Full text of DOI:10.1097/00002820-200110000-00006

© 2001 Lippincott Williams & Wilkins, Inc., Philadelphia
Lindsay A. Middelton, RN, CGC
Kathryn F. Peters, MS
Genes and Inheritance
K
E
Y
W O R D S
The information gained from the Human Genome Project and related genetic
research will undoubtedly create significant changes in healthcare practice. It is
becoming increasingly clear that nurses in all areas of clinical practice will
require a fundamental understanding of basic genetics. This article provides
the oncology nurse with an overview of basic genetic concepts, including
inheritance patterns of single gene conditions, pedigree construction, chromo-
some aberrations, and the multifactorial basis underlying the common diseases
of adulthood. Normal gene structure and function are be introduced and the
biochemistry of genetic errors is described
Genes
Chromosomes
Pedigree
Mutation
Inheritance
standing of these concepts will allow the oncology nurse to bet-
ter assess the current and future needs of patients with cancer.
Ⅵ Introduction
e are entering a new age in healthcare Almost weekly,
reports are printed in scientific journals, magazines,
and local newspapers announcing the discovery of a
Ⅵ Introduction to Chromosomes,
Genes, and Deoxyribonucleic Acid
W
new gene or genetic predisposition for a disease or physical
trait. These reports are exciting, because they provide new
insights into and hope for improved methods of diagnosis and
treatment modalities for the many children and adults affected
with genetic disorders, such as cystic fibrosis, Huntington dis-
ease, and muscular dystrophy. These reports also suggest that
common diseases, such as colon and breast cancer, which affect
many more individuals, are at least partially the result of alter-
ations in an individual’s genetic material (genome).
Consequently, it is imperative for oncology nurses to have a
basic understanding of genetic concepts, including patterns of
inheritance, pedigree construction, chromosome structure and
types of aberrations, structure and function of genes, mechanisms
for mutation, and methods of genetic testing. A basic under-
Genes are the instructions that direct the development of the
structure of the human body and its organs and direct how our
body functions. In the nucleus of each cell, there are 2 copies
of each of the 25,000—35,000 different genes (Fig. 1). In the
nucleus of each cell, groups of genes are packaged together on
microscopic structures called chromosomes. Twenty-two pairs
of chromosomes, numbered 1 to 22, are referred to as the
“autosomes.” The twenty-third pair comprises the sex chro-
mosomes. Deoxyribonucleic acid (DNA) is the chemical sub-
stance of which genes are made. As there are 2 copies of each
chromosome, there are 2 copies of each gene; 1 from the father
and 1 from the mother. Genes are passed from parents to chil-
From the Urologic Oncology Branch, National Cancer Institute, National
Institutes of Health, Bethesda, Md, and the Department of Biobehavioral
Health, Pennsylvania State University, University Park, Pa.
Address correspondence and reprint requests to: Lindsay A. Middelton,
National Cancer Institute/UOB, National Institutes of Health, 10 Center Dr,
MSC 1873, Bethesda, MD 20892.
Accepted for publication June 15, 2001.
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 357

processes. This family was referred to a geneticist and
was subsequently diagnosed with a cancer syndrome
called von Hippel-Lindau syndrome. Each of the
affected individuals had been diagnosed and treated at
separate institutions. The diagnosis of von Hippel-Lin-
dau syndrome might have been made much earlier had
healthcare providers involved in the family’s care taken a
3-generation family medical history and documented the
pedigree. After the diagnosis of von Hippel-Lindau syn-
drome, Dan’s father, Robert, was determined to have
bilateral renal tumors. A rigorous surveillance regimen
was initiated for 2 at-risk cousins with hypertension.
Figure 1 ꢀ Inside the cell.
In addition to improving the detection of hereditary cancer
syndromes and identification of family members who might ben-
efit from a surveillance program, construction of a pedigree pro-
vides an opportunity to build or enhance rapport with patients.
By carefully listening to how a patient responds to the medical
history questions for each family member, a nurse may assess the
social relationship of the patient to the nuclear and extended
family members. This appraisal often identifies psychosocial
issues within the family and offers opportunities for intervention.
In summary, the pedigree is a pictorial description of the family
structure and provides the family medical history in such a man-
ner that can be quickly accessed by all oncology healthcare
providers throughout the care of a patient and his or her family.
dren via the egg and sperm at conception. Each parent con-
tributes half of his or her child’s genes.
Historically, mutations in the instructions encoded by a
gene were believed to cause specific genetic disorders. How-
ever, research has shown that the line between having an
altered gene that causes disease and having an altered gene that
leads to a susceptibility to disease is becoming increasingly
blurred. It is through exploration of the health problems
within a patient’s extended family that one can identify poten-
tial health risks for the patient. Nurses may more readily iden-
tify patients at risk for familial cancer syndromes by construct-
ing an expanded family medical history.
Ⅵ Basic Construction of the Pedigree
Ⅵ Expanded Family History
An extended family history usually consists of information
about the patient, his or her children, the patient’s siblings, par-
ents, aunts/uncles, and grandparents. As shown in Fig. 2, circles
in the diagram represent females, squares represent males, and
diamonds represent individuals for which the gender is
unknown. When a diamond encloses a number, this number
represents the number of individuals of that gender. An arrow
identifies the patient. Information, such as name, date of birth,
cancer history, and other medical problems about the various
family members, is noted below each symbol. A diagonal line
through a symbol signifies that the represented person is
deceased. A single horizontal line between 2 symbols represents
a marital or otherwise permanent relationship. A vertical line
attached to the marital line at the top and the horizontal sib-ship
line at the bottom represents the line of descent. Symbols (cir-
cles, squares, and diamonds) attached to the sib-ship line repre-
sent the children of the couple. The symbol for each child is
attached to the sib-ship line with an individual vertical line. A
shaded or solid symbol represents an affected individual. Often
to condense a pedigree, nonbiologically related individuals may
not be displayed. Pedigrees throughout the rest of this series will
introduce you to other common symbols.
