genetic discussion 3 (mutations, DNA damage, diseases) Flashcards
What type of mutation is most likely to cause
KNOCKOUT MUTATION of the gene
(i.e. cause TOTAL LOSS OF GENE FUNCTION)?
What are the causes of this mutation naturally?
A NONSENSE Mutation:
- C. BY CODON ==> STOP CODON
= This CAN OCCUR NATURALLY IN REPLICATION particularly when a
==> BASE IS ADDED or DELETED
==> causing a FRAMESHIFT MUTATION
*STOP CODON is incorporated early in the sequence then this may be called a null or knockout mutation as it COMPLETELY INACTIVATES THE GENE
Give an example of how a viral infection can be treated by using a DNA base analogue
= Herpes
==>Herpes are DNA viruses and ==>use the cell machinery to replicate ==> ACYCLOVIR looks like a BASE used for a growing DNA chain ==> acyclovir picked up by VIRAL POLYMERASE more than our own DNA polymerase more likely to ==>stop the growing viral DNA.
3*. What constitutes a silent mutation and how do these arise?
Silent mutations = mutation that
DOES NOT LEAD TO AN AA CHANGE
in the sequence of amino acids
that make up the genes protein.
This is bec.. THE CODE IS “DEGENERATE”
so a change esp 3RD BASE in a codon
may still lead to the SAME AA
4*. What common disease might arise in persons with
— defective NER process?
Explain your answer
*PROCESS nucleotide excision repair (NER)…
==> damaged bases are cut out
within a string of nucleotides
==> replaced with DNA
as directed by the undamaged TEMPLATE STRAND
*NER system used to ..
- remove PYRIMIDINE DIMERS
formed by UV radiation
- remove NUCLEOTIDES
modified by bulky chemical adducts.
Individuals with a defective NER process would be
at a HIGHER RISK OF SKIN CANCER.
==>bec.. NUCLEOTIDE EXCISION REPAIR (NER) process =
important mechanism that
==>REMOVES DNA DAMAGE = 2 Ts are fused
==>induced by UV LIGHT
==> NER is also damaged ==> SOS repair is used ==> SOS repair does NOT HAVE PROOFREADING >>> MORE mutations occur >>> leading ==> CANCER
What type of
— repair mechanism
would be used for a
—thymine dimer
and why?
*PROCESS nucleotide excision repair (NER)…
==> damaged bases are cut out
within a string of nucleotides
==> replaced with DNA
as directed by the undamaged TEMPLATE STRAND
*NER system used to ..
- remove PYRIMIDINE DIMERS
formed by UV radiation
- remove NUCLEOTIDES
modified by bulky chemical adducts.
thymine dimer =
==> 2 ADJACENT THYMINE BASES in the same DNA strand
==>BIND TOG
==>resulting in a thymine DIMER.
==>two bases that need repairing,
==>the (NER) mechanism is used
==>this cleaves the thymine dimer from the DNA strand ==>new DNA is synthesised to replace the dimer.
6*.
—How many nucleotides are
replaced with BER DNA repair
(base excision repair)
and which
—enzyme
would probably do this job?
- **difference between
- BER/mismatch repair
- NER nucleotide excision repair
BER/mismatch repair
= one nucleotide is replaced
NER nucleotide excision repair
= several nucleotides are replaced.
= 1 nucleotide is replaced.
==>mutated base is flipped out of helix
==>replaced with a non- mutated nucleotide
multiple enzymes are used but
= DNA POLYMERASE is crucial
*as it has proof reading ability.
Explain how
- –smoking causes cancer and
- -mutations in embryos
==>ERRORS IN APOPTOSIS
==>cause UNCONTROLLED CELL GROWTH
==> can cause TUMOURS
p53 gene = ACTS “the GUARDING OF THE CELL”
***MUTATION OF P53 gene
are commonly FOUND IN CANCER
==>BENZOPYRENE is a
POLLUTANT IN CIGARETTE SMOKE
==>acts as an ADDUCT (sticks to a cells DNA)
==> can cause MUTATION
==>Benzopyrene sticks to p53
==>STOPS IT from DOING ITS JOB (protecting cell)
==>benzopyrene ADDUCTS can STICK to SPERM & EGG DNA. tf person who obtained damage through smoking ==>TRANSFER MUTATIONS ==> to OFFSPRING
From slide 12.
Why can a knockout mutation be both
- a nonsense = CODON to STOP
- or a missense = 1 AA change (but NOT a stop)
but a missense mutation cannot be
- a nonsense mutation?
*** Missense mutation = 1 AA (not result in stop)
= change in one amino acid in a protein
arising from a point mutation in a single nucleotide.
***nonsense mutation = CODON > to STOP
= a codon is changed to a premature stop codon
that results in
“truncation” (Elimination of the N- or C-terminal)
of the resulting protein.
