Download Slide 1

CHAPTER 14
THE HUMAN GENOME
14-1 Human Heredity
Key Concepts
• How is sex determined?
• How do small changes in DNA cause genetic
disorders?
How do biologists go about studying human DNA?
•They use something
called a KARYOTYPE
•Biologists photograph
cells in mitosis, when
chromosomes are
easier to see. They cut
out the chromosomes
from the photographs
and group them
together in pairs
• Humans have a total of 46 chromosomes –
half (23) from mom and half (23) from dad
• Out of those 46, two are called SEX
CHROMOSOMES
– Determine an individual’s sex
• Females have two copies of
a larger X chromosome
• Males have one large X
and a smaller Y chromosome
• AUTOSOMES
– The other 44 chromosomes
• Females – 46XX
• Males - 46XY
• Look at the karyotype in your notes,
is this individual male or female?
–Male
•How is the X chromosome different
from the Y chromosome?
–The X chromosome is longer
• How is sex determined?
–All egg cells carry a single X
chromosome.
–However, half of all sperm cells
carry an X chromosome.
–This ensures that about half of
the zygotes will be 46XX and half
will be 46XY
Finish this Punnett Square to see how sex is determined
X
X
Y
X
X
X
XX
X
XX
Y
XY
XY
• How do biologists identify an inherited
trait that is controlled by a single
gene?
–They must establish that the trait is
actually inherited and not a result of
environmental influences
-They have to study how the trait
is passed from one generation to
the next
• PEDIGREE
– Shows the relationship within a
family; helps to study genetic
traits
– Can help parents understand the
probability of having a child with a
genetic disorder
Figure 14-3 A Pedigree
A circle represents
a female.
A horizontal line connecting
a male and female
represents a marriage.
A half-shaded circle
or square indicates
that a person is a
carrier of the trait.
A completely
shaded circle or
square indicates
that a person
expresses the
trait.
Go to
Section:
A square represents
a male.
A vertical line and a
bracket connect the
parents to their children.
A circle or square
that is not shaded
indicates that a
person neither
expresses the trait
nor is a carrier of
the trait.
• What do circles represent?
-Females
•What do squares represent?
-Males
•What does a horizontal line
represent? –Between a male and female
represents a marriage
•What does a vertical line represent?
–Connects parent to their children
• What does a circle or square that is
not shaded represent?
-That person does not express a trait
nor are they a carrier
•What does a fully shaded circle or
square represent?
-The person expresses a trait
• What does a half shaded circle or
square represent?
–The person is a carrier of the trait
•What is the sex of the last person in
the second row? Does that person have
the trait?
–Female; no
Pedigree analysis
• Pedigree analysis reveals Mendelian patterns in
human inheritance
– data mapped on a family tree
= male
= female
= male w/ trait
= female w/ trait
• POLYGENIC
– A trait controlled by many genes
• How can you find out where you get your good
looks from?
– This is actually rather difficult
– Many traits are polygenic like the shape of
your eyes or ears
– Many of your traits are only partly governed
by genetics – environmental influences
(nutrition, exercise) can affect how a trait is
expressed
What is your blood type?
• Why is it
important for a
doctor to know
your blood type
before they give
you a blood
transfusion?
–Using the wrong
blood type during
a transfusion can
be fatal
The best known blood groups are ABO
and Rh
• Rh
-Rh blood group is determined by a single
gene with two alleles –
–positive and negative
-Rh stands for rhesus monkey – this was
the first animal where they discovered
this factor
• The positive allele is dominant
–If you are Rh+/Rh+ or Rh+/Rh- you are
considered Rh positive
• The negative allele is recessive
– If you have two Rh- alleles you are
Rh negative
ABO
• a little more complicated
• There are three alleles IA, IB, and I
• Alleles IA and IB are codominant
• These alleles produce molecules known as
antigens that your immune system can
recognize on the surface of red blood cells
• If you have IAIA you only produce A
antigens etc. – see fig 14-4 p. 344
Figure 14-4 Blood Groups
Phenotype
(Blood Type
Go to
Section:
Genotype
Antigen on
Red Blood Cell
Safe Transfusions
To
From
• If you are homozygous ii you have no
antigen on your red blood cells this is
blood type O
• Typically nurses and doctors will use both
blood types like AB negative or O positive
• What happens if you give type A
blood to a type O patient?