An expanded, three-generation family medical history in a
pedigree format is an invaluable tool for an oncology health-
care provider concerned not only about the identification of
health risks for his or her patient but also about the health sta-
tus of the entire family. Nurses already have the advanced clin-
ical assessment skills and family systems approach necessary to
complete this task. The pedigree enables the medical history to
be easily assessed and synthesized by the nurse and the entire
healthcare team. Often, it is not until a pedigree is taken that
the underlying basis for cancer in a family comes to light.
A cerebellar hemangioblastoma was diagnosed in a 28-
year-old man, Dan, followed by the development of reti-
nal angiomas 2 years later. Because of the unusual combi-
nation of the tumors at Dan’s age, his neurologist explored
an expanded family history. Dan reported that his brother,
Gary, also had been diagnosed with a cerebellar heman-
gioblastoma 6 months earlier. Further queries revealed
that Dan’s aunt, Mary, died at 37 years of age from renal
cell cancer, and his aunt, Pam, had 2 retinal tumors, and
was informed by her doctor that her hypertension was due
to excessive adrenaline. Dan’s grandfather, Milton, died at
age 37 from problems secondary to hypertension and had
a history of severe headaches.
Ⅵ Categories of Genetic Conditions
By constructing a 3-generation family medical history
in pedigree format (Fig. 2), it became evident that multi-
ple family members developed, at young ages, a variety
of tumors, some of which were due to malignant
Modern genetics traces its roots to 1865, with the publication
of a paper by the Austrian monk, Gregor Mendel. Like many
358 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters

Figure 2 ꢀ Von Hippel-Lindau family pedigree.
reports of scientific breakthroughs, the paper remained in
obscurity for many years, but since its rediscovery decades
later, there has been an explosion of information about the
inheritance of genetic conditions.
located on chromosome 15. An individual must have 2 copies
of the altered gene to be affected. Parents of children with
Bloom syndrome “carry” 1 copy of the altered gene and 1
normal copy of the gene. Carriers of the altered gene copy are
usually asymptomatic, with no known increased risk for can-
cer or other health problems. With each pregnancy, carriers
have a 50% (1 in 2) chance of passing the altered gene copy to
their child.
There are 3 primary categories of genetic conditions: single
gene (Mendelian), chromosomal, and multifactorial. Conditions
that are categorized as “single gene” are conditions caused by a
mutation or alteration of a single gene. This category is further
delineated as following either an autosomal dominant, autosomal
recessive, or X-linked recessive inheritance pattern. Recall the
term autosomal refers to conditions that are caused by mutated or
altered genes carried on one of the chromosome pairs 1 to 22
(autosomes). Genetic conditions that follow an X-linked reces-
sive pattern of inheritance are caused by gene alterations located
on the X-chromosome. Conditions categorized as chromosome
abnormalities involve an entire or a significant portion of a chro-
mosome, composed of many genes. Finally, conditions catego-
rized as multifactorial are due to the inheritance of 1 or more
mutant genes interacting with the environment, other genes, or
other factors to produce the trait or disease.
Thus, each child of parents who are carriers of an autosomal
recessive condition has:
• a 25% (1 in 4) chance of being affected.
• a 50% (1 in 2) chance of being a carrier and unaffected.
• a 25% (1 in 4) chance of neither having the disorder nor
being a carrier.
These recurrence risks are independent of the sex of the
child. That is, men and women may be affected by autosomal
recessive conditions. Following is a pedigree characteristic of a
family with Bloom syndrome (Fig. 3).
When considering if an individual is affected with an autoso-
mal recessive condition, it is often helpful to know the ethnic
background of the individual’s parents. Although it is estimated
that each person, regardless of ethnic background, carries 10 to
15 mutated genes, the frequency of carriers of gene mutations
for some disorders is known for a few specific ethnic groups. For
example, approximately 1% (1 in 100) of individuals of Ashke-
nazi Jewish ancestry are carriers of Bloom syndrome.
It is also helpful to know if the parents are biologically
related (consanguineous). In general, parents who are biologi-
cally related have a higher chance of carrying a copy of the
same altered gene than 2 unrelated individuals. For example,
first cousins have a 12.5% (1 in 8) chance of carrying the same
Single-gene Conditions:
Autosomal Recessive
Bloom syndrome is an autosomal recessive genetic condition
characterized by leukemia, susceptibility to infections, skin
cancer, and short stature. It is common for the parents of a
child newly diagnosed with Bloom syndrome to respond with
the statement, “But, there is no one in our family with it. How
can it be genetic?”
Bloom syndrome is “genetic” because it is caused by the
inheritance of 2 copies of an altered or nonworking gene
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 359

Figure 3 ꢀ Autosomal recessive
pedigree: Bloom syndrome.
mutated gene. Consequently, consanguineous couples have an
increased risk for having a child with an autosomal recessive
genetic condition. However, it is important to remember that
a couple need not be related nor of a certain ethnic back-
ground to have a child affected with an autosomal recessive
condition. Individuals of all ethnic backgrounds and of unre-
lated parents may be affected with autosomal recessive condi-
tions. Examples of other autosomal recessive genetic disorders
with an increased risk of cancer are xeroderma pigmentosum
and Fanconi anemia.
• a 50% (1 in 2) chance of inheriting the altered (nonwork-
ing) gene and being affected.
• a 50% (1 in 2) chance of inheriting the unaltered (working)
gene and not being affected.
Gender has no bearing on whether a child will be affected
by an autosomal dominant condition. That is, men and
women may be affected. Fig. 4 shows the pedigree of a family
with neurofibromatosis, type 1.
Some types of breast and ovarian cancer appear to have an
autosomal dominant pattern of inheritance, but because breast
cancer is common, it can be difficult to distinguish between an
individual who is affected due to the inheritance of an altered
gene and an individual who is sporadically affected.
Single-gene Conditions: Autosomal Dominant
It is becoming more and more common to hear from individ-
uals with cancer that there are other members of their families
affected with the same type and/or other types of cancer. In
many cases, this may be due to chance or to shared environ-
ment, but in others, further elucidation of the extended fam-
ily history will reveal a family affected with a heritable cancer
syndrome.
