. A == adenine,
C == cytosine, G == guanine, T == thymine, DR == deoxyribose, P == phosphorus.
 Chapter 1 DNA Structure and Function 7

Linear and straight complementarystrands

Figure 1-5 Double-stranded (ds) DNA arranged as

complementary strands in a linear structure and a
loose double helix. T = thymine, A = adenine, C =
Same strands arrangedin a loose doublehelix cytosine, G = guanine.

bonds. Importantly, these weak bonds allow the (WO strands to separate easily during cell division when the
DNA is to replicate. This separation does not require a 10[of energy and can occur quickly. Within a base
pair, the hydrogen bonds form between the rwo nucleorides. Adenine and thymine each have a site for (WO
hydrogen bonds to form, whereas cytosine and guanine each have three sites for hydrogen bonds to form (see
Fig. 1-4). Although purines must always pair with pyrimidines. they can pair only with the base that can form
the same number of hydrogen bonds. Thus, under normal conditions, adenine can pair only with thymine,
and cytosine can pair only with guanine.
As mentioned, DNA in humans and other mammals is a linear, double-stranded structure with the nucleo-
tides of each strand connected by the phosphate groups as the backbone of the strand (see Fig. 1-4). These
two individual strands are held together loosely by hydrogen bonds. In this way, dsDNA is arranged like a
long set of railroad tracks. The long steel rails of the track are the phosphate backbones, and the bases of the
nucleotides are each half of the individual railroad ties (Fig. 1-6).
Complementary base pairs in DNA are specific because adenine normally pairs with thymine, and cytosine
normally pairs with guanine. This means that if the base sequence of one strand of DNA is known, the opposite
strand's sequence can be predicted accurately. For example, the left-hand strand of DNA in Figure 1-6 has
the sequence T-G-G-C-A-T-T-G from tOp to bottom. and the corresponding (complementary) right-hand
section has the sequence A-C-C-G-T-A-A-C. Except during cell division. the two parallel strands of DNA are
twisted into a loose helical shape (see Figs. 1-2 and 1-5). The DNA supercoils rightly into the chromosome
shape (which is visible with standard microscopes) only when a cell undergoes mitosis.
Billions of bases are found in the DNA of just one cell. In its most common shape, DNA can be seen
only by using an electron microscope; however. if the DNA of one cell could be pur together and stretched
OUt, it would be about 6 feet long. If this same piece of DNA from one cell could be made about a half-inch
wide, it would stretch out more than 1,000 feet! Each nucleus contains much more DNA than is needed
for the 20,000 to 25,000 genes. The gene part of the DNA is only about 5% of all the total DNA in each
cell's nucleus, with the remaining DNA (called noncoding DNA) playing various roles in regulating gene
expressIOn.
8 Unit I Basic Concepts From Molecular Genetics

Complementarybase pairs
(railroadties)
3' 5'
~

Figure 1-6 An 8-base-pair segment of double-stranded (ds) DNA

similar to a section of railroad track. Phosphatelinkages(rails)

DNA Replication
Cell Division
Every time a cell divides, DNA replication occurs, which is duplication or reproduccion of itself, resulting in
two identical sets of DNA. This is needed because every cime a cell undergoes mitosis, a duplicacion division
results in two new cells that are idencical both to each other and to the original cell (parent cell) that began
the mitosis, and each cell must have a complete genome. For the two new cells created from mitosis to be
identical to the parent cell, the DNA of the parent cell must replicate exacrly. Mitosis occurs in a regulated
pattern known as the cell cycle. Figure 1-7 shows the phases of the cell cycle, which starts with one cell and
ends with two new cells. When mitosis is normal and the parent cell divides correcrly, each new cell has the
identical (and correct) amount of DNA and genes.
Cells not actively dividing are in a reproduccive rescing state known as Go- In this state, the cell is accively
performing its specific funccions but is not reproducing. For example, skin cells in the Go state produce keratin
and other skin products but do not reproduce. Normal cells are in the state of Go most of the time and leave
it only to reproduce when generacion of more cells is needed. To undergo mitosis, a cell first must be a cell
type capable of cell division. Some cells do nor divide once organ maturation is complete. Examples of these
nondividing cells include skeletal muscle cells, cardiac muscle cells, and neurons. If a cell has retained the
ability to divide when needed (e.g.. skin celis, bone marrow cells, liver cells, and epithelial cells that line most
organs), it will respond to signals to leave Go and enter the cell cycle. The cell cycle involves four phases.
Movement through these phases for successful generation of two new cells requires selective gene input. The
actions of these promitosis genes are discussed in Chapter 3. The acciviciesoccurring at each stage of the cell
cycle are outlined in Table 1-1.
 Chapter 1 DNA Structure and Function 9

DNA Synthesis
Generating twO new cells from one parent cell requires twice the DNA present in the parent cell. Notice in
Figure 1-7 that the nucleus during S phase is twice as large as it was during G. because it now has twice as
much DNA. This replication of the DNA ensures that the two new cells resulting from mitosis will each have
the same amount of DNA as the parent cell. The parent cell doubles its DNA content by DNA replication
in S phase. (Memory hint: S phase stands for synthesis of DNA.) To distinguish between the related concepts
of DNA replication and DNA synthesis, recall that DNA synthesis is the process of manufacturing DNA,
whereas DNA replication is synthesis resulting in two identical strands-an original and a replica, or copy.
One point to remember about human cellular DNA is that the complete genome within anyone cell is
not present as one very long double strand of DNA. Instead, there are 46 separate sets of dsDNA correspond-
ing to the 46 chromosomes (see Fig. I-I).These 46 metaphase chromosomes represent the 46 loosely coiled
double helices mat are not visible with a standard microscope.

