Topic 8A: Mutations + Gene Expression Flashcards
Mutation =
Any change to base sequence
Type of mutation: Substitution
One or more bases are swapped
Type of mutation: Deletion
one or more bases removed
Type of mutation: Addition
one or more bases added
Type of mutation: Duplication
one or more bases repeated
Type of mutation: Inversion
a sequence of bases are reversed
Type of mutation: Translocation
sequence of bases is moved from one location in the genome to another (can be movement within or between chromosomes)
Hereditary mutation
when gamete containing genetic disorder or type cancer is fertilised and present in new fetus
Mutagenic Agents =
increases rate of mutation
Examples of mutagenic agents
Ultraviolet radiation, ionising radiation and some chemicals and viruses
3 ways mutagenic agents increases rate mutations
- Acting as a base
- Altering bases
- Changing structure of DNA
Mutagenic agent: acting as a base
chemicals called Base Analogs can substitute for a base during DNA replication, = substitution mutation
Mutagenic agent: Altering bases
some chemicals can delete or alter bases
Mutagenic agent: Changing the structure of DNA
some types of radiation can change the structure of DNA which causes problems during DNA replication
Acquired mutations =
mutations that occur in individual cells after fertilisation (adulthood)
Uncontrolled cell division caused by
mutations in genes that control the rate of cell division
Tumours =
mass of abnormal cells
2 types of gene that control cell division
- tumour suppressor genes
2. proto-oncogenes
When tumour suppressor genes act normally =
slow cell division by producing proteins that stop cells dividing or cause self destruct
When mutation occurs in tumour suppressor gene
becomes inactivated - protein isn’t produced. Cells divide uncontrollably = tumour
When proto-oncogene acts normally
stimulate cell division by producing proteins that make cells divide
When mutation occurs in proto-oncogene
gene becomes overactive- stimulates cells divide uncontrollably = tumour
Mutated proto- oncogene called
oncogene
Malignant tumours =
cancerous - grow rapidly and invade and destroy surrounding tissues
cells can break off tumour and spread to other parts of the body in bloodstream or lymphatic system
Benign tumours =
not cancerous - grow slower and covered by fibrous tissue that stop cells invading other tissues
Harmless but can cause blockages and put pressure on organs
6 differences between tumour cells and normal cells
- irregular shape
- nuclues larger + darker (sometimes more than 1)
- dont produce all proteins needed to function
- different antigens on surface
- dont respond to growth regulating processes
- divide by mitosis more often
Abnormal methylation of cancer- related genes can cause
tumour growth
Methylation =
adding a methyl group
Methylation of DNA is an important method of
regulating gene expression - can control if gene transcribed and translated
Hypermethylation =
too much methylation
Hypomethylation =
too little methylation
When tumour suppressor genes are hypermethylated
genes are not transcribed - so proteins they produce to slow cell division aren’t made
Hypomethylation of proto -oncogenes
causes them to act as oncogenes increasing the production of the proteins that encourage cell division uncontrollably
Increased exposure to oestrogen increases
woman’s risk to devloping breast cancer
and menstaration earlier or menopause later
Oestrogen can stimulate
certain breast cancer cells to divide and replicate- increases chance of mutations and therefore chances of cancerous cells
Problem with oestrogen stimulating cancerous cells
increases the formation of tumours
impact of oestrogen on the DNA of certain breat cells
can introduce mutations directly into the DNA -increasing chances of cancerous cells
Forms of risk factors:
genetic and environmental
Genetic factors =
some cancers linked w/ specific inherited alleles
-if that allele inherited you most likely have get that cancer but not always
Environmental factors =
exposure to radiation, lifestyle choices (like smoking + alcohol + high fat diet) linked to increased chance of come cancers
Why data on varaitions difficult to interpret
some characteristics can be affected by many different genes (polygenic) and many environmental factors - difficult to know which has the greatest effect
cancer caused by
mutations in proto-oncogenes and tumour suppressor genes
how knowing exactly how a cancer works helps in 3 forms of prevention
1- possible to screen for mutation in person’s DNA
2- preventative steps e.g. mastecomy ( removing of the breasts) or more frequent screenings - early detection
3- knowing more about a mutation= more scientific tests can be developed for more accurate diagnosis
How knowing exactly how a cancer works helps in 3 forms of treatment and care
1- treatment for cancer can be different for different mutations so can be useful for developing drugs to effectively target
2- some cancers need more aggressive treatments - so helps produce best treatment plan
3- genetic therapy used to treat cancers caused by mutations
Genetic therapy =
faulty alleles in person’s cells are replaced by working versions
Totiponent stem cells =
able to mature into any type of body cell