–The immune system will recognize
the blood cells as foreign (they don’t
belong) because of the A antigens on
the cell’s surfaces. The immune
system will produce antibodies against
these blood cells and destroy them
• Why are type AB people called universal acceptors?
– They can accept any blood type
• Why are type O called universal donors?
– They can donate to any blood type
• What blood type do you think most blood banks want to
have on hand?
– Type O because is has no antigens and can be given to any
blood type without causing an antibody reaction
• If a woman with type O blood and a
man with type AB blood have children,
what are the children’s possible
phenotypes?
• Use a Punnett Square to answer
IA
i
i
IB
i
IA
IAi
IB
IBi
i
IAi
IBi
Genotypes: IAi and IBi
Phenotypes: Type A and Type B
Genetic Disorders-they are disorders that
are inherited in our genes
Autosomol
Disorders
caused by
Dominant alleles
Codominant
alleles
include
include
include
Huntington’s
disease
Sickle cell
disease
Galactosemia
Albinism
Cystic
fibrosis
Go to
Section:
Recessive
alleles
Phenylketonuria
Tay-Sachs
disease
Achondroplasia
Hypercholesterolemia
If there is a known genetic condition a doctor
may suggest a couple go through genetic
counseling to determine their risk of having a
child with an inherited genetic condition.
• A pedigree can help us understand the past
& predict the future
• Thousands of genetic disorders are
inherited as simple recessive traits
– benign conditions to deadly diseases
– albinism
– cystic fibrosis
– Tay sachs
– sickle cell anemia
– PKU
Genetic testing - may be done to determine if an
unborn child has a genetic disorder.
Example: Amniocentesis
Recessive diseases
• The diseases are recessive because the allele
codes for either a malfunctioning protein or
no protein at all
– Heterozygotes (Aa)
• carriers
• have a normal phenotype because one “normal”
allele produces enough of the required protein
Heterozygote crosses
• Heterozygotes as carriers of recessive alleles
Aa x Aa
female / eggs
male / sperm
A
A
a
AA
AA
Aa
Aa
A
Aa
a
A
a
Aa
Aa
aa
Aa
a
Albinism – homozygous recessive (aa)
Phenylketonuria – PKU
• People lack an enzyme to break down phenylalanine
• Phenylalanine is an amino acid found in milk and many
other foods
• If a child with PKU eats phenylalanine and it builds up
in their tissues – mental retardation occurs
• There is a test
• Treatment – the person must be on a low-phenylalanine
diet their entire life
• Caused by a recessive allele on chromosome 12
Tay-Sachs
• Primarily Jews of eastern European (Ashkenazi)
descent & Cajuns
– strikes 1 in 3600 births
• 100 times greater than incidence among
non-Jews or Mediterranean (Sephardic) Jews
– non-functional enzyme fails to breakdown
lipids in brain cells
• symptoms begin few months
after birth
• seizures, blindness &
degeneration of motor &
mental performance
• child dies before 5yo
Tay-Sachs disease
(continued)
• Caused by an allele found in Jewish
families with central and eastern
European ancestry
• Results in nervous system breakdown
and death in the first few years of life
• There is no treatment
• Parents can be tested ahead of time to
see if they are carriers
Dominant allele disorders
• Achondroplasia
– One type of dwarfism
– The person never reaches a height greater
than 4 feet 4 inches tall
– Arms and legs form disproportionately short
– 1 in about 10,000 people are affected
Huntington’s disease
• Causes progressive loss of muscle
control and mental function until
death occurs
• Symptoms don’t show until people
are in their thirties and forties
Codominant allele disorders
Sickle cell anemia
• Primarily Africans
– strikes 1 out of 400 African Americans
– caused by substitution of a single amino acid in
hemoglobin
– when oxygen levels are low, sickle-cell hemoglobin
crystallizes into long rods
– Due to this shape the cells are more rigid and they
tend to get stuck in capillaries causing blockages
– Causes physical weakness, brain damage, damage to
the heart and spleen
• deforms red blood cells into
sickle shape
• sickling creates pleiotropic
effects = cascade of other
symptoms
Sickle cell phenotype
• 2 alleles are codominant
– both normal & abnormal hemoglobins are
synthesized in heterozygote (Aa)
– carriers usually healthy, although some
suffer some symptoms of
sickle-cell disease
under blood oxygen
stress
• exercise
• Heterozygous people still have sickle