A Knockout mutation
= non functioning gene
- nonsense»_space;> no gene product (stopped early)
- missence»_space;> non-functional protein (same size)
A Missence Mutation
= still a gene product»_space;> non functional
=============== Nonsense ==> change of nucleotide ==> leads to an introduction of a stop codon. >>> truncation / cut short protein
Missense
==> change of nucleotide
==> leads to a different amino acid, BUT NOT STOP codon.
»> non functional protein
From slide 15 - hard.
In the crossover event in meiosis,
parts of mum and dad genes can swap chromosomes,
but the
- gametes still usually have only one copy of the gene.
How do the chromosomes ensure this happens?
In order for crossover to occur
- the genes must be VERY SIMILAR IN THEIR CODE.
crossover only occurs where there are
MATCHING ALLELES
From slide 19.
Huntington’s disease is an autosomal dominantly inherited disorder.
What do the words in bold tell us about the disease?
Autosomal - NOT A SEX CHROMOSOME
Dominant - you ONLY NEED ONE COPY
of this gene to have the disease
Cystic fibrosis is an
- autosomal recessive disorder.
What does this say about the
- genotype and
- phenotype of a sufferer?
= BOTH PARENTS MUST BE A CARRIER of the
DEFECTIVE GENE
to pass it off to their offspring.
Genotype: both copies of the defective gene must be present
Phenotype: only those individuals with both copies of the gene will have the phenotype of disease
From slide 27.
Why is AZT relatively harmless to replication in human cells?
***Zidovudine (ZDV), AKA azidothymidine (AZT) = an antiretroviral medication used to prevent and treat HIV/AIDS.
AZT is relatively harmless to replication in human cells because of the
= WAY IT IS PICKED UP WITHIN THE BODY.
T analog is in the body of a HIV positive individual
= viral HIV enzyme
is 1000 times more likely to pick up this T analog
(than by human cells)
==> AZT has been picked up by the HIV
==> inhibits the replication of the HIV virus
*by putting T analogue in place of thymidine (base)
- some side effects
- relatively harmless to human cells.
How does
UV radiation
damage DNA differently to
X-rays?
==> UV radiation ==> causing a Thymine Dimer *result of two T bases on the same DNA strand being stuck together.
The thymine dimer doesn’t necessarily damage the DNA
- more the ACTION OF TRYING TO UNBIND the T bases
CAUSES THE DAMAGE
==> X-ray causes
==> breaks to either one or both strands of DNA.
==> tf damage occurs when
- genes are deleted or
- attempted fusion of chromosomes occurs
as it is a complicated process
that could easily go wrong.
From slide 35.
How can a defective NER lead to skin cancer?
Defective NER is due to
==> the skin being overexposed to UV rays
==> NER mutates
then ==> the body has to resort to using an extreme form of repair, SOS = alternate polymerases ==> have no proofreading ability ==> create many errors 'MUTATIONS' in the DNA sequence.
Speculate on why a cell may not rely on base excision repair to fix UV damage?
BER Base excision repair
= used when only 1 MUTATED BASE
Thus BER could not be used on UV damage as it results in TWO Ts sticking together. (2 MUTATIONS)
==> NER must be used
==> if this is also damaged
==> then SOS.
Slide 36 – hard.
If SOS repair causes the mutations of UV damage, why did it evolve?
***SOS
= repairs severely damaged BASES in DNA
by base excision and replacement,
EVEN IF there is NO TEMPLATE to guide base selection.
This process is a LAST RESORT
for repair and is
OFTEN THE CAUSE OF MUTATIONS
evolved as an EMERGENCY RESPONSE
to repair severely damaged DNA.
==> when too much DNA is damaged by UV
==> too many thymidine dimers need to be replaced
==> SOS repair happens
»> SOS has NO PROOFREADING ability
»>resulting in many errors “MUTATIONS” in the DNA sequence.
This is okay for bacteria
- as they multiply rapidly
not so great in humans as
- it CAN LEAD TO CANCER
What is wrong with the enzyme that repairs UV damage?
Nothing wrong with NER
but the risk is that it ==> MAY ALSO BE DAMAGED ==> which calls in SOS ==> which does not have proofreading ==> can cause further mutations >>>leading to cancer
Why are older people more likely to develop cancer?
==> Random cell mutations accumulate over time
==> immune system becomes less effective as we age
==> tf ability to detect and fight cancer decreases
»> Accumulated mutations may involve
important TUMOUR SUPRESSOR GENES
Why don’t we have to test chemicals in animals when they are found to be non-mutagenic in bacteria?
==> test chem on bacteria ==> result no mutations seen >>> "non mutagenic chemical" ==> tf will also be a non mutagenic chemical for humans (just like in the bacteria)
bec..
None of the non-mutagenic chemicals
shown in bacteria
have been shown to cause cancers in humans
20*. Alleles that are not always expressed when present are called?
