Download Patterns of Autosomal Inheritance

S E C T I O N
7.1
Patterns of Autosomal Inheritance
E X P E C TAT I O N S
Understand the difference
between genetic conditions
and genetic disorders.
Describe genetic disorders
involving autosomal and
sex-linked inheritance.
Perform laboratory simulations
to explore heterozygous
advantage.
Figure 7.1 Albinism is a rare
condition among many
organisms. It results from
a lack of melanin, a normal
skin pigment.
In 1649, an English boy visited his physician,
complaining that he was producing black urine.
The physician concluded that a fire in the boy’s
belly was charring and blackening his bile, and that
the resulting ashes were then passing into his
urine. The physician treated the patient with
bleedings, cold baths, a diet of cold liquids, and
various drugs. Eventually, the boy grew tired of the
therapy (which had no effect) and decided to let
nature take its course. He grew into manhood,
married, had many children, and lived a long,
healthy life — always passing urine as black as ink.
We now know that the boy was suffering from a
hereditary condition called alkaptonuria. In most
individuals, an enzyme converts the inky black
urine to its usual colour. In individuals with the
condition, the genes that code for the production
of this enzyme are not functioning. Enzymes are
proteins manufactured from specific instructions
carried by specific genes. As you have learned in
Chapter 6, genes indicate the exact sequence of
amino acids required to make a given protein. The
wrong instructions are given when an allele is
mutated. This results in an inappropriate sequence
of amino acids and creates a defective protein.
BIO
FACT
Using special biochemical techniques, scientists discovered
the disease alkaptonuria in an Egyptian mummy more than
3500 years old.
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PAUSE
RECORD
Enzymes are important chemical catalysts in the body.
How do catalysts affect chemical reactions? Are catalysts
changed in any way during these reactions? Write your
answers in your notebook.
There are many genetic conditions within the
human population. For example, albinism (as
shown in Figure 7.1) is a rare genetic condition,
but it is not life-threatening. Other genetic
disorders, however, can cause severe medical
problems. Why would harmful alleles that cause
disease and early death continue to exist in our
population? Recall what you have learned about
dominant and recessive alleles and the concept of
carriers. In heterozygotes, a normal dominant allele
may mask the effects of a harmful recessive one.
Thus, the parent is not affected but can pass on the
harmful allele to offspring. Also, mutations
constantly create new alleles, both harmful and
harmless, within a population. Introduction of new
alleles creates variation within the population.
Variation allows individuals to better adapt to
environmental change.
Family pedigrees show us that some traits are
inherited according to the principles that Mendel
described. Traits can be carried by dominant or
recessive alleles, and genes themselves are carried
on chromosomes. As you have learned, some genes
are carried only on a sex chromosome (usually the
X chromosome) and are called sex-linked traits.
Many others are carried on autosomes, which are
any of the remaining 22 pairs of chromosomes that
make up the human genome. Other genetic traits in
the human population are not due to dominant or
recessive alleles. Instead, they arise when there are
changes in the number of chromosomes or in the
actual structure of chromosomes.
Autosomal Recessive Inheritance
There are many autosomal recessive disorders.
Such disorders are carried on the autosomes and
are not specific to the sex of the person. One
example of such a disorder is Tay-Sachs disease.
Children with Tay-Sachs disease appear normal at
birth; however, their brains and spinal cords begin
to deteriorate at about eight months of age. By their
first birthday, these children are blind, mentally
handicapped, and display little muscular activity.
Most die before their fifth birthday.
Individuals with Tay-Sachs disease lack an
enzyme in the lysosomes of their brain cells.
Lysosomes are cell organelles in which large
molecules are digested. The recessive allele does
not code for the production of the enzyme
responsible for breaking down specific lipids inside
the lysosomes. As undigested lipids build up
inside the affected person, the lysosomes become
enlarged and eventually destroy the brain cells that
house them (see Figure 7.2).
Figure 7.2 Electron micrograph of brain tissue of a person
affected with Tay-Sachs disease shows enlarged lysosomes
filled with lipid deposits. An enzyme deficiency prevents
these deposits from being degraded.
There is no treatment for Tay-Sachs disease.