Examples of genetic conditions with a predisposition to
cancer that follow an autosomal dominant pattern of inheri-
tance are neurofibromatosis, tuberous sclerosis, von Hippel-
Lindau, and hereditary nonpolyposis colorectal cancer. Not
all individuals with these autosomal dominant genetic disor-
ders develop cancer, but all have a predisposition to and an
increased risk of cancer. Unlike autosomal recessive condi-
tions, an individual with an autosomal dominant genetic
condition needs only to have one mutated gene to be
affected. Each child of an individual who has an autosomal
dominant genetic condition has:
Single-gene Conditions: X-linked
In some cases, the gender of an individual does have relevance
to whether he or she will be affected with a specific genetic
condition. For example, Wiskott-Aldrich syndrome is a
genetic condition characterized by small abnormal platelets,
thrombocytopenia, and abnormal immunoglobulin levels.
This condition preferentially affects males, because it is caused
by an alteration of a gene carried on the X-chromosome and
follows the X-linked recessive pattern of inheritance.
Recall, men and women have 2 copies of autosomes (chromo-
somes 1 to 22). However, men and women differ in their sex
chromosomes. Females have 2 X-chromosomes, whereas males
have 1 X-chromosome and 1 Y-chromosome. For the most part,
the genes on the X-chromosome differ from those on the Y-chro-
mosome. Thus, men have only 1 copy of each of the genes car-
360 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters

All the daughters of a man affected with an X-linked genetic
condition will be carriers of the condition, but generally will
be unaffected. His sons will not be carriers of, nor affected by
the condition. An affected father can never pass the X-linked
recessive condition to his son. Thus, one feature that distin-
guishes the X-linked recessive pattern of inheritance from the
other patterns of inheritance is the absence of male to male
transmission. Fig. 5 demonstrates a pedigree characteristic of a
family with Wiskott-Aldrich syndrome.
Ⅵ Chromosomal Disorders
The second category of genetic conditions involves chromoso-
mal aberrations–associated disorders. The field of cytogenetics
is the study of chromosomes and how they are transmitted
from parents to their offspring. A single chromosome consists
of a tightly coiled and compacted strand of DNA, which is
made up of hundreds to thousands of functional genes. A large
percentage of chromosomal DNA does not encode genes; its
role is not completely understood. In other words, a strand of
DNA is not comprised of genes lying next to one another but
more like beads on a string with spacer material between the
functional genes.
Recall, individuals typically have 23 pairs of chromosomes; 1
of each pair is inherited from the mother’s egg and the other pair
is inherited from the father’s sperm. Chromosomes are desig-
nated by number according to their size and shape. Chromosome
1 is the largest, and chromosome 22 is one of the smallest. As
stated, chromosome pairs 1 to 22 are called autosomes and the
23rd pair consists of the sex chromosomes. Men have an X and a
Y chromosome, and women have two X chromosomes (Fig. 6).
Human chromosomes consist of a short and long arm sepa-
rated by an area of constriction known as the centromere. The
short arm of the chromosome is referred to as the p-arm, and
the long arm of the chromosome is referred to as the q-arm.
Therefore, the designation 8q refers to the long arm of chro-
mosome 8. In the laboratory, chromosomes can be stained to
reveal alternating light and dark horizontal bands. These bands
assist in the identification of individual chromosomes, because
the banding pattern is unique to each chromosome. The bands
also can serve as geographic landmarks for localization of
genetic markers and genes. In the cytogenetic laboratory, the
chromosomes are stained and analyzed for number, structure,
and missing (deleted) or additional (duplicated) genetic mate-
rial. A karyotype is a picture of the chromosomes produced by
taking a photograph and cutting out each of the 46 chromo-
somes and lining the pairs together. By convention, the chro-
mosomes are arranged so that the short arm is on top and the
long arm is the on the bottom and in descending order of size.
There are 2 main classes of chromosome anomalies: abnor-
mal chromosome number (aneuploidy) and structural
rearrangements. The usual process by which an individual pos-
sesses an abnormal chromosome number in every cell is due to
an error occurring during meiosis. Meiotic cell division is the
process by which the sperm and egg receive one half of the
genetic material, or 23 chromosomes. At conception, the
Figure 4 ꢀ Autosomal dominant pedigree: neurofibromatosis.
ried on the X-chromosome, whereas women have 2 copies. A
deleterious mutation in a gene on the X-chromosome will always
be expressed in men, because they only have one copy of each of
those genes. They do not have a working copy of the gene on a
second X-chromosome. An alteration in a gene on 1 of the 2 X-
chromosomes in a female generally produces no symptoms,
because the unaltered, or working, gene on the second X - chro-
mosome compensates for the mutated gene’s effects.
The mother of a boy affected with Wiskott-Aldrich syn-
drome or any other X-linked recessive genetic condition may
be a carrier of the condition or the child may be affected as a
result of a new mutation. A male child inherits his X chromo-
some only from his mother and his Y chromosome only from
his father. With each pregnancy, women who are carriers of a
deleterious mutation on one of their two X chromosomes face
the following possible outcomes:
With each pregnancy, women who are carriers of a deleteri-
ous mutation on one of their two X chromosomes face the fol-
lowing possible outcomes:
• 50% (1 in 2) chance that a son will inherit the X chromo-
some with the altered (nonworking) gene and be affected.
• 50% (1 in 2) that a son will inherit the X chromosome with
the unaltered (working) gene and not be affected.
• 50% (1 in 2) chance that a daughter will inherit the X chro-
mosome with the altered (nonworking) gene and be a car-
rier, but unaffected.
• 50% (1 in 2) chance that a daughter will inherit the X chro-
mosome with the unaltered (working) gene and be neither a
carrier, affected, nor at risk for having an affected son.
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 361

Figure 5 ꢀ X-linked recessive pedi-
gree: Wiskott-Aldrich.
sperm and egg fuse to produce a fertilized egg with the restored
number of 46 chromosomes.
years are offered prenatal diagnosis by amniocentesis or chori-
onic villus sampling to detect changes in chromosome number.
For couples that have a child with chromosomal aneuploidy, the
chance of having another child with an abnormal number of
chromosomes is slightly (0.5% to 1.0%) higher than would be
expected based on the mother’s age. This recurrence risk is based
on empiric data rather than on a specific mode of inheritance.
Aneuploidy does not transmit in Mendelian patterns of inheri-
tance observed in single-gene disorders.
