Download 1-HumanGen Mutations

Human Genetics &
Inheritance Patterns
• In the space below list a number of differences
and similarities found among humans.
Differences:
Similarities:
• You may be able to list more similarities
than differences.
• Many (but not all) of the features we listed
are genetic mutations.
Note to me…
• Do the taster/non-taster lab!
Mutations
• We have learned that DNA is responsible
for the production of proteins that direct an
organism’s metabolism and development.
• What would happen if there were changes in our DNA?
• On a rare occasion it may result in NEW
PHENOTYPES.
• A change in DNA is called a MUTATION
• These changes can affect an entire
chromosome or specific genes.
Any cells in our bodies are subject to mutations.
– Mutations in our SEX CELLS (egg or sperm) are
called GERM CELL MUTATIONS.
• These mutations do not affect the organism but
are passed to offspring.
• Most of the mutations that occur in germ cells
are lethal and do not allow the individual to
develop past the zygote stage.
• Mutations that occurs in other body cells
are called SOMATIC MUTATIONS .
These mutations are passed to daughter
cells through mitosis.
• These mutations do not affect the offspring
of the affected individual.
CHROMOSOMAL MUTATIONS:
• During cell division mutations may occur in
chromosomes. There are four types of
chromosomal mutations:
1. DELETION
• 2. INVERSION
• 3. TRANSLOCATION
• 4. NONDISJUNCTION
__Deletion_ :
• When a piece of the chromosome breaks
off. This results in the information on that
chromosome piece being lost.
__INVERSION____ :
• When a piece breaks off from a
chromosome and reattaches itself to the
chromosome in reverse order.
_TRANSLOCATION:
• When a broken piece attaches to a nonhomologous chromosome.
Nondisjunction
• A fourth type of chromosomal mutation is
called NONDISJUNCTION .
• This occurs when a replicated
chromosome pair fails to separate during
cell division.
• The daughter cells will result in one having
an extra copy of a chromosome and the
other cell lacking that chromosome
entirely.
GENE MUTATION:
• Scientist have found several mutations
that can occur in the DNA sequence.
• If the mutation only affects one nitrogen
base is called a POINT MUTATION.
• If one nitrogen base is replaced by another
nitrogen base the DNA may code for
different AMINO ACID .
– If one nitrogen base is added or deleted a
FRAME SHIFT MUTATION occurs. This
usually results in the inability of the DNA to
code for the correct amino acid.
MUTAGENS:
Some mutations happen by CHANCE.
There are other times when mutations are caused by MUT
environmental factors that result in that damage of DNA st
• A few well known mutation causing factors
are :
– cigarette tars,
– asbestos, and
– viruses.
– Radiation is also an environmental factor that
causes mutations in both germ and somatic
cells.
Spontaneous vs Induced
Mutations:
• All mutations are described as either
spontaneous or induced.
• We have already discussed the mutations
that are induced.
• Spontaneous mutations are considered
as those that arise in nature. No specific
agent other than natural forces is
associated with their occurrence.
• These mutations are assumed to arise
randomly as in changes in the nucleotides
sequence of genes.
• All mutations have a cause , but some
mutations occur in the absence of
mutagens, or mutation-causing agents.
Some of these mutations are the result of
miscues of the DNA REPLICATION
MACHINERY.
Sometimes the proofreading mechanism
fails and the mistake is not caught.
SPONTANEOUS MUTATIONS
• These type of mutations can occur in
several ways:
– (1) As DNA is replicating, mistakes are
made on occasion that go uncorrected.
– (2) The bases in the DNA template strand
or in the newly inserted nucleotide can
shift to an alternate form that base-pairs
incorrectly.
– (3) Too many or too few bases can be
inserted , causing frame-shift mutations.
CHEMICAL MUTAGENESIS
Induced Mutatuions
• Different chemicals induce different kinds
of DNA damage.
• Nitrous acid and bisulfite cause
deamination
– (the removal of an amino group [NH2] that
converts cytosine to uracil) of bases.
RADIATION- INDUCED MUTATIONS
• Ultraviolet, gamma, and
X-radiation are the
common types of
mutagenic radiation.
• Ultraviolet radiation is
relatively week so the
damage it causes is
relatively modest: it
cross-links adjacent
pyrimidines on the same
DNA strand,
– Forming a dimer, usually
a THYMINE DIMER.
What’s a dimer? (FYI only, not in notes)
• A dimer is a chemical or biological entity
consisting of two subunits called monomers,
which are held together by either intramolecular
forces (covalent bonds) or weaker
intermolecular forces.
• Molecular dimers are often formed by the
reaction of two identical compounds
• An example of an intermolecular or physical
dimer is acetic acid wherein hydrogen bonds
hold the two molecules together. The water
dimer is another such dimer.
• This blocks DNA
replication because
the replication
machinery cannot tell
which bases to insert
opposite the dimers.
– Other times an alternate
form of a nitrogen base
is used that bonds with
the alternate form of
nitrogen bases.
– Example there are two
forms of Thymine one
will bond with the usual
Adenine and the other
form will bond with
Guanine:
• Replication sometimes proceeds anyway
and bases are inserted at random .
• If these are the wrong bases, a
mutation results.
The kind of radiation that is most damaging to
DNA has a wavelength of about 260 nm,
– which is not surprising since this is the wavelength
of radiation that is most absorbed most strongly by
DNA.