shaped red blood cells but not as many
• When the body destroys sickled cells, it
gets rid of the Malaria parasite at the
same time
• In regions where Malaria is a problem, it
is beneficial for people to be
heterozygous for sickle cell disease
Heterozygote advantage
Malaria
– single-celled eukaryote parasite spends part
of its life cycle in red blood cells
• Heterozygous people still have sickle
shaped red blood cells but not as many
• When the body destroys sickled cells, it
gets rid of the Malaria parasite at the
same time
• In regions where Malaria is a problem, it
is beneficial for people to be
heterozygous for sickle cell disease
• In tropical Africa, where malaria is common:
– homozygous normal individuals die of malaria
– homozygous recessive individuals die of
sickle cell anemia
– heterozygote carriers are relatively free of
both
Malaria, a serious parasitic disease that infects red blood
cells, is common in certain regions of Africa. People who
are heterozygous for sickle cell disease are generally
healthy and they are resistant to Malaria
Prevalence of Malaria
•High frequency of
sickle cell allele in
African Americans is
vestige of African
roots
Prevalence of Sickle
Cell Anemia
Cystic Fibrosis
• Common in people whose ancestors come from Northern
Europe
– strikes 1 in 2500 births
• 1 in 25 whites is a carrier (Aa)
• Recessive allele on chromosome number 7 the normal
allele codes for a membrane protein that transports Clacross cell membrane
• defective or absent protein channels cause high
extracellular levels of Cl• thicker & stickier mucus coats around cells
• mucus build-up in the pancreas, lungs, digestive
tract & causes bacterial infections
• Children with CF have serious digestive problems
• They produce thick, heavy mucous that clogs their
lungs and breathing passages
• Without treatment children die before 5;
with treatment can live past their late 20s
Normal Lungs
Chloride channel
Clairway
Na+
cells lining lungs
mucus secreting glands
Transports chloride
through protein channel
out of cell.
Osmotic effects:
H2O follows Cl-
Cystic fibrosis
damaged lung tissue
Clairway
Na+
cells lining lungs
thickened mucus
hard to secrete
bacteria & mucus
build up
Heterozygous Advantage
• Heterozygous people are unaffected
because they produce enough of this
protein to allow their tissues to
function properly
14-2 Human Chromosomes
Key Concepts
Why are sex linked disorders more common in
males, than in females?
What is nondisjunction, and what problems does
it cause?
• Look at page 341.
Which chromosomes are the largest?
1 and 2
Which chromosomes are the smallest?
18-22
Considering the chromosome sizes, how many bases might
chromosome 1 have if chromosome 22 has about 43
million bases?
About three times as many – 129 million
• Chromosome 21 and 22 are the smallest
human autosomes
• These were the first two chromosomes whose
sequences were discovered
– Chromosome 22 has 545 genes
• Problems with this chromosome
– genetic disorders are: an allele associated
with a form of leukemia and another
associated with neurofibromatosis (a tumorcausing disease of the nervous system)
• Chromosome 21 has 225
genes
• Genetic disorders are:
amyotrophic lateral
sclerosis (ALS) also
known as Lou Gehrigs
disease
– this disease causes a
progressive loss of
muscle control due to
the destruction of
nerves in the brain and
spinal cord
Recall:
• Genes located on the same chromosome
are linked, meaning they tend to be
inherited together
• Genes may be separated by recombination
(during crossing-over) in meiosis
• Look at p. 350 fig 14-12
• Which chromosome carries more genes?
The X chromosome
SEX-LINKED GENES
A gene located on the X or Y
chromosome
• More than 100 sex-linked genetic
disorders have been mapped to the X
chromosome
• The Y chromosome is much smaller and
appears to only carry a few genes
• Why are sex-linked disorders more
common in males than in females?
– Males have just one X chromosome.
Thus, all X-linked alleles are expressed
in males, even if they are recessive.
Colorblindness
• the person cannot see certain colors
• the human genes associated with colorblindness
are located on the X chromosome
• in males, a defective version of any one of
these genes produces colorblindness
• red-green colorblindness (cannot see green)
found in 1 out of 10 males in US but only 1 in
100 females
Can you see the numbers in each circle?