Multicellular organisms made up from
many diff cell types that are specialised to their function
all have some form of stem cell
All specialised cells original come from
stem cells
Stem cells =
unspecialised cells that can develop into other types of cells which then become specialised
Stem cells found in
- the embryo (where they become specialised cells needed to form a fetus)
- in some adult cells (where become specialised cells that need to be replaced)
Totipotent stem cells only present in
mammals in the first few cell divisions of an embryo
After the first few cell divisions embryonic stem cells become
pluripotent- can still specialise into any cell in the body except the cells that make up the placenta
Stem cells in adult mammals are either
multipotent stem cells
unipotent stem cells
Multipotent stem cells =
+ example
able to differentiate into a few different type of cell e.g. both red and white blood cells formed from multipotent stem cells found in the bone marrow
Unipotent stem cells =
+ example
can only differentiate into one type of cell e.g. only one type unipotent stem cell that can divide to produce epidermal skin cells - make up outer layer of your skin
stem cells become specialised because
during development the only transcribe and translate part of their DNA
Stem cells all contain the same
genes but not all are transcribed and translated (expressed)
mRNA is only transcibed from
specific genes
mRNA translated into
proteins that modify the cell - determine the cell structure + control cell processes (e.g. expression of some genes)
Changes to cell due to proteins makes cells
specialised
changes are difficult to reverse
so once specialised cell stays specialised
Red blood cells are produced from
a type of stem cell in the bone marrow- contains lots haemoglobin and no nucleus - to make more room for haemoglobin
Red blood cells stem cells produce new cell in which
genes for haemoglobin production are expressed
and other genes which remove the nucleus are expressed too
Cardiomyocytes =
heart muscle cells that make up alot of the tissue in our hearts
made from unipotent stem cells
Recent research has found that our hearts have
regenerative capability
When can the heart become damaged
by a heart attack or with old age
Old or damaged cardiomyocytes can be replaced by
new cardiomyocytes derived from a small supply of unipotent stem cells in the heart
The conflicting opinions around cardiomyocytes placements
- Some believe process really slow + possible some cardiomyocytes are never replaced throughout a lifetime
- others think occur very quickly so every cardiomyocytes in heart replaced several times in a lifetime
Stem cells can be used to treat
human diseases
Bone marrow transplants used
to replace faulty bone marrow in patients tat produce abnormal blood cells because the stem cells can become specialised to form any type of blood cell
How stem cells in transplanted bone marrow works
they divide and specialise to produce healthy blood cells
Bone marrow transplants have been successful in treating
leukaemia (a cancer of the blood or bone marrow) + lymphoma (cancer of the lymphatic system)
Genetic disorders that stem cell therapies treat
sickle cell anaemia + severe combined immunodeficiency (SCID)
People with SCID have
poorly functioning immune system as their white blood cells are defective so they can’t defend against infections (can’t identify + destroy microorganisms)
Scientists are researching in using stem cell therapies in
- spinal cord injuries - replace damaged nerve tissues
- Heart disease + damage caused by heart attacks
- Bladder conditions -stem cells could be used to grow whole bladders, which then implanted into patient
- Respiratory diseases - donated windpipes can be stripped down to their simple collagen structure + covered w/ tissue generated by stem cells
- organ transplants - organs can be grown from stem cells to provide new organs or ppl on donor waiting list
Benefits on stem cells
- can save many lives e.g. ppl on organ transplant list
- improve the quality of life for many ppl - stem cells could be used to replace damage cells in the eye for the blind
Three main potential sources of human stem cells
- Adult tissues
- Embryos
- in labs
Adult stem cells obtained by
a simple operation w/ very little risk but quite uncomfortable
Adult stem cells vs embryonic stem cells
Adult stem cells aren;t as flexible - can only specialise into a limited range of cells- not all body cell types (multipotent)
Embryonic stem cells obtained from
embryos at an early stage of development
Embryonic stem cells:
embryos created in lab using
vitro fertilisation (IVF)- eggs cells fertilised by sperm outside the womb
Embryonic stem cells:
Once embryo 4/5 days old
stem cells removed and rest of embryo destroyed
How many times can embryonic stem cells divide
unlimited number of times + develop into all types of body cells (pluripotent)
iPS Cells =
induced pluripotent stem cells
iPS cells created in
labs
process = “reprogramming” specialised adult body cells so they become pluripotent
iPS Cells:
what happens when adult cells are reprogrammed
they are made to express a series of transcription factor that are normally associated w/ pluripotent stem cells.