– This type of radiation is also abundant in sunlight,
so most forms of life are exposed to this type of
radiation to some extent.
Radiation:
– This type of mutation explains why sunlight can
cause skin cancer.
– We have a shield from this type of radiation.
– The natural shield is the OZONE layer in the earth’s
upper atmosphere. This ozone absorbs the bulk of
such radiation.
Gamma and X rays.
• Gamma and X rays
have more energy
that ultraviolet
radiation. These
types of radiation
can interact directly
with DNA molecule.
These types of
radiation can cause
the DNA to break
apart.
Effects on Organism
• Scientist also
classify mutations on
the basis of their
effect on the
organism:
– 1. Morphological
trait mutations:
• These mutations
affect the morphology
or shape of the
organism:
– 2. Biochemical mutations:
These mutations affect
how an organism
accomplishes nutrition.
One example is the
inability of an organism to
synthesize an amino
acid.
• Also these types of
mutations may affect an
organisms chemical
processes such as gas
exchange: i.e. sickle cell
anemia.
• 3. Lethal mutations: these
mutations will cause the
death of the organism.
– One example of a lethal
mutation is Tay-Sachs or
Huntingtons disease.
•
Sometimes the lethal
mutations will cause
immediate death
• or as in the above
mentioned disease death
may come at a later time in
the life of the human.
Morphological Mutations:
• Complex multicellular organisms carrying
• MORPHOLOGICAL MUTATIONS (visible
mutations), can usually be distinguished from
wild-type (most common variant of a gene).
–
–One example , albino mammals have a
mutation in a gene that is responsible for
dark coat (or skin) pigment.
–The mutation
is usually in the
gene that
codes for
TYROSINASE,
the key
enzyme that
leads to the
production of
MELANIN the
black pigment
in hair, eyes,
and skin.
• A mutated
tyrosinase gene
may produce no
active enzyme, so
no melanin can be
made.
• As a result humans
have very fair skin
and light blue eyes,
albino mice have
white fur and pink
eyes.
LETHAL MUTATIONS:
• Some mutations are so severe
that an organism carrying them
cannot survive at all.
• These types of mutations are
called LETHAL mutations.
• When a genetic defect causes
100% mortality it is termed lethal
allele.
Lethals Cont.
• Lethals are generally recessive resulting
in the death of the zygote that is
homozygous recessive.
• n 1904 French geneticist Lucien Cue’not
carried out crosses on coat color in mice.
• He obtained results that were not consistent wi
Mendelian predictions.
• He observed that yellow body color alleles were
dominant. When he crossed two heterozygous
yellow mice he observed 2:1 ratio of yellow to wil
type (brown- agouti). What ratio did he expect:
• 3:1 Wild to yellow
• He learned that all the Homozygous yellow
mice died in utero.
• Histological observations validated this
conclusion which demonstrated 1/4 of the
embryos from yellow x yellow crosses
failed to develop.
• This demonstrates that lethal mutations
in diploid organisms are recessive .
• If one parent contributes a defective
gene for an essential protein and the
other contributes a wild-type gene, the
latter will usually allow the cell to
make enough protein to compensate.
• It is only when two defective genes
come together in a individual that
lethality results.
Conditional Mutations:
• There are certain mutations that can be lethal
under certain conditions.
• These mutations are called CONDITIONAL
LETHALS.
• Temperature Sensitive:
– There are certain mutations called
TEMPERATURE-SENSITIVE (or “ts”)
mutations.
• This mutation allows for growth at low
temperatures but not at normal growth
temperatures.
• Lethality in this case is conditional on
temperature.
• It is important to realize that it is the
PROTEIN PRODUCT that is
temperature sensitive, NOT THE GENE
ITSELF.
• This type of mutation creates an altered
protein that is easily DENATURED. (EGG
WHITE).
• This type of mutations can be observed in
humans.
– CYSTIC FIBROSIS is caused by a mutant gene
whose protein product cannot fold properly at
normal body temperature, so it remains
inactive.
– At lower temperatures it functions normally.
Conditional without lethality
• Genetic mutations can be
conditional without being
lethal.
• One example is Siamese
cats.
– These animals have a
mutation in the gene for
DARK coat color.
• Siamese cats have dark
patches on their feet ,
faces and ears can you
explain this mutation.
• Patches on their feet,
faces , and ears are
normal where the
temperature is somewhat
lower than the rest of the
body
• where the protein has
been denatured.(lighter in
color)
MISSENSE and NONSENSE
MUTATIONS
• Many point mutations are MISSENSE
MUTATIONS, in which a base change
alters the sense of a codon from one
amino acid to another.
– This causes an improper amino acid to be
inserted into the protein product of the
mutated gene. for example a missense
mutation might change the proline codon
CCG to ARGININE codon CGG. .
• An example of such a
defect is SICKLECELL DISEASE, a true
genetic disease.
• People who are
homozygous normal
for this condition have
normal looking red
blood cells when their
blood is rich in oxygen.
• The shape of normal
cells is disc shape that
is concave.
When people with this disorder exercise there is a
depletion of oxygen in their blood this creates a
change in the morphology of their red blood cells.
The sickling is caused when mutated hemoglobin
precipitates under low oxygen conditions.
• The red blood cells forms a
crescent (sickle) shape.
• The sickle cells cannot fit
through tiny capillaries so they
clog and rupture the
capillaries.
• This causes internal bleeding
and pain. The sickle blood
cells also burst and leave the
patient ANEMIC.