Chromosome instability is another mechanism in which
individual cells acquire or lose chromosomes. Chromosomal
instability in tumors leading to the gain or loss of whole chro-
mosomes, or portions thereof, will be addressed in the next
module.
Ⅵ Aneuploidy
Aneuploidy is generally the result of errors in meiotic cell divi-
sion before the time of conception, creating a sperm or egg
with too many or too few chromosomes. This abnormal chro-
mosome number is passed on to the child at conception. The
most common chromosome disorder in live born infants is
Down Syndrome, also referred to as Trisomy 21. As the genetic
name implies, the majority of the individuals with Down Syn-
drome have 3 copies of chromosome 21 (Fig. 7). This syn-
drome is characterized by typical physical features, mild to
severe mental retardation, and an increased risk for other
health problems, including congenital heart disease, thyroid
dysfunction, and leukemia.
Ⅵ Structural Rearrangements
Other examples of aneuploid chromosomes include Trisomy
13 and Trisomy 18, often-lethal disorders of neonatal life.
However, some children with these 2 types of trisomies survive
with significant physical disabilities and mental impairment.
Individuals who have 1 too many or 1 too few chromosomes
either have an extra set of every gene on that chromosome or
lack an entire set of genes from the missing chromosome.
Because of this large number of additional or missing genes,
there are few aneuploid situations that are consistent with a
normal lifespan or without major health problems.
Another class of chromosomal errors is the structural
rearrangement of one or more chromosomes. Several types of
structural abnormalities are observed, but the most common
abnormality involves the breaking and rearrangement of 2 or
more chromosomes. In these situations, usually 2 chromo-
somes break somewhere along their length and the free chro-
mosome pieces exchange places. This is referred to as a recip-
rocal translocation (Fig. 8). If the chromosomal break occurs
in a section of the DNA that does not contain a structural gene
and there is no gain or loss of chromosomal material (balanced
translocation), there most likely will be no impact on the
health of the individual. However, such a rearrangement does
The risk of having a child with chromosomal aneuploidy
increases with maternal age. Women older than the age of 35
362 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters

Figure 6 ꢀ Normal female
karyotype (courtesy of Cyto-
genetics Laboratory, Depart-
ment of Obstetrics and
Gynecology, Georgetown
University Medical Center,
Washington, DC).
result in an increased risk of pregnancy loss. Approximately 1
in 500 to 1,500 persons carry a balanced translocation. When
carriers of balanced translocations conceive, the child may
receive an unbalanced amount of chromosomal material,
resulting in an increased risk of miscarriage or a child with
physical and/or mental abnormalities.
Multifactorial inheritance is believed to be the basis for
most, if not all, of the common chronic diseases of adulthood
such as diabetes, essential hypertension, multiple sclerosis,
coronary artery disease, and cancer, as well as some of the com-
mon isolated birth defects of childhood including cleft
lip/palate, congenital heart disease, and neural tube defects. It
has long been observed that these conditions can occur in
more than one member of an extended pedigree but do not
follow clear Mendelian inheritance patterns.
Chromosomal breaks can occur in critical regions of a chro-
mosome with disruption of gene function due to loss (dele-
tion) or gain of critical genetic material. Translocations also
can cause problems by placing one critical gene next to or
within another critical gene. In these situations, the location or
combination of the 2 gene sequences may promote oncogene-
sis. One of the earliest known relationships between a chro-
mosomal translocation and cancer was the reciprocal translo-
cation between chromosomes 22q and 9q found in the bone
marrow of 95% of adults with chronic myelogenous leukemia
(Fig. 9). This translocation places the c-abl oncogene from
chromosome 9q next to the breakpoint cluster region (bcr) on
chromosome 22q. The juxtaposition of these 2 genes enhances
the growth-promoting properties of c-abl oncogene, which
predisposes the cells to undergo malignant transformation.
Ⅵ Multifactorial Inheritance
The third category of genetic conditions is one in which dis-
orders are attributed to an interaction between one or more
genes (polygenic) or between one or more genes and environ-
mental influences. Genes do not function in isolation but in
concert with other genes and are influenced by the surround-
ing environment. Most human traits are determined by the
interaction of many genes and environmental influences rather
than the function of a single gene. When environmental fac-
tors are known to influence the expression of a genetic trait or
disease, the term multifactorial inheritance is used.
Figure 7
ꢀ Trisomy 21 karyotype (courtesy of Cytogenetics
Laboratory, Department of Obstetrics and Gynecology,
Georgetown University Medical Center, Washington, DC).
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 363

Figure 9 ꢀ Schematic model of the Philadelphia chromosome.
From Thompson JS, Thompson MW. Genetics in Medicine. 4th
ed. Philadelphia: WB Saunders; 1986. Used with permssion of
W.B. Saunders Company.
Figure 8 ꢀ Reciprocal translocation and its consequences.
From Thompson JS, Thompson MW. Genetics in Medicine. 4th
ed. Philadelphia: WB Saunders; 1986. Used with permssion of
W.B. Saunders Company.
Variation in Gene Expression
As stated above, genes do not act alone, but are influenced by
the genetic background of an individual and by the external or
internal environment. A person’s genetic constitution, or
genome, is referred to as his or her genotype. How these genes
express themselves in height, hair color, body chemistry, etc.,
is referred to as his or her phenotype. There are several factors
that play a role in how a gene is expressed.
Variable expressivity and incomplete penetrance are features
observed frequently in heritable conditions and may also play
a role in genetic predisposition or susceptibility to common
diseases. An altered or mutated gene may not always be
expressed (incomplete penetrance) or, if expressed, may vary
widely in different individuals (variable expressivity).
Fig. 4 demonstrates a neurofibromatosis type 1 (NF1) pedi-
gree. NF type 1 is an autosomal dominant disorder character-
ized by neurofibromas (soft cutaneous nodules), café’au lait
spots (light brown, flat skin lesions), Lisch nodules (benign,
small tumors of the iris), and an increased risk of malignancy.