Transcription factor causes adult body cell to express genes that are associated with pluripotency
iPS Cells:
how transcription factor introduced to adult cells
by infecting them with specially- modified virus
virus has the gene coding for the transcription factor w/in its DNA
when virus infects the adult cell the genes are passed in to the adult cell’s DNA - then able to produce the transcription factors
Research being done around iPS cells
to see how similar they actually are to true pluripotent embryonic stem cells before can be utilised properly
Ethical issues around using embryonic stem cells
1- destruction of embryo that could be a fetus in the womb
2- at moment fertilisation an individual has right of life- wrong to destroy
Why people object less eggs that aren’t fertilised by sperm cell but artificially activated
cells couldn’t survive past a few days + wouldn’t produce a fetus in a womb
pros and cons of only using adult stem cells
production doesn’t destroy an embryo
but can’t develop into all the specialised cell types that embryonic stem cells can
Pros of induced pluripotent stem cells
- have the potential to be as flexible as embryonic stem cells but from adult tissue
- cells could be made from patient’s own cells - genetically identical so used to grow new tissue or organ that body wouldn’t reject
Transcription =
when gene is copied from DNA into messenger RNA using enzyme RNA polymerase
All cells in an organism carry the same
genes (DNA) but the structure + function of different cells varies cause not all expressed
Transcription of genes controlled by
protein molecules called transcription factors
How transcription factors work
- move from cytoplasm to nucleus
- in nucleus they bind to specific DNA sites near start of target genes (genes they control expression of)
- control expression by controlling rate of transcription
2 forms of transcription factors
Activators - stimulate or increase the rate of transcription
Repressors - inhibit or decrease rate of transcription
both either help or prevent RNA polymerase from binding
Oestrogen =
+ how it affect transcription
a steroid hormone that can bind to transcription factor called an oestrogen receptor forming oestrogen- oestrogen receptor complex
What happens when oestrogen- oestrogen receptor complex formed
complex moves from the cytoplasm into the nucleus where it binds to specific DNA sites near the start of target gene - can be activator or repressor depending on type cell and target gene
In eukaryotics gene expression affected by
RNA interference (RNAi)
RNAi =
small, double standed, non coding RNA molecules that stop mRNA from target genes from being translated into proteins
Molecules involved in RNAi =
small interfering RNA (siRNA)
microRNA (miRNA)
How siRNA in eukaryotes and miRNA in plants work
5 steps
- Once mRNA has been transcribed it leaves the nucleus for the cytoplasm
- in cytoplasm double stranded siRNA associates w/ several proteins + unwinds
- single strand binds to target mRNA- bases of siRNA complementary to target mRNA
- proteins associated with siRNA cut the mRNA into fragments so no longer can be translated
- fragments move into a processing body - contains tools to degrade them
2 difference between miRNA and siRNA
- in mammals miRNA not fully complementary to target mRNA - less specifc than siRNA so may target more than 1 mRNA molecule
- miRNA protein complex physically blocks the translation of target mRNA
How miRNA works
- it associates with proteins + binds to target mRNA in the cytoplasm
- miRNA- protein complex physically blocks the translation of target mRNA
- mRNA moved into processing body where either stored or degraded
if stored it can be returned + translated at another time)
E. coli =
a bacterium that respires glucose but can use lactose if glucose not available
Response of E.coli if lactose present
makes an enzyme (β- galactosidase) to digest
Transcription factor that controls the production of the β- galactosidase enzyme
lac repressor
Responses of the lac repressor if lactose present or not
Not - lac repressor binds to the DNA at the start of the gene- stopping transcription
Present- lactose binds to lac repressor - stopping it binding to the DNA so gene transcribed
In eukaryotics epigentic control can determine