However, a blood test has been developed to
identify heterozygous carriers. Carriers have half
the enzyme levels of normal individuals, which is
enough to function normally. Before the
development of this test, the incidence of TaySachs disease was particularly high among
Ashkenazic Jews. The origins of Ashkenazic Jews
lie in Central and Eastern Europe and today they
comprise 90% of the North American Jewish
population. It is believed that the long isolation of
these people in small European communities led to
the increased frequency of the recessive allele
within their population. Although Tay-Sachs
disease has always been rare in the general North
American population (one in 300 000 births), it
was far more common among Ashkenazic Jews and
their descendants (one in 3600 births). Since the
availability of the blood test for carriers, the
incidence of Tay-Sachs disease within this Jewish
population has dropped dramatically.
Math
LINK
You can use simple Mendelian genetics to determine if a
condition or disorder is due to an autosomal recessive allele. If
both parents are heterozygous carriers of a recessive allele,
what proportion of their children will be at risk of inheriting
both copies of the allele? What proportion will be at risk if both
parents are affected, meaning that they are both homozygous
recessive? Construct Punnett squares and present your
findings as genotype and phenotype ratios. See Chapter 4,
Section 4.2 to review how Punnett squares are constructed.
Another autosomal recessive disorder that affects
young children is phenylketonuria (PKU). In
individuals with this condition, an enzyme that
converts phenylalanine to tyrosine is either absent
or defective. Phenylalanine is an amino acid
essential for regular growth and development, and
for protein metabolism. Tyrosine, another amino
acid, is used by the body to make melanin and
certain hormones. The phenylalanine in children
with PKU is broken down abnormally. In ways that
we do not yet understand, the products of this
process damage the developing nervous system.
Babies with phenylketonuria appear normal at
birth. If their condition is not diagnosed and
treated, however, they will become severely
mentally handicapped within a few months.
Fortunately, newborns today are routinely tested
for PKU. Infants who test positive for the disorder
are placed on a special diet that prevents the
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harmful products from accumulating. Once their
nervous systems are fully developed, these
individuals can go on to lead healthy lives.
Albinism is a genetic condition in which the
eyes, skin, and hair have no pigment. The colour of
our hair, skin, and eyes is due to varying amounts
of a brown pigment called melanin, which is
produced in special pigment cells. People who are
homozygous for this autosomal recessive allele
either lack one of the enzymes required to produce
melanin or, if the enzyme is present, lack the
means to get the enzyme to enter the pigment cells.
Codominant Inheritance
Sickle cell anemia is one of the better-known
examples a codominant genetic disorder. Affected
individuals have a defect in the hemoglobin in red
blood cells. This defect leads to blood clots and
reduced blood flow to vital organs. As a result, they
have little energy, suffer from various illnesses, and
are in constant pain. Many die prematurely.
Hemoglobin is a complex protein that is
synthesized and transported in red blood cells.
This unique molecule has the ability to pick up
oxygen from the lungs, transport it to the tissues,
and release it to the body’s cells. Like all proteins,
hemoglobin is made up of a sequence of amino
acids. The sequence in hemoglobin consists of four
separate polypeptide chains (two identical alpha
chains and two identical beta chains) of about 150
amino acids each, as shown in Figure 7.3. When
individuals inherit the allele for sickle cell anemia,
one amino acid (glutamic acid) at a specific
location in the beta chain is replaced by another
(valine), resulting in abnormal hemoglobin.
Figure 7.4 shows the inheritance pattern for sickle
cell anemia. The allele HbS indicates the abnormal
hemoglobin in sickle cell anemia and the allele
HbA indicates normal hemoglobin.
The abnormal hemoglobin can pick up oxygen at
the lungs and transport it to body tissues just as
normal hemoglobin does. The oxygen diffuses from
the blood across the capillary walls and into the
tissue spaces. When the oxygen is released, however,
the abnormal hemoglobin changes shape and
begins to clump with other hemoglobin molecules
in the red blood cell. The red blood cell becomes
stiff and deformed, frequently forming a crescent or
sickle shape (see Figure 7.5). These deformed cells
block capillaries in the joints and vital organs. The
condition becomes life-threatening when vessels to
vital organs are blocked, because the blockage
prevents other red blood cells from reaching these
organs with a fresh supply of oxygen. The sickle
cells are also very fragile and break down quickly.