From analysis of this pedigree, it can be postulated that
Mary must carry the NF gene, because her father and son are
affected. However, she does not demonstrate clinical features
of the syndrome. Therefore, neurofibromatosis is considered to
be nonpenetrant in Mary. Some genetic disorders are highly
penetrant, meaning that if an individual has the gene in ques-
tion, he or she is highly likely to have clinical features of that
disorder. Conversely, there are some genetic disorders that have
decreased or low penetrance. In these conditions, if an indi-
vidual inherits the mutated gene in question, he or she may
not experience clinical features of the disorder. Penetrance of
genetic disorders varies from disorder to disorder and from one
family to another, and nonpenetrance is actually quite unusual
in NF, type 1.
Every individual has genes that predispose or increase suscep-
tibility to particular traits or disease. The presence of a predis-
posing gene, alone, does not result in the trait or disease but con-
fers susceptibility to that particular characteristic. The likelihood
of developing a disease or having a trait increases when a person
who possesses a predisposing gene also carries other genes that
influence the function of that gene or provides added predispo-
sition to that particular trait or disease. This risk is further
amplified when specific environmental influences are present.
An example of the interplay between genes and environ-
ment is presented in Fig. 10, which illustrates factors involved
in coronary artery disease. An individual who carries the poly-
genic traits of hypertension, obesity, or elevated cholesterol as
individual conditions may not be destined to develop coronary
artery disease. However, if that person possesses a major gene
for defective Apolipoprotein E metabolism and leads an
unhealthy lifestyle, the risk of coronary artery disease would be
substantially increased because of this combination of factors.
An understanding of the genetic and environmental contribu-
tions to the pathophysiology of a particular disease may lead to
more effective prevention, earlier detection, and specific, more
effective treatment modalities of these diseases. Many common
sporadic cancers follow a similar model of inheritance as coro-
nary artery disease.
Risks to other family members can often be provided with
confidence in single-gene inheritance; however, it is more dif-
ficult to assess the risk in multifactorial conditions. Identifying
the specific roles of multiple genes involved in a given condi-
tion and to elucidate the effects of a variety of environmental
influences is a daunting task. For most multifactorial diseases,
empiric risks are provided. Empiric risks are based on a collec-
tion of large population studies and may or may not reflect the
risks for a specific individual. Reliable empiric data are avail-
able for a few of the more common cancers such as breast and
colon, but not all cancers with a multifactorial etiology.
This family also demonstrates the phenomenon of variabil-
ity of expression, which is different from the phenomenon of
penetrance. The clinically affected members of this family all
have NF, but their clinical features vary in both their severity
364 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters

Figure 10 ꢀ Schematic for model of gene–environment inter-
actions. From McCante, Heuther, eds. Pathophysiology: the
biological basis for disease in adults and children. Copyright
1994 by Roger R. Williams. Used with permission of Mosby-
Year Book, Inc.
and organ(s) of involvement. Mary’s father, Chuck, has multi-
ple café au lait spots, has multiple disfiguring cutaneous neu-
rofibromas, and had abdominal surgery becuase of invasion of
a large neurofibroma within the peritoneal cavity. Marleen’s
only clinical features of neurofibromatosis are 15 café’au lait
spots and 1 Lisch nodule. Randy, Mary’s son, has clinical
symptoms consisting of multiple café’au lait spots and an
enlarging neurofibroma along the vertebral column. This pedi-
gree demonstrates reduced penetrance and variable expressiv-
ity. Variability of expression and penetrance are features more
commonly observed in autosomal dominant genetic disorders.
Ⅵ Molecular Biology:
Normal Structure of the Gene
A prerequisite for understanding the complexities of cancer
genetics and the nuances of genetic testing is a fundamental
knowledge of the anatomy and biochemistry of genes and
DNA. DNA must undergo replication, transcription, and
translation before producing protein as a final gene product.
The next few sections provide an overview of the basics of gene
structure and function. Genes are composed of DNA and
serve as instructions for cellular assembly of proteins. In 1953,
Watson and Crick identified the 3-dimensional double helix
structure of DNA, which provided an explanation of how
DNA replicates, or copies itself.
Figure 11 ꢀ DNA helix demonstrating replication of a new
DNA strand. From Watson, Tooze, and Kurtz. Recombinant
DNA: A Short Course. Copyright 1983 by James Watson,
John Tooze, and David T. Kurtz. Used with permission of W.H.
Freeman and Company.
Ⅵ Deoxyribonucleic Acid
Replication and Transcription
DNA is made up of 2 long, twisted strands. Each strand is
composed of smaller chemical units called nucleotides. Each
nucleotide is made up of 3 components: a sugar, a phosphate,
and a nitrogenous base. The sugar and phosphate molecules
bond tightly into 2 strands, providing the structural backbone of
DNA. The third component of the nucleotide is 1 of 4 nitroge-
nous bases: A (adenine), T (thymine), G (guanine), and C (cyto-
sine). The 2 DNA strands line up next to one another like 2 sides
of a zipper with the bases acting like interlocking teeth. The 2
sides of the zipper fit together in only 1 way: A always pairs with
T, and G always pairs with C (Fig. 11). The only shape that will
accommodate this exact matching of bases is the DNA helix.
Before cell division, a new DNA strand must be synthesized.
To do this, the 2 strands separate and unwind, with each
strand becoming a template for a new strand (Fig. 11). The
new DNA strand is produced by a protein celled DNA poly-
merase, which travels up the template strand, adding each
complementary nitrogenous base according to the template.
DNA polymerase also plays a role in maintenance and repair
of DNA, proofreading as it travels up the DNA template
strand. Human cells have a number of mechanisms for identi-
fication and repair of copy errors to improve the accuracy of
DNA replication. This way, each gene is faithfully replicated in
preparation for cell division.
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 365

Figure 12 ꢀ Transcription and
processing of a beta-globin gene
to form a mature messenger RNA.
From Thompson JS, Thompson
MW. Genetics in Medicine. 4th
ed. Copyright 1986 by James S.
Thompson and Margaret W.
Thompson. Used with permission
of W.B. Saunders.
DNA is formed and replicated in the cell nucleus, whereas
protein synthesis takes place in the cytoplasm of the cell. The
transportation of the genetic code from the nucleus to the cyto-
plasm and the interpretation of the code involves 2 basic
processes: transcription followed by translation. Ribonucleic
acid (RNA) is the nucleic acid involved in these 2 processes.
