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ESSENTIALS OF PATHOPHYSIOLOGY
CHAPTER 6
GENETIC AND CONGENITAL
DISORDERS
PRE LECTURE QUIZ (TRUE/FALSE)
T

F

F

T

F

Most genetic disorders are caused by an alteration in
the deoxyribonucleic acid (DNA) sequence that alters
the synthesis of a single gene product.
Autosomal recessive disorders are manifested even if
only one member of the gene pair is affected.
A teratogenic agent is an environmental agent that
produces abnormalities only during the first 4 weeks
of embryonic or fetal development.
Down syndrome, Turner syndrome, and Klinefelter
syndrome are all examples of chromosomal disorders
that occur from an alteration in chromosome number.
Cleft lip and palate is an example of an autosomal
dominant disorder.
PRE LECTURE QUIZ

Autosomal dominant disorders involve a
______________ mutant allele that is transmitted
from an affected parent to an offspring.
Single

Sex-linked disorders almost always are associated
with the __________ chromosome and are
predominantly recessive.
Folic

An individual with ______________ syndrome would
be female, short in stature, and lacking in breast
development, and would not menstruate.
Turner

_____________________, an autosomal dominant
disorder, is a condition involving neurogenic tumors
that arise from Schwann cells and other elements
of the peripheral nervous system.
Neural tube defects are often the result of
______________ acid deficiency.
Neurofibromatosis
X

GENES ARE FOUND ON CHROMOSOMES


X or Y chromosome: sex-linked
Other chromosomes: autosomal
Tree Structure
Female Male
Without Trait
With Trait
Autosomal Recessive Trait Carriers, Diseased and non Diseased
Sex Linked showing Female Carriers
ALLELES

Alleles are copies of a gene

If all your copies of a gene are alike, you are
homozygous

If they differ, you’re heterozygous


If you are heterozygous for a recessive trait and do
not show it, you are a carrier
If you have only one copy of a gene, you are
hemizygous
QUESTION
Which of the following statements is true about
an individual who is a carrier for the cystic
fibrosis (CF) gene?
a. Homozygous; suffers from CF
b. Homozygous; does not suffer from CF
c. Heterozygous; suffers from CF
d. Heterozygous; does not suffer from CF
ANSWER
Heterozygous; does not suffer from CF
If an individual is a carrier, they are heterozygous
for the recessive trait (in this case, CF), but
they do not display the trait (because the trait
is recessive).
d.
DISCUSSION:
If you have the allele for a trait, do you display
the trait?

No: It is recessive

Yes: It is dominant

Sometimes: It has intermediate
penetrance
SCENARIO:
A Young Man’s Father Died of Brugada Syndrome …
 Unexplained sudden death
 Due to mutation in the gene from the Na+ channel in
cardiac muscle
 Autosomal dominant trait
 His mother is alive and healthy
 Both grandmothers are alive and healthy
Question:
What is the son’s chance of having the disease?
PUNNETT SQUARE: SINGLE-GENE AUTOSOMAL
Mom’s
alleles
b
b
b
bb
bb
B
Bb
Bb
Dad’s
alleles
PENETRANCE
Brugada syndrome has only a 12.5%
penetrance
 What does this mean for the young man
whose father died of it?

SEX-LINKED TRAITS

The gene is usually on the X chromosome

If Brugada syndrome were sex-linked, what would the
young man’s father’s genotype have been?

What would his chances of inheriting the disease be?
QUESTION
If an unaffected mother carries one normal and
one mutant allele on her X chromosome, what
are the chances that she will transmit the
defective gene to her sons?
a. 25%
b. 50%
c. 75%
d. 100%
ANSWER
50%
Because a son receives the X sex chromosome
from his mother (who has one normal and one
mutant allele), there is a 50% chance that the
mutant allele will be inherited.
b.
PUNNETT SQUARE: SINGLE-GENE SEX-LINKED
Mom’s
alleles
Xb
Xb
Y
Xb Y
Xb Y
XB
Xb XB
Xb XB
Dad’s
alleles
MITOCHONDRIAL DNA

Codes for the proteins needed for aerobic metabolism
Mitochondria all come from the mother
 She has many more than two mitochondria,
so she may pass several different mitochondrial alleles to
the child

(Mendelian Inheritance in Man. [2005]. Mitochondrial deafness modifier gene.
Retrieved May 15, 2005, from http://www.ncbi.nlm.nih.gov/entrez/
dispomim.cgi?cmd=entry&id=221745.)
CHROMOSOMAL DAMAGE

Breakage and
rearrangement
 Deletion
 Inversion
 Isochromosome
formation
 Ring formation
 Translocation
QUESTION
Which type of chromosome alteration generally
results in normal offspring?
a.
b.
c.
d.
Deletion
Inversion
Translocation
Ring formation
ANSWER
Translocation
Translocation is the only chromosomal alteration
where no genetic material is actually lost
(chromosome parts are exchanged), so the
offspring are usually normal. Offspring are
translocation carriers, so their children may or
may not be normal.
c.
ALTERATIONS IN CHROMOSOME DUPLICATION


Mosaicism
Aneuploidy
 Monosomy
 Polysomy
 Trisomy
º Down syndrome
Klinefelter’s Syndrome
ENVIRONMENTAL CAUSES FOR CONGENITAL
DISORDERS
Scenario:
Mrs. K is a diabetic and is having trouble keeping
her blood glucose constant during pregnancy…
 She works in a dry-cleaners store next to a gas
station and drinks heavily.
 She is diagnosed with toxoplasmosis.
Question:
What kinds of stresses is her fetus experiencing?