NU545 Physio-Pathological Basis of Advanced Nursing Study Guide
Chapters 4–6, 12–14, & 46–49 McCance and Huether 7th edition
SECTION I: STUDY GUIDE
1. Describe the specific chromosomal abnormality responsible for Down
syndrome (pp. 145-147; key search term: “example of aneuploidy”)
Aneuploid cells are defined as those that do not contain a multiple of 23
chromosomes. An aneuploid cell containing 3 copies of one chromosome is
said to be trismic (condition called trisomy). Newborns with trisomy of
chromosomes 13, 18, or 21 can survive. The most well- known example of
aneuploidy in an autosome is trisomy of the 21st chromosome, which causes
Down syndrome. One of the most common is trisomy X. About ¾ of infants
born with Down syndrome die during their first 10 years of life. For those that
survive, life expectancy is 60 years.
Aneuploidy is usually the result of nondisjunction, an error in which
homologous chromosomes or sister chromatids fail to separate normally during
meiosis or mitosis. 97% of Down syndrome cases are caused by nondisjunction
during the formation of one of the parents’ gametes or during early embryonic
development, and the remaining 3% by translocations. In 95%, the
nondisjunction occurs in the formation of the mother’s egg cell.
About 1% have mosaics in which large numbers of normal cells are present,
causing less effects of trismic cells and are attenuated.
The risk of having a child with Down syndrome increases with maternal age.
2. Causes of mental retardation. (pp. 143-151; key search term:
“major chromosome”)
Chromosome abnormalities are the leading known cause of mental retardation
and miscarriage. A major chromosome aberration occurs in more than half of
conception. Most of these fetuses do not survive to term; about 50% of all
recovered first-trimester spontaneous abortions have major chromosomal
aberrations. Approximately 1 in 150 live births has a major diagnosable
chromosomal abnormality.
2
,Examples: Aneuploidy (cells that do not contain a multiple of 32 chromosomes;
i.e., Down syndrome, Turner Syndrome, Klinefelter syndrome). Chromosome
breakage – deletions: broken chromosomes and loss of DNA; usually a gamete
with a deletion unite with a normal gamete to form a zygote, thus one zygote has
one chromosome with a normal complement of genes and one with some missing
genes (cri du chat syndrome or “cry of the cat” or cry of the affected child).
Translocations: interchanging of genetic material between nonhomologous
chromosomes (Robertsonian translocation) Fragile sites: A number of areas on
chromosomes
3
,develop microscopically observable breaks and gaps when the cells are cultured.
Example: fragile X syndrome, which is associated with substantial cognitive
impairment (second most common genetic cause of mental retardation after
Down syndrome).
Examples include:
Polyploidy (which is when a euploid cell has more than the diploid number of
chromosomes
—includes triploid which is 3 copies of each chromosome and tetraploid—4 copies)
and
Aneuploidy (do not contain a multiple of 23 chromosomes—includes
monosomy which is the presence of only one copy of a given chromosome, and
trisomy which is 3 copies of one chromosome).
Examples of chromosome abnormalities that lead to mental retardation are: Down
syndrome (1st most common cause), trisomy X 3 or more chromosomes, cri du
chat syndrome, fragile X syndrome (2nd most common cause), Klinefelter
syndrome, untreated phenylketonuria (PKU), Wilms tumor, Angelman syndrome,
and 75% of people with spina bifida.
3. What gene abnormality causes cystic fibrosis? (pp. 154-155, 1310;
key search term: “common lethal recessive”)
CF is an autosomal recessive inherited disease characterized by delayed age of
onset, incomplete penetrance, and variable expressivity.
The CF gene, cystic fibrosis transmembrane conductance regulator gene
(CFTCR), is located on the long arm of chromosome 7 which encodes the protein
transmembrane conductance regulator that functions as a chloride channel and
is regulated by cyclic adenosine monophosphate (cAMP) in the membranes of
specialized epithelial cells. Mutation results in abnormal expression of CFTCR and
is associated with defective epithelial chloride ion transport which leads to a salt
imbalance that results in secretions of abnormally thick, dehydrated mucus.
There are more than 1900 known mutations of this gene divided into 6 classes
with varying severity of disease expression.
It is the most common lethal autosomal recessive disease in white children and
approximately 1 in 25 whites carries one copy of an allele that can cause CF.
4. How is a recessive disease inherited? (pp. 151, 154-156; key search term:
“hiding in carriers”)
Most recessive disease-causing alleles occur in heterozygotes (genes are not
identical at the locus – the position along a chromosome that each gene occupies)
4
, who carry one copy of the allele but do not express the disease. Because many
recessive genes are lethal in the homozygous (genes are identical at the locus)
state, they are eliminated from the population when they occur in homozygotes.
By “hiding” in carriers, however, most recessive genes for diseases survive to be
passed on to the next generation. The number of carriers for recessive diseases
can be high, but recessive diseases are rare. The most common lethal recessive
disease in white children is cystic fibrosis. Because an individual must be
homozygous for a recessive allele to express the disease, the carriers are
phenotypically normal. Because most recessive alleles are maintained in normal
carriers, they are able to survive in the population from one generation to the
next. As with many autosomal dominant diseases, many autosomal recessive
diseases are characterized by delayed age of onset, incomplete penetrance, and
variable expressivity.