This results in a condition called anemia, where
the overall red blood cell count is too low to
support the body’s oxygen requirements.
capillary
iron
heme
group
alpha
chain
beta
chain
molecule
has helical
shape
beta
chain
alpha
chain
Red blood cells inside a capillary
Red blood cell
Figure 7.3 Red blood cells, shown moving through a
capillary in the photograph at left, contain many molecules
of hemoglobin like the one pictured at right. Each molecule
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Hemoglobin molecule
of hemoglobin is composed of two alpha and two beta
chains of amino acids.
sickle-cell
trait
sickle-cell
trait
HbAHbS
HbAHbS
HbAHbA
HbAHbS
normal
sickle-cell
trait
HbAHbS
HbSHbS
sickle-cell
trait
sickle-cell
disease
Figure 7.4 Inheritance of sickle cell anemia. In this example, each parent is
heterozygous for the sickle cell trait. Among the offspring, there is a 50% chance of
inheriting the sickle cell trait, a 25% chance of having sickle cell anemia, and a 25%
chance of not having the disease.
Magnification: 90 000 x
Magnification: 90 000 x
Red blood cells containing normal hemoglobin are round and
smooth, allowing them to pass through capillaries easily.
Sickled red blood cells have elongated, blunt shapes that
stick easily in capillaries and clog them.
Figure 7.5 Electron micrographs of normal and sickled red blood cells.
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Heterozygous Advantage
The recessive allele that causes sickle cell anemia
is thought to have originated in Africa. Until
recently, homozygous recessive individuals never
survived to become parents, indicating that the
recessive allele was constantly being removed from
the population. Yet in some African regions, almost
half the population is heterozygous for sickle cell
anemia. Geneticists wondered how this allele could
remain at such high levels when it was constantly
being removed from the population.
The answer came from studying another serious
disease in the regions where sickle cell anemia is
most commonly found. In Africa, malaria is a
leading cause of illness and death, particularly
among the young. Studies revealed that children
who were heterozygous for sickle cell anemia were
less likely to contract malaria and therefore more
likely to survive to parenthood. For reasons yet
unknown, heterozygous females are also more
fertile than homozygous females.
Wo rd
LINK
The word “malaria” comes from the Italian words mala aria,
meaning bad air, because it was once thought that the disease
was caused by inhaling the air around stagnant waters or by
drinking from them.
BIO
FACT
The association of malaria with stagnant water is at least
partly correct, since malaria is caused by an infection of red
blood cells by protozoa of the genus Plasmodium. These
protozoa are carried to their hosts by female mosquitoes of
the Anopheles genus. Like other mosquitoes, they lay their
eggs in slow-moving or stagnant water.
The inheritance of one allele for sickle cell
anemia is a classic example of heterozygous
advantage, in which individuals with two different
alleles for the same trait have a better rate of
survival. Homozygous dominant individuals do not
inherit the allele for sickle cell anemia. However,
their normal-shaped red blood cells provide a
perfect home for the protozoa that cause malaria.
These homozygous dominant individuals are easily
infected and, if born in malarial regions, often do
not live to reproductive age. Homozygous recessive
individuals with sickled cells may not contract
malaria, but are likely to die young from the
numerous symptoms of sickle cell anemia. In
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comparison, heterozygous individuals produce
enough normal red blood cells to meet their bodies’
oxygen demands and enough sickled cells to
reduce their susceptibility to malaria. Clearly, in
this case it is an advantage to be a heterozygous
carrier of the sickle cell allele.
In 1949, two biochemists, Linus Pauling and
Harvey Itano, performed gel electrophoresis on
both HbS and HbA hemoglobin molecules. Gel
electrophoresis is a procedure in which molecules
are placed on a viscous gel that is sandwiched
between glass or plastic plates. The procedure is
outlined in Figure 7.6.
Pauling and Itano discovered that HbS and HbA
migrated independently of one another and formed
two distinct bands on the gel. They knew that the
molecule that had the greatest negative charge
would migrate faster and farther. This proved to be
the normal HbA molecule. Can you explain why?
Other scientists later explained that the HbS
molecule travelled more slowly because it
contained the neutral amino acid valine at a site
where the more negative amino acid glutamic acid
was found in the HbA molecule. Therefore, the
more negative HbA molecule migrated faster across
the gel toward the positively charged end,
separating itself from the HbS molecule. This work
paved the way for an important discovery in the
field of genetics: the conclusion that genes code for
the production of all proteins, not just enzymes. In
the next investigation, you will model the
inheritance of a recessive allele and heterozygous
advantage in a population.
PLAY
To explore gel electrophoresis and DNA testing, refer to
your Electronic Learning Partner.