whether gene is switched on or off - whether gene transcribed or translated
How epigentic control works
through attachment or removal of chmeical groups (aka epigenetic marks) to or from DNA or histone proteins
Epigentic marks alter
how easily it is for enzymes + their proteins needed for transcription to interact w/ + transcribe the DNA
but don’t alter DNA base sequence
Organisms inherit DNA base sequence from
their parents
When are most epigenetic marks on DNA removed
between generations but some escape the removal process and are passed on to offspring
Epigenetic changes to gene expression due to
its role in lots of normal cellular processes or changes in the environment
2 forms of epigenetic control
methylation + acetylation
Methylation process
Methyl group attached to the DNA coding for a gene - always at a CpG site
increased methyation changes the DNA structure so that the transcriptional machinery (enzymes, proteins etc) can’t interact with the gene so not expressed
CpG site =
where cytosine and guanine base are next to each other in the DNA linked by phosphodiester bond
Histones =
proteins that DNA wraps around to form chromatin, which make up chromosomes
Process decreased acetylation of histones
when acetyl group removed from the histone
chromatin becomes highly condensed + genes in DNA can’t be transcribed because transcriptional machinery can’t physically access them
HDAC enzymes =
histone deacetylase enzymes that are responsible for removing the acetyl groups
Epigenetics can play a role in the development of what syndromes
Fragile X syndrome
Angleman’s syndrome
Prader - Willi syndrome
+ many others
Fragile X syndrome =
a genetic disorder that can cause learning + behavioral difficulties as well as characteristic physical features
Fragile X syndrome: caused by
a heritable duplication mutation in a gene on the X chromosome called FMR1 resulting in a short DNA sequence CGG being repeated more times than usual
Fragile X syndrome:
impact of the repeating CGG sequence
lots more CpG sites in the genes than usual
More CpG sites = increased methylation of gene which switches it off
because gene switched off the protein that it codes for isn’t produced - causing symptoms of the disease
Why are we able to develop drugs to counter the epigentic changes?
they are reversible
Example of how drugs used stop DNA methylation
azzacitidine is used in chemotherapy for types of cancers that are caused by increased methylation of tumour supressor genes
Example of how drugs used stop decreased acetylation
HDAC inhibitor drugs e.g. romidepsin inhibit the activity of histone deacetylase enzymes so genes can be transcribed
Problem with developing drugs to counteract epigentic change
these changes take place normally in a lot of cells so important that drug is specific as possible to target dividing cells not normal body ones
Phenotype =
a characteristic of an organism that’s a result of the organism’s genotype + the interaction of its geneotype with the environment
2 examples of phenotypes being influenced by both genes + environment
overeating vs antioxidant levels in berries
Overeating:
due to environmental factor
increased availability of food in developed countries
Overeating:
due to genetic food factor
consumption increases brain dopamine levels in animals
once enough dopamine released people stop eating
research found ppl w/ one particular allele had 30% less dopamine receptor so more likely to overeat
Antioxidant levels in berries:
due to genetics factor
scientists found that different berries produced by different species contained different levels of antioxidants
Antioxidant levels in berries:
due to environmental factor
same species of berries grown in different environments produced very different levels of antioxidants
What are twin studies
studies used to determine if a phenotype is due to environmental or genetic factors
Why identical twins used for studies
they are genetically identical so any differences in phenotype must be due to environmental factors
if characteristic is very similar genetics is the larger influence
if characteristic very different environment is the larger influence
Practicality of data from twin studies
large sample size (pairs of twins) so better for drawing a valid conclusion based on a small sample size - more representative of the population