Similar in structure to DNA, RNA differs because it comprises
only 1 strand, and the nitrogenous base thymine (T) is replaced
by uracil (U). Transcription (Fig. 12) is the process by which
RNA is synthesized from the DNA template. Genes comprise
both coding (exons) and noncoding (introns) regions. Introns
are noncoding regions interspersed throughout most genes,
which are spliced out (removed) after transcription. This process
results in a mRNA (messenger RNA) transcript, which is free to
move out of the nucleus and into the cytoplasm.
This is accomplished by a cytoplasmic particle called the
ribosome, which reads the code and assembles the prescribed
amino acids, thereby constructing a complete polypeptide
(Fig. 14). Thus, each complex protein produced in our body
is a product; the production of which is directed, or coded,
by a gene.
Gene function and expression are influenced by regulatory
elements located either in vicinity to the gene or at some dis-
tance from the gene. Examples of regulatory elements are
enhancers, which upregulate or enhance gene expression, and
repressors, which down regulate or slow gene expression.
With this background of genetics, it is possible to consider
molecular pathology and how these errors relate to human
disease.
Ⅵ Molecular Biology: Mutations
Ⅵ Genetic Code
Genes are generally stable and are passed through generations
without change. However, genes occasionally change, and this
process is referred to as a mutation. The term mutation sug-
gests a negative consequence; however, mutations frequently
occur without health consequences. Genetic mutations are
most likely the explanation for evolutionary changes in our
species. Between the structural genes are long segments of non-
coding DNA with as yet unknown function. Within this DNA
are mutations or variations in nucleotide sequence, which have
no apparent phenotypic effects. These normal variations are
relatively frequent in the population and are referred to as
benign polymorphisms.
Mutations can occur in the germ line (sperm and egg) cells
or may occur in the somatic (body) cells after fertilization.
Much of the DNA is composed of sequences that do not code
for specific proteins, so that a change or alteration in these
noncoding regions often may not be detected. However, if a
mutation occurs in the coding sequence of a structural gene,
the final gene product, a protein, may not be formed correctly.
The protein may not be produced at all or the quantity/qual-
ity and function may be significantly altered. There are several
categories of mutations, the most frequent are point mutations
and frameshift mutations.
Genes direct the synthesis of all the body’s proteins. The body
contains 20 essential amino acids that assemble together in an
infinite number of ways to create the larger, more complex pro-
teins. In general, 3 nucleotides make up a triplet, called a codon.
Thus, an example of a codon is “CCG.” In general, each codon
specifies the production of one amino acid. Proteins, or
polypeptides, are then formed, made up of sequences of many
amino acids. Thus, each gene that codes for a complex protein
is composed of a series of codons, which act as instructions for
the building of a protein. The 4 letters of this code (A, T, G, and
C) are used to write an infinite combination of instructions for
thousands of proteins, which is called the genetic code (Fig. 13).
The codons are read sequentially from left to right in sequences
of triplets, thereby specifying the sequence of amino acids. The
division of bases into triplets that specify the amino acid
sequence of the protein is called the reading frame.
Ⅵ Translation
Translation is the process in which the codon sequence of the
RNA transcript is converted into a sequence of amino acids.
366 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters

Figure 13 ꢀ The Genetic Code.
bled protein is shortened. This is generally a useless protein
that is often degraded resulting in absence of the normal gene
product, which can lead to disease.
Point Mutations and Frameshift Mutations
Point mutations involve the substitute of 1 nitrogenous base
(A,T,G,C) for another. One can make an analogy to spelling
errors. Imagine a spelling error in which a simple typographical
error occurs. GTT may be “misspelled” ATT. This type of error
is a point mutation in which the nitrogenous base (G) is substi-
tuted by the nitrogenous base (A). In this example, the amino
acid, isoleucine, would be produced instead of valine. A base sub-
stitution may have either no detectable effect on the biologic
activity of a protein or may result in a protein product that has
no activity, reduced activity, or increased activity. This is why
some mutations are benign whereas others lead to disease. Point
mutations do not interrupt the reading frame of a gene. The
codons following the one in which a point mutation occurred are
not disturbed.
Codons can be interrupted by the insertion or deletion of a
single or multiple bases. In these situations, often a significant
change results in the amino acid sequence of the final protein
product. This is due to a change in the reading frame for all the
subsequent codons (frameshift mutation). In the example
shown in Fig. 15, a deletion of 1 base pair has occurred,
switching the reading of the codons from GCU to CUG.
Recall that uracil (U) replaces thymine (T) in the RNA tran-
script. In this example, the amino acid leucine replaces alanine
in the assembly of the final gene product, which is repeated in
subsequent codons. The function of the final protein product
is likely to have changed significantly.
Occasionally entire codons are eliminated. Cystic fibrosis
provides an example. The first mutation discovered to cause
cystic fibrosis was the deletion of 1 three-letter codon. There-
fore, the final protein produced is missing a single amino acid.
The absence of this single amino acid accounts for the spec-
trum of clinical problems faced by many CF individuals. Since
then, more than several hundred different mutations in the
cystic fibrosis gene have been identified, many unique to a sin-
gle family. Molecular laboratories today are not testing for all
known CF mutations, only the most common ones. There-
fore, a negative cystic fibrosis mutation test eliminates the
presence of the most common mutations, but cannot guaran-
tee that a person does not carry any of the hundreds of other
mutations that can cause cystic fibrosis. Similar problems have
been found in cancer susceptibility genes. More than 300
mutations have been identified in the BRCA1 gene.
Both point mutations and frameshift mutations may result
in a premature message to stop production of the polypeptide.
A polypeptide chain is assembled according to the codons
along the RNA transcript until a STOP codon is reached. If a
mutation in a codon for an amino acid results in a codon that
provides a premature message to stop translation, the assem-
Figure 14
ꢀ Translation of mRNA into a polypeptide chain.
From Thompson JS, Thompson MW. Genetics in Medicine. 4th
ed. Copyright 1986 by James S. Thompson and Margaret W.
Thompson. Used with permission of W.B. Saunders.
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 367

as linkage analysis. Known sequences of DNA (polymor-
phisms) near the gene of interest act as biologic markers that
can be tracked or followed from generation to generation. The
closer the known gene sequence (marker) is to the disease gene,
the higher the likelihood the person inherited the marker and
disease gene together. The farther the distance from the
marker, the greater the possibility that a meiotic crossing-over
event occurred. This possibility leads to a statement of proba-
bility that a member of a family might also have the disease
gene but not a definitive determination.