Important criteria for discerning autosomal recessive inheritance include the
following:
1. Males and females are affected in equal proportions.
2. Consanguinity (marriage between related individuals) is often present.
3. The disease is seen in siblings but usually not in their parents.
4. On the average, ¼ of the offspring of carrier parents will be affected.
In most cases of recessive disease, both parents of affected individuals are
heterozygous carriers. On the average, one fourth of their offspring will be
normal
5
Chapters 4–6, 12–14, & 46–49 McCance and Huether 7th edition
SECTION I: STUDY GUIDE
1. Describe the specific chromosomal abnormality responsible for Down
syndrome (pp. 145-147; key search term: “example of aneuploidy”)
Aneuploid cells are defined as those that do not contain a multiple of 23
chromosomes. An aneuploid cell containing 3 copies of one chromosome is
said to be trismic (condition called trisomy). Newborns with trisomy of
chromosomes 13, 18, or 21 can survive. The most well- known example of
aneuploidy in an autosome is trisomy of the 21st chromosome, which causes
Down syndrome. One of the most common is trisomy X. About ¾ of infants
born with Down syndrome die during their first 10 years of life. For those that
survive, life expectancy is 60 years.
Aneuploidy is usually the result of nondisjunction, an error in which
homologous chromosomes or sister chromatids fail to separate normally during
meiosis or mitosis. 97% of Down syndrome cases are caused by nondisjunction
during the formation of one of the parents’ gametes or during early embryonic
development, and the remaining 3% by translocations. In 95%, the
nondisjunction occurs in the formation of the mother’s egg cell.
About 1% have mosaics in which large numbers of normal cells are present,
causing less effects of trismic cells and are attenuated.
The risk of having a child with Down syndrome increases with maternal age.
2. Causes of mental retardation. (pp. 143-151; key search term:
“major chromosome”)
Chromosome abnormalities are the leading known cause of mental retardation
and miscarriage. A major chromosome aberration occurs in more than half of
conception. Most of these fetuses do not survive to term; about 50% of all
recovered first-trimester spontaneous abortions have major chromosomal
aberrations. Approximately 1 in 150 live births has a major diagnosable
chromosomal abnormality.
2
,Examples: Aneuploidy (cells that do not contain a multiple of 32 chromosomes;
i.e., Down syndrome, Turner Syndrome, Klinefelter syndrome). Chromosome
breakage – deletions: broken chromosomes and loss of DNA; usually a gamete
with a deletion unite with a normal gamete to form a zygote, thus one zygote has
one chromosome with a normal complement of genes and one with some missing
genes (cri du chat syndrome or “cry of the cat” or cry of the affected child).
Translocations: interchanging of genetic material between nonhomologous
chromosomes (Robertsonian translocation) Fragile sites: A number of areas on
chromosomes
3
,develop microscopically observable breaks and gaps when the cells are cultured.
Example: fragile X syndrome, which is associated with substantial cognitive
impairment (second most common genetic cause of mental retardation after
Down syndrome).
Examples include:
Polyploidy (which is when a euploid cell has more than the diploid number of
chromosomes
—includes triploid which is 3 copies of each chromosome and tetraploid—4 copies)
and
Aneuploidy (do not contain a multiple of 23 chromosomes—includes
monosomy which is the presence of only one copy of a given chromosome, and
trisomy which is 3 copies of one chromosome).
Examples of chromosome abnormalities that lead to mental retardation are: Down
syndrome (1st most common cause), trisomy X 3 or more chromosomes, cri du
chat syndrome, fragile X syndrome (2nd most common cause), Klinefelter
syndrome, untreated phenylketonuria (PKU), Wilms tumor, Angelman syndrome,
and 75% of people with spina bifida.
3. What gene abnormality causes cystic fibrosis? (pp. 154-155, 1310;
key search term: “common lethal recessive”)
CF is an autosomal recessive inherited disease characterized by delayed age of
onset, incomplete penetrance, and variable expressivity.
The CF gene, cystic fibrosis transmembrane conductance regulator gene
(CFTCR), is located on the long arm of chromosome 7 which encodes the protein
transmembrane conductance regulator that functions as a chloride channel and
is regulated by cyclic adenosine monophosphate (cAMP) in the membranes of
specialized epithelial cells. Mutation results in abnormal expression of CFTCR and
is associated with defective epithelial chloride ion transport which leads to a salt
imbalance that results in secretions of abnormally thick, dehydrated mucus.
There are more than 1900 known mutations of this gene divided into 6 classes
with varying severity of disease expression.
It is the most common lethal autosomal recessive disease in white children and
approximately 1 in 25 whites carries one copy of an allele that can cause CF.
4. How is a recessive disease inherited? (pp. 151, 154-156; key search term:
“hiding in carriers”)
Most recessive disease-causing alleles occur in heterozygotes (genes are not
identical at the locus – the position along a chromosome that each gene occupies)
4
, who carry one copy of the allele but do not express the disease. Because many
recessive genes are lethal in the homozygous (genes are identical at the locus)
state, they are eliminated from the population when they occur in homozygotes.
By “hiding” in carriers, however, most recessive genes for diseases survive to be
passed on to the next generation. The number of carriers for recessive diseases
can be high, but recessive diseases are rare. The most common lethal recessive
disease in white children is cystic fibrosis. Because an individual must be
homozygous for a recessive allele to express the disease, the carriers are
phenotypically normal. Because most recessive alleles are maintained in normal
carriers, they are able to survive in the population from one generation to the
next. As with many autosomal dominant diseases, many autosomal recessive
diseases are characterized by delayed age of onset, incomplete penetrance, and
variable expressivity.
Important criteria for discerning autosomal recessive inheritance include the
following:
1. Males and females are affected in equal proportions.
2. Consanguinity (marriage between related individuals) is often present.
3. The disease is seen in siblings but usually not in their parents.
4. On the average, ¼ of the offspring of carrier parents will be affected.
In most cases of recessive disease, both parents of affected individuals are
heterozygous carriers. On the average, one fourth of their offspring will be
normal
5