G1 Phase

S Phase

G2 Phase

M Phase

Figure 1-7 Phases of the cell cycle for a cell undergoing mitosis.
10 Unit I Basic Concepts From Molecular Genetics

.'!.1:J.::aIl!!lii!
Activities of the Cell Cycle
Cell Cycle Phase Activities/Purpose
G, Cell prepares for division by taking on extra nutrients, making more
energy, and growing extra membrane
Amount of cell fluid (cytoplasm) also increases
S DNA replication and synthesis
G2 Production of proteins important to cell division and to normal physiologic
function after mitosis is complete
M Mitosis in which the DNA in the nucleus pulls apart and creates two nuclei
(nucleokinesisl. followed by the cell separating into two cells, each with
one nucleus (cytokinesis)

DNA replication begins when the individual sets of dsDNA separate by breaking the hydrogen bonds
holding the two strands in the double-helix form (Fig. 1-8). Once they separate, enzymes at each end of the
strands read the sequence of the original strands and build two new strands that are complementary to the
original strands. DNA must be "read" in one direction to correctly place the new nucleotides during DNA
synthesis, JUStas written languages must be read in only one direction to make sense. These strands are read
from the 5' (' stands for "prime") end of the DNA to the 3' end (these numbers refer to the specific carbon
on the sugar molecule that connects with the phosphorous molecule). Because new bases can only be added
at the 3' end, building or reading from 5' to 3' is termed downstream, and reading from 3' to 5' is termed
upstream. At the end of DNA replication, rwo new sets of dsDNA representing each of the 46 chromosomes
are present in the cell. Each new set of dsDNA contains one strand of the original dsDNA and one newly
synthesized strand (Fig. 1-9). Because each of the two new sets of dsDNA contains one of the original strand,
this type of DNA synthesis is known as the semiconseruatiue model of DNA replication.
Thus, new complementary strands are synthesized along the old strands, using the old strands as a model
or template to place each new complementary base in the proper order. We tend to think that the new
strand is built in a continuous fashion, starting at one end and proceeding to the other. Such a process would
be very slow, taking weeks, which is not compatible with Lifeas we know it. Imagine building a 300-mile
(SOO-kilometer) road with construction beginning only at one end and proceeding at the rate of 2 miles
(1.2 kilometers) per year, taking about 150 years to complete. Instead, road construction starts at many places
at the same time so that only a few years are needed to complete it. In the same way, to make the process of
replication efficient and rapid (seconds to minutes), DNA synthesis begins at multiple SPOtSsimultaneously
within each set of separated DNA strands. This allows many thousands of DNA areas to be replicated at the
same time. When replication is complete, the individual newly synthesized pieces are then linked together as
a continuous strand.
Many enzymes are involved in DNA synthesis, and these enzymes have different activities important to
correct DNA replication. Some of these enzyme functions include the following:
• Relaxing and unwinding the DNA helix
• Breaking the hydrogen bonds of dsDNA and separating it into two single strands (ss) of DNA (ssDNA)
• Keeping the ssDNA separate
• "Reading" the original DNA strands and determining the base order for the new strands
• Placing the nucleorides in the order specified by the template strand
 Chapter 1 DNA Structure and Function 11

Breaking of hydrogen bonds and separation

of a section of original ds-DNA at the
beginning of DNA replication

Strand separation is --_ .........

followed by enzymes
reading the original strands
and starting to build
complementary strands

A section of double-stranded
DNA just before DNA replication
Figure 1-8 A section of double-stranded (ds) DNA during breaking of hydrogen bonds and separation
of the dsDNA at the beginning of DNA replication and the building of new complementary strands.

• Linking the separate pieces of newly synthesized DNA into a conrinuous strand
• "Spell-checking" the new strands of DNA to ensure that each base in the new strand is complementary
to its base pair on the original strand
Table 1-2 lim some of me differem enzymes and their roles in the DNA replication process.

Chromosomes
After the DNA has completely replicated, 46 chromosome structures develop as rightly packed forms of DNA
during the metaphase (M phase) of mitosis in the cell cycle. During M phase, one complete set of DNA moves
into one of the rwo new cells made during mitosis, and the second complete set moves into the oilier new
cell. Thus, the rwo new cells each have the right amount of DNA with all the genes. The correct movement
of the DNA into the twO new cells requires that the 46 separate chunks of DNA twist very tightly, forming
12 Unit [ Basic Concepts From Molecular Genetics

Two original
complementary
ds-DNA strands
before DNA
replication

New sets of ds-DNA, each retaining one

single strand from the original ds-DNA
Figure 1-9 The semiconservative model of DNA replication in which the two new sets of double-stranded (ds)
DNA each retain one of the original strands.
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