Figure 15
ꢀ Frameshift mutation schematic demonstrating a
Linkage analysis generally involves the testing of multiple
members of a family, offering the benefit of possible gene dis-
covery, but with the limitation of imprecise interpretation: link-
age analysis is most often used in the research setting, but is an
example of an indirect testing method, which should be familiar
to the oncology healthcare professional. There are many nuances
and complexities to genetic testing that will be addressed in
greater detail in a later series article. These complexities must be
understood by healthcare professionals because increasing num-
bers of genetic tests are becoming available resulting from the
Human Genome Project and genome-related research overall.
As we are continually faced with daily headlines reporting new
gene discoveries, we will face increasing interest from the public
in understanding potential uses of new gene tests.
normal sequence, an insertion of a single base, and a deletion
of a single base. The two frameshift mutations after the reading
frame and thus the amino acid composition of the final protein.
Ⅵ Molecular Genetic Testing
As genetic testing becomes increasingly used in the oncology
field, appropriate interpretation of genetic test results is essen-
tial, because people may base important life-altering decisions
on the information. To accomplish this, it is imperative that
healthcare providers have a basic understanding about the
structure and function of genes, mechanisms for genetic errors,
and genetic testing methods. Molecular genetic testing is
accomplished either by direct mutational analysis or by indi-
rect methods, each having different levels of sensitivity and
complexity. Direct testing can be done in situations in which
the precise gene mutation has been identified in an affected
individual. Finding an affected person’s mutation is generally
done by gene sequencing. When the precise mutation is iden-
tified in a family, at-risk family members may be tested specif-
ically for the presence or absence of that mutation. Direct test-
ing for the deleterious gene in these situations has a high
degree of accuracy when performed by an experienced molec-
ular laboratory. With the exception of one class of mutations,
most mutations are stable and will not change within and
among family members.
Indirect methods of genetic testing are less precise and
involve more complex interpretive analyses. Indirect testing
relies on identifying whether an individual has inherited a
region of a specific chromosome that contains a gene, rather
than looking for the precise gene mutation. During meiosis,
maternal and paternal chromosomes normally line up next to
one another, exchanging portions or segments. It is this normal
process of meiotic recombination that accounts for the unlim-
ited variation observed in humans, such that each individual is
entirely unique. It is also the basis for understanding linkage
analysis, an indirect method of genetic testing.
Ⅵ Human Genome Project
The information gained from the Human Genome Project
(refer to the first article in this series) will undoubtedly create
significant changes in healthcare practice. All human genes will
eventually be found, and accurate diagnoses will be developed
for most inherited diseases. In addition, animal models for
human disease research will be more easily developed, facilitat-
ing the understanding of gene function in health and disease.
Researchers have identified single genes associated with a
number of diseases such as neurofibromatosis, Duchenne mus-
cular dystrophy, retinoblastoma, inherited forms of breast and
colon cancer, and cystic fibrosis. As research progresses, inves-
tigators will also uncover the mechanisms for diseases caused
by several genes or by a gene interacting with environmental
factors. Genetic susceptibilities have been implicated in many
major disabling and fatal diseases, including heart disease,
stroke, diabetes, and cancer. The identification of these genes
and their proteins will pave the way for more effective thera-
pies and preventive measures. Investigators determining the
underlying biology of genome organization and gene regula-
tion will also begin to understand how humans develop from
single cells to adults, why this process sometimes goes awry,
and what changes take place as people age.
Ⅵ Linkage Analysis
Suggested Reading
1. Department of Health and Human Services: National Institutes of Health.
National Institute of General Medical Sciences. The New Human Genetics:
How Gene Splicing Helps Researchers Fight Inherited Diseases. Publication
No: 84.662. Washington, DC: Department of Health and Human Ser-
vices; 1984.
In many instances, before the discovery of a disease-causing
gene, testing involves localization of the gene to a particular
chromosome and then to a specific segment of that chromo-
some. This is accomplished through an indirect process known
368 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters

2. Roberts JAF, Pembroy ME. An Introduction to Medical Genetics. 8th ed.
Oxford: Oxford University Press; 1985.
McCarel KL, Huenther SE, eds. The Biologic Basis for Disease in Humans.
2nd ed. St. Louis: Mosby; 1994:166–201.
3. Lewin B. Genes V. New York: John Wiley and Sons; 1994.
4. Jorde LB. Genes and genetic disease. In: McCanrel KL, Huenther SE. eds.
The Biologic Basis for Disease in Adults. 2nd ed. St. Louis: Mosby;
1994:126–165.
6. Ellis NA, Roe AM, Kozloski J, Proytcheva M, Falk C, German J. Linkage
disequilibrium between the FES, DI5S127, and BLM loci in Ashkenazi
Jews with Bloom syndrome. Am J Hum Genet. 1994;55:453–460.
7. Bennett R, Steinhaus KA, Uhrich SB, et al. Recommendations for standardized
human pedigree nomenclature. Journal of Genetic Counseling. 1995:4:267–279.
5. Williams RR. Genes and environmental interaction: familial diseases. In:
This continuing nursing education (CNE) activity for 3.0 contact hours is pro-
vided by Lippincott Williams & Wilkins, which is accredited as a provider of
continuing education in nursing by the American Nurses Credentialing Cen-
ter’s Commission on Accreditation and by the American Association of Crit-
ical-Care Nurses (AACN 9722, Category O). This activity is also provider
approved by the California Board of Registered Nursing, Provider Number
CEP11749 for 3.0 contact hours. Lippincott Williams & Wilkins is also an
approved provider of CNE in Alabama, Florida, and Iowa and holds the fol-
lowing provider numbers: AL #ABNP0114, FL #FBN2454, IA #75. All of its
home study activities are classified for Texas nursing continuing education
requirements as Type I.
CONTINUING EDUCATION
ce
TEST 2.0 HOURS
To earn continuing education (CE) credit, follow these instructions:
1. Read the article on page 357. Complete sections A, B, and C* on the enroll-
ment coupon. Each question has only one correct answer.