Alleles that are not expressed (but present)
= “Recessive”
recessive alleles can be expressed if
= 2 COPIES PRESENT
in the organism’s GENOTYPE
21*. Draw a punnet square for dwarfism inheritance from 2 heterozygous parents and explain the expected proportions of each genotype in the offspring. What are the expected proportions of the phenotypes?
Dwarfism inheritance: Genotype: = 25% homozygous dominant = 50% heterozygous dominant = 25% homozygous recessive
Phenotype:
As one of the infants dies at birth (homozygous dominant), the phenotype of the resulting offspring is
= 2/3 shortened stature
= 1/3 average height
(Danilla edit: I have corrected the way you must express the phenotype as the stillbirth does not give a proportion of children measurable by height. Also avoid the word normal and use average).
D d D DD Dd d Dd dd
22*. How many alleles code for hair colour?
= 10
“4 code for black, 1 code for red”
They will be a mix of
- -eumelanin (B and b) alleles = black
- -phomelanin (R and r) alleles = red
23*. If a person had the genotype BBbbbbbbRR what hair colour do you think they would have and why ?
LIGHT BROWN/ RED HAIR
==>d. one pair of functional eumelanin (B) allele
==>and the 3 pairs of non-functional eumelanin (b)
means that the person will have a light brown hair colour; functional eumelanin codes for = dark hair (black)
non-functional eumelanin codes for = blonde hair.
They will also have a
==>tinge of red hair
d. final pair of alleles being Phomelanin (R)codes =red hair
leaving only a small amount of red to be seen in the hair colour.
Explain how two brown-haired parents could have blonde offspring, given that 4 alleles control brown hair colour. Show the genotypes of the parents and the child.
Parent 1 BBBBbbbbrr
Parent 2 BBBBbbbbrr
Possible offspring gets bbbbr from both paranet s resulting in bbbbbbbbrr
What two genotypes lead to an O blood group phenotype?
To be O blood group phenotype you must receive a
= recessive O allele (from each parent)
giving you the genotype = OO.
Additionally if a person is Bombay blood group, they will be = genotypically A, B or AB, ==> but because of the mutation >>>they will appear O phenotype.
Is one gender
more likely to inherit an autosomal recessive disease?
If so, which?
NO
the disease is autosomal and tf NOT ON THE SEX CHROMOSOMES
so one gender is not more likely than the other.
Draw the punnet square if a
– person with cystic fibrosis and a
– cystic fibrosis carrier
had children. What are the expected genotype and phenotype proportions?
genotype cystic fibrosis = cc genotype (homozygous rec)
cystic fibrosis carrier = Cc genotype (heterozygous)
Genotype:
= 50% heterozygous carrier Cc,
= 50% homozygous recessive sufferer cc
Phenotype:
= 50% carrier
= 50% affected
C c c Cc cc c Cc cc
If Dwarfism is an autosomal dominant trait,
why is not more common?
==>dominant gene if INHERITED FROM BOTH PARENTS
|»_space;> death of the offspring.
Why are X-linked dominant disorders so rare?
Give the genotype of a male that could survive such a rare disorder?
Because every child inherits at least 1 X and thus would be affected.
Possible genotype of MALE THAT COULD survivor
= XXY
CF is an autosomal recessive disease. Women who have CF are fertile, while men who have CF are usually infertile. What might be a reason for this?
Male CF patients are infertile due to a blockage or absence of the sperm canal. This defect is called congenital bilateral absence of the vas deferens (CBAVD). The vas deferens is a long tube that carries sperm from the testicles through the male reproductive system. The absence of sperm in the semen makes it impossible to fertilize an egg.
Now that you have learnt about P53, why does smoking cause skin to look older than it actually does?
P53 required to bring on apoptosis, if it is
==> BLOCKED BY BENZENE then
==> many OLD CELLS REMAIN
==>instead of being apoptosed.
Use a punnet square to show how a person with
–blood type A and a person with
–blood type B can have a
child with blood type O.
What proportion of children will have a different blood type and what will be the blood types.
B O
A AB AO
O BO OO
==>2 HETERozygous parents (AO and BO) can
==> produce offspring with ANY of the 4 phenotypes
(AB, A, B, O).
The child had a
= 25% chance of being blood type O.
*25% chance the other offspring would be blood type AB, a 25% chance of being blood type A, and a 25% chance of being blood type B.
Use a punnet square to show the proportion of children likely to suffer
—-Huntington’s disease
if one parent is affected.
H = hunington’s disease allele
= 50% chance the child Huntington’s disease
= 50% chance the child will not have the disease.
h h H Hh Hh h hh hh
Draw a punnet square of the
—sex linked inheritance of haemophilia
of a carrier female and non-carrier male.
What proportion of children will have haemophilia?
= 25% (50% chance if the child is male).
will have haemophilia
XH Xh
XH XHXH XHXh
Y XHY XhY