Autosomal Dominant Inheritance
Researchers can use two pieces of evidence from
Mendelian genetics to determine if an autosomal
dominant allele is responsible for a trait. First,
since a dominant allele is expressed in
heterozygotes as well as in homozygous dominant
individuals, the trait will appear in every
generation. Second, if one parent is heterozygous
and the other is homozygous recessive for the
allele, then 50% of the offspring will have the trait.
A Restriction enzymes Either one or
several restriction enzymes are added
to a sample of DNA. The enzymes cut
the DNA into fragments.
B The gel A gel, with a consistency similar
to gelatin, is formed so small wells are left
at one end. Small amounts of the DNA
sample are placed into these wells.
gel
DNA fragments
negative end
power
source
E Before the DNA fragments are added to
the wells, they are treated with a dye that
glows under ultraviolet light, allowing the
bands to be studied.
positive end
C The electrical field The gel is placed in a
solution, and an electrical field is set up
so one end of the gel is positive and the
other end is negative.
longer
fragments
shorter
fragments
completed gel
D The fragments move The
negatively charged DNA fragments
travel toward the positive end. The
smaller the fragment, the faster it
moves through the gel. Fragments
that are the farthest from the well
are the smallest.
Figure 7.6 Gel electrophoresis
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Investigation
SKILL FOCUS
7 • A
Predicting
Genes and Populations
Performing and recording
You have learned how certain autosomal recessive traits may affect
humans. Such traits are inherited from parents who carry the recessive
condition. Other organisms, too, carry recessive traits that may be
passed on to offspring. In this investigation, your class will model the
inheritance of alleles in a population of randomly mating American
coots. The American coot is a large, duck-like bird with a very short,
thick, red-tipped bill. It breeds throughout much of southern Canada
and is a common summer resident of Lakes Erie and Ontario.
Approximately 50% of the starting coots will be heterozygous (Aa),
25% will be dominant (AA) and 25% will be recessive (aa). As a
participant, your job will be to record the genotypes of your offspring,
compare them with those of others, and interpret the results.
Modelling concepts
Analyzing and interpreting
Materials
2 equal stacks of large index cards (the stock supply),
each marked “A” or “a” on one side only
notebook
pencil
eraser
Procedure
1. You will be given your initial genotype on
two cards, one with each allele of your
genotype. In your notebook, make a chart
similar to the one shown here. Record the
initial percentages of each genotype and
your initial genotype on it.
Data Chart
Initial percentages
American coot
My initial genotype
Pre-lab Questions
F1
What will happen to the coot population if the
recessive allele codes for a serious genetic
disorder?
What will happen to the coot population if the
recessive allele also confers partial immunity
against some other serious disorder?
Problem
How will you decide which coot genotype is
best equipped to survive?
Prediction
Predict the percentage of the total population
that each genotype will represent after five
generations (steps 1–6 and 7) and 10 generations
(step 8).
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AA
Aa
aa
AA
Aa
aa
F2
F3
F4
F5
Final percentages
2. Place your two allele cards behind your
back and shuffle them. Once mating season
begins you may confidently approach
another student with that classic line, “Coot,
coot?” to which your “mate” will reply,
“Coot, coot!” You and your “mate” will then
simultaneously present one of your cards to
each other. These two cards become the
genotype of your first offspring, while the
remaining two cards become the genotype of
your second offspring.
3. If the genotype of either offspring is “aa,” it
will die. Keep trying until you produce two
surviving offspring (see Rules of the Game).
4. Now assume that your parent genotypes die
and that you and your mate assume the
genotypes of your offspring. You may need
to get new cards from the stock supply to do
this. Record your new genotype as the
F1 generation on the chart.
5. Thank your partner, locate a new “mate,”
and repeat steps 2 through 4, recording the
genotypes of the new offspring as the
F2 generation. Repeat this procedure until
you have completed all five generations.
6. Pool the class data, tally the number of
students with each genotype, and calculate
and record the final percentage of AA, Aa,
and aa genotypes.
7. Now begin again with your original
genotype and repeat steps 1 through 6 while
filling in a second chart. If any offspring is
“AA,” however, you must flip a coin. If it
lands “heads,” the offspring lives. If it lands
“tails,” it dies. Parents must continue to
“mate” until two viable offspring are created
for each generation.
8. Tally the class data after five generations,
then proceed through another five
generations using a third chart and tally the
data again.