• Why do fewer females have
colorblindness?
– In order for a recessive allele,
such as the one for colorblindness,
to be expressed in females, there
must be two copies of the allele
• Pedigrees and pedigree Punnett squares
are used to trace genetic disorders
through families and to determine the
chances that future generations will have
the disorder
Figure 14-13 Colorblindness
Father
(normal vision)
Colorblind
Normal
vision
Male
Female
Daughter
(normal vision)
Son
(normal vision)
Daughter
(carrier)
Son
(colorblind)
Mother
(carrier)
Go to
Section:
• Why is the circle for the mother shaded only
halfway?
– She is heterozygous and is a carrier
• Would you expect the colorblind son to have
sons who are colorblind?
– No, the son can only pass the Y
chromosome to his sons
• What is the probability that the daughter who
is a carrier will have a colorblind child if she
marries a man with normal vision?
– 25%
Hemophilia
• A protein necessary for normal blood clotting is missing
• Two important genes carried on the X chromosome help
control blood clotting – a recessive allele in either of these
two genes may produce the disorder
• 1 in 10,000 males are born with it
• People with hemophilia can bleed to death from a minor cut
or could suffer internal bleeding from bumps or bruises
• These people are treated with injections of clotting
proteins
Duchenne Muscular Dystrophy
• Results in the
progressive
weakening and
loss of skeletal
muscle
• People rarely live
past adulthood
• 1 in 3000 males is
born with it
Calico cats
• Females have two X
chromosomes, but males
only have one
• If just one X
chromosome is enough
for cells in males, how
does the cell adjust to
the extra X chromosome
in female cells?
– Scientists have found
that in female cells,
one X chromosome is
randomly switched off
• A gene that controls coat color is located on
the X chromosome
• One X chromosome may have an allele for
orange spots and the other may have an allele
for black spots.
• In some cells on the cat’s body one X
chromosome (orange spots) is switched on
while the other X chromosome in those cells
is switched off
• Then in other areas the opposite occurs –
the black spots X chromosome switches
on and the other switches off
• Male cats have only one X chromosome so
they can only have spots of one color
• The turned off chromosome forms a
dense region in the nucleus known as a
Barr Body
• Barr bodies are not found in males
because their X is always turned on
• What is the sex of the cat in fig. 14-14?
– Female
Chromosomal abnormalities
• Incorrect number of chromosomes
– nondisjunction
• chromosomes don’t separate properly
during meiosis
– breakage of chromosomes
• deletion
• duplication
• inversion
• translocation
Nondisjunction
• Problems with meiotic spindle cause errors in
daughter cells
– tetrad chromosomes do not separate properly
during Meiosis 1
– sister chromatids fail to separate during Meiosis 2
– too many or too few chromosomes
2n
n-1
n
n+1
n
Alteration of chromosome number
Nondisjunction
• Baby has wrong chromosome number
– trisomy
• cells have 3 copies of a chromosome
– monosomy
• cells have only 1 copy of a chromosome
monosomy
trisomy
2n-1
2n+1
Human chromosome disorders
• High frequency in humans
– most embryos are spontaneously aborted
– alterations are too disastrous
– developmental problems result from
biochemical imbalance
• Certain conditions are tolerated
– upset the balance less = survive
– characteristic set of symptoms =
syndrome
Down syndrome
• Trisomy 21
– 3 copies of chromosome 21
– 1 in 700 children born in U.S.