2. Send the coupon with your $19.95 registration fee to: Continuing Educa-
tion Department, Lippincott Williams & Wilkins, 345 Hudson Street, New
York, NY 10014.
*In accordance with the Iowa Board of Nursing Administrative rules governing
grievances, a copy of your evaluation of the CE offering (section C) may be sub-
mitted directly to the Iowa Board of Nursing.
CE TEST: Genes and Inheritance
Lindsay A. Middelton, RN, CGC; Kathryn F. Peters, MS
General Purpose: To present registered professional nurses with an
overview of basic genetic concepts, including inheritance patterns, pedi-
gree constructions, chromosome aberrations, and the multifactorial basis
underlying the common diseases of adulthood.
Objectives: After reading this article and taking this test, you will be able
to:
1. Outline factors helpful in understanding, identifying, and distinguishing
autosomal recessive, autosomal dominant, and X-linked genetic disor-
ders.
2. Describe the symbols and notations used to construct a genetic pedi-
gree.
3. Explain features of chromosomal and other genetic disorders.
CE Test
1. A child of parents who are both carriers of
an autosomal recessive genetic disorder has a
50% chance of
2. An example of an autosomal recessive dis-
order is
a. neurofibromatosis.
b. xeroderma pigmentosum.
c. von Hippel-Landau syndrome.
d. nonpolyposis colorectal cancer.
3. A child of a person who has an autosomal
dominant condition
a. can only get the condition if both parents have it.
b. has a 25% chance of getting the condition.
c. can only get the condition if he is male.
d. has a 50% chance of getting the condition.
a. having the disorder.
b. not having the disorder and not being a carrier.
c. not having the disorder and being a carrier.
d. having the disorder, but only if he is male.
CONTINUING EDUCATION ENROLLMENT FORM: GENES AND INHERITANCE
A
Credit: 3.0 contact hours Fee: $19.95 Registration deadline: October 31, 2003
Directions: Complete sections A, B, and C of this form and return it to:
Lippincott Williams & Wilkins, Inc., CE Department, 345 Hudson Street, NY, NY 10014
Important: Please complete information:
Issue Date: _________________________________
Last Name ____________________________________________________ First Name __________________________________________________ MI_______
Address _________________________________________________________ City __________________________________ State ________Zip____________
Telephone # ______________________________________ SS# ________________________________________
State of Licensure #1 ________________ License No. #1 ______________________________________
State of Licensure #2 ________________ License No. #2 ______________________________________
Title _______________________________________________________________
RN
RN
LPN
LPN
Other
Other
❍
❍
❍
❍
❍
❍
Clinical Specialty — Where You Work Most Often ______________________________
C
B
Test Responses: Darken one for your answer to each question.
1. Did this CE activity’s learning objectives relate to its general
purpose? ___ Y ___ N
A
B
C
D
A
B
C
D
A
B
C
D
2. Was the journal home study format an effective way to present the
material?___ Y ___ N
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
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❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
❍ ❍ ❍ ❍
3. Was the content current to nursing practice? ___ Y ___ N
4. How long did it take you to complete this CE activity? _______ hours
5. Suggestions for future topics _____________________
_____________________________________________
Genes and Inheritance
Cancer Nursing™, Vol. 24, No. 5, 2001 ꢀ 369

4. An example of an autosomal dominant dis- 9. The designation 17p refers to
14. The function of a codon is to specify the
production of a single
a. protein.
b. DNA strand.
c. amino acid.
order is
a. the long arm of autosome 17.
a. tuberous sclerosis.
b. Wiskott-Aldrich syndrome.
c. Fancomi anemia.
d. Bloom syndrome.
b. the short arm of autosome 17.
c. the long arm of sex chromosome 17.
d. the short arm of sex chromosome 17.
d. chromosome.
15. One nitrogenous base substituted for
another creates an error called a
a. point mutation.
b. splice-site mutation.
c. frameshift mutation.
5. A man who has an X-linked condition will
pass the
a. condition to all of his daughters.
b. carrier state to all of his daughters.
c. condition to all of his sons.
d. carrier state to all of his sons.
10. Down syndrome is an example of
a. having an extra chromosome.
b. structurally rearranged chromosomes.
c. having a missing chromosome.
d. multifactorial inheritance.
d. silent mutation.
16. When all the codons following the insertion
or deletion of single or multiple bases are
affected, the mutation is called a
a. point mutation.
b. splice-site mutation.
c. frameshift mutation.
6. In a family history constructed in a pedi- 11. The way a person’s inherited characteris-
gree format, a shaded circle connected by a tics are demonstrated in features like height
horizontal line to an unshaded square indi- and hair color is called that person’s
cates
a. genotype.
a. a married couple in which the wife has b. genome.
the indicated disorder and the husband does c. phenotype.
d. silent mutation.
not.
d. phenome.
b. a mother whose son has the indicated disorder.
c. a married couple in which the husband is
deceased and the wife is alive.
d. a father whose daughter has the indicated dis-
order.
17. Linkage analysis
a. is a direct process that identifies a precise gene
mutation.
12. Low penetrance of a genetic disorder
means that
a. a person is unlikely to inherit the gene for the b. is rarely used in the research setting.
disorder. c. usually involves testing a single family member.
b. a person who has the gene that causes a d. tracks known sequences of DNA near the gene
7. In a family history constructed in a pedigree
format, a diagonal line through a circle indi-
cates
particular condition might not have the clin-
ical features of the condition.
of interest from generation to generation.
a. unknown paternity.
b. a deceased female.
c. a male with the indicated condition.
d. an unmarried female.
c. clinically affected people in a family may
have variations in the severity of the dis-
ease.
d. the genetic disorder cannot be passed to
subsequent generations.
8. In a family history constructed in a pedigree
format, a symbol with the number 2 inside it
indicates
a. a married couple.
b. two people who have the indicated condition.
13. The nitrogenous base guanine is always
paired with which of the following nitrogenous
bases?
c. two individuals of the same gender, whether a. adenine
male, female, or unknown. b. thymine
d. the second generation represented in the c. guanine
pedigree. d. cytosine
370 ꢀ Cancer Nursing™, Vol. 24, No. 5, 2001
Middelton & Peters