Post-lab Questions
1. According to the first chart tally, what
happened to the population after five
generations?
2. Which genotype did “nature” work to select
against?
3. Would it be possible to completely eliminate
this genotype from this population?
4. What changed in steps 7 and 8?
5. What happened to the population according
to the second and third chart tallies in steps
7 and 8? Compare these results to those of
the first chart tally.
6. Can the recessive allele be completely
eliminated in steps 7 and 8?
Conclude and Apply
7. Discuss the role of heterozygous advantage
in maintaining genetic variation.
8. How can you relate the results you have
observed to the pattern of sickle cell anemia
inheritance in human populations?
Exploring Further
9. Evidence suggests that Ashkenazic Jews in
Europe who carried the allele for Tay-Sachs
disease had a survival advantage over those
who did not. Research this topic and write a
report that identifies the illness the TaySachs allele may protect against. How is this
story similar to what you have observed in
this investigation?
Rules of the Game
The “aa” genotype in offspring is lethal.
Offspring with this genotype will not
survive to reproductive age. Therefore two
“aa” parents cannot successfully mate. If
you and your mate are both “aa,” one of you
will need to obtain a new allele card (and
thus genotype) from the stock supply.
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normal mother
affected father
aa
Aa
a
A
a
sperm
Aa
eggs
a
affected child
Aa
aa
affected child
normal child
aa
normal child
Huntington disease, an autosomal dominant
condition, is a lethal disorder in which the brain
progressively deteriorates over a period of about
15 years. Its symptoms typically appear after age
35, which is often after the affected individuals
have already had children. Early symptoms include
irritability and mild memory loss, followed by
involuntary arm and leg movements. As the brain
deteriorates, these symptoms become more severe,
leading to loss of muscular co-ordination, memory,
and the ability to speak. Most people die in their
forties or fifties without knowing if their children
have inherited the mutant allele.
Incomplete Dominance
Figure 7.7 One example of autosomal dominant
inheritance. Carriers of the dominant allele are affected.
Although genetic disorders caused by autosomal
dominant alleles are very rare in human
populations, they continue to exist. Some of them
are caused by rare, chance mutations. In other
cases, symptoms arise only after affected
individuals have passed the age at which most of
them have had children. The Punnett square in
Figure 7.7 shows how an autosomal dominant trait
can be inherited.
Progeria is a rare disorder that causes an
individual to age rapidly. Progeria affects one in
eight million newborns and does not run in
families. This indicates that this very unusual
affliction results from a random and spontaneous
mutation of one gene. It also indicates that this
mutated gene must be dominant over its normal
partner, setting up a cascade of events that
accelerates the ageing of the individual.
SECTION
K/U Explain the difference between genetic
conditions and genetic disorders, and name one
example of each.
2.
C Explain how a disorder or abnormality can be
passed along by autosomal recessive inheritance.
4.
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REVIEW
1.
3.
K/U
The disease familial hypercholesterolemia (FH) is
caused by incomplete dominance. That is, the
heterozygote exhibits a phenotype somewhere
midway between both dominant and recessive
traits. Approximately one in 500 people are
heterozygous, inheriting a defective allele for a
gene that codes for the production of cell surface
proteins called LDL receptors. Circulating LDL
(low-density lipoproteins) cholesterols must bind
to these receptors in order to be taken up and used
by cells. With one defective allele, heterozygotes
produce only half the required receptors and
exhibit twice the normal blood cholesterol level.
Homozygous recessives (about one in 1 000 000
people) do not produce any receptors and can have
six times the normal blood cholesterol level. Over
time, circulating LDLs build up in artery walls and
eventually block them. This causes atherosclerosis,
which leads to heart attacks and strokes. While
heterozygous individuals may have heart attacks by
the age of 35, homozygous recessive individuals
who have the more serious form of the disease can
be stricken by a heart attack at the age of two years.
5.
I Predict why disorders caused by autosomal
dominant alleles continue to exist in the human
population. What evidence would you need to
support your claim?
6.
C Explain how DNA can be studied using gel
electrophoresis.
7.
MC What steps could you take to start building a list
of genetic characteristics for people in your class?
8.
I Explain some differences between the patterns
of inheritance observed in autosomal recessive
conditions versus autosomal dominant conditions.
What is meant by heterozygous advantage?
Can a recessive allele be eliminated from a
population? Explain.
K/U
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