• Chromosome 21 is the
smallest human chromosome
– but still severe effects
• Frequency of Down
syndrome correlates
with the age of the mother
Trisomy 21
Down syndrome & age of mother
Mother’s age
Incidence of Down
Syndrome
Under 30
<1 in 1000
30
1 in 900
35
1 in 400
36
1 in 300
37
1 in 230
38
1 in 180
39
1 in 135
40
1 in 105
42
1 in 60
44
1 in 35
46
1 in 20
48
1 in 16
49
1 in 12
Genetic testing
• Amniocentesis in 2nd trimester
– sample of embryo cells
– stain & photograph chromosomes
• Analysis of karyotype
Sex chromosomes
• Human development more tolerant of wrong
numbers in sex chromosome
• But produces a variety of distinct conditions in
humans
–
–
–
–
XXY = Klinefelter’s syndrome male
XXX = Trisomy X female
XYY = Jacob’s syndrome male
XO = Turner syndrome female
Klinefelter’s syndrome
• XXY male
– one in every 2000 live
births
– have male sex organs,
but are sterile
– feminine
characteristics
– tall
– normal intelligence
Klinefelter’s syndrome
Klinefelter’s syndrome
Jacob’s syndrome male
• XYY Males
– 1 in 1000 live male births
– extra Y chromosome
– somewhat taller than average
– more active
– slight learning disabilities
– delayed emotional immaturity
– normal intelligence, normal sexual
development
XYY Males
Trisomy X
• XXX
– 1 in every 2000 live births
– produces healthy females
• Why?
Turner syndrome
• Monosomy X or X0
– 1 in every 5000
births
– varied degree of
effects
– webbed neck
– short stature
– immature sterile
females
Turner syndrome
14-3 Human Molecular Genetics
Key Concepts
What is the goal of the human genome project?
What is gene therapy?
Bioethics and You
• As you become more aware of scientific
advances in genetics, you might realize that
with the ability to manipulate genes, there
comes responsibility.
• This ability provides an opportunity to
improve the lives of many people.
• But there is also a potential for errors or
intentional misuse of the technology.
Go to
Section:
• If two prospective parents suspect they
might be carrying recessive alleles for a
genetic disorder such as cystic fibrosis or
Tay-Sachs disease, how could they find out
for sure?
– Genetic tests have been developed
that can spot abnormalities in DNA.
Scientists can compare normal
sequences with these parents’ DNA to
see if they are carriers
• DNA FINGERPRINTING
– Analyzes sections of DNA that
have little or no known function but
vary widely from one person to the
next – this tool can identify
individuals
How to do DNA Fingerprinting
•
•
•
•
•
•
A sample of DNA with genes and repeats
(“junk DNA”) is taken
Restriction enzymes cut the DNA into
fragments containing genes and repeats
The DNA fragments are separated
according to size using gel electrophoresis
Radioactive “probes” showing where the
repeats are – this produces a series of
bands
This has been used since the 1980’s
It not only helps to convict criminals but has
also freed those who were wrongly accused
• HUMAN GENOME
– Our complete set of genetic
information
• What is the Human Genome Project?
– 1990 the US and other countries began
trying to sequence all human DNA
– This project was completed in 2003
– They have mapped 20,000 – 50,000 human
genes
– They know the sequence of 3 billion base
pairs
– Now that scientist know the entire human
genome they are trying to figure out how to
prevent certain genetic disorders
GENE THERAPY
The process of changing the gene that
causes a genetic disorder – it is
replaced by a normal working gene
Bone
marrow cell
Normal hemoglobin gene
Nucleus
Chromosomes
Bone
marrow
Genetically engineered virus
Go to
Section:
Food for thought
• Do you think it should be legal for
people to affect their children’s
characteristics?
• What will happen to the human
population if we gain the opportunity to
design our bodies?
Key Concepts Answered:
How is sex determined?
• All egg cells carry a single X chromosome
(23X). However, half of all sperm cells carry an
X chromosome (23X) and half carry a Y
chromosome (23Y). This ensures that just
about half of the zygotes will be 46XX and half
will be 46XY. Egg cells contain a single X
chromosome. Sperm cells contain either one X
chromosome or one Y chromosome.
How do small changes in DNA cause genetic
disorders?
• a small change in the DNA of a single gene
affects the structure of a protein, causing a
serious genetic disorder
Key Concepts Answered:
Why are sex linked disorders more common in
males, than in females?
• Males have just one X chromosome. Thus, all Xlinked alleles are expressed in males, even if they
are recessive.
What is nondisjunction, and what problems does it
cause?
• Nondisjunction causes gametes to have abnormal
numbers of chromosomes. If nondisjunction
occurs, abnormal numbers of chromosomes may
find their way into gametes, and a disorder of
chromosome numbers may result.
Key Concepts Answered:
What is the goal of the human genome
project?
• The Human Genome Project is an
attempt to sequence all human DNA.
What is gene therapy?
• In gene therapy, an absent or faulty gene
is replaced by a normal, working gene.