8A - Mutations and Gene Expression Flashcards
What is a mutation?
A change to the base sequence of DNA in an organism.
What causes mutations?
Errors during DNA replication.
What can increase the rate of mutation?
Mutagenic agents
What are the different types of mutation?
- Substitution
- Deletion
- Addition
- Duplication
- Inversion
- Translocation
In mutations, what is substitution?
When one or more bases are swapped for another.
e.g. ATGCCT becomes ATTCCT
In mutations, what is deletion?
When one or more bases are removed.
e.g. ATGCCT becomes ATCCT
In mutations, what is addition?
When one or more bases are added.
e.g. ATGCCT becomes ATGACCT
In mutations, what is duplication?
When one or more bases are repeated.
e.g. ATGCCT becomes ATGCCCCT
In mutations, what is inversion?
When a sequence of bases is reversed.
e.g. ATGCCT becomes ACCGTT
In mutations, what is translocation?
When a sequence of bases is moved from one location in the genome to another.
Is translocation always within the same chromosome?
No, it can be between chromosomes too.
How does a mutation cause a protein to be non-functional?
- Mutation is a change in the DNA base sequence
- This may change the amino acids that that DNA codes for
- This means that the amino acid sequence is different
- Therefore, the bonds formed are different, so the tertiary structure is different
- This makes the protein non-functional
Give an example of a mutation causing a genetic disorder.
Cystic fibrosis
Give an example of a mutation increasing the likelihood of developing a cancer.
BRCA1 gene mutations can increase the risk of breast cancer.
What is a hereditary mutation?
A mutation that is passed through gametes to the next generation.
Remember to revise the AS mutation flashcards.
Do it. Also see pgs 194-195.
What are mutagenic agents?
Factors that can increase the rate of DNA mutation.
What are the 3 ways in which mutagenic agents work?
1) Acting as a base
2) Altering bases
3) Changing the structure of DNA
How do some mutagenic agents work by acting as a base?
- Chemicals substitute for a base in DNA replication
* This changes the base sequence
What is the name for mutagenic agents that substitute for a base?
Base analogs
Give an example of a base analog.
- 5-bromouracil
- It can substitute for thymine, but pair with guanine instead
- This effectively changes the DNA base sequence
How do some mutagenic agents work by altering bases?
- Chemicals delete or alter bases
* This changes the DNA base sequence
Give an example of a mutagenic agent that alters bases.
- Alkylating agents
- These add an alkyl group to guanine, which changes the structure so it pairs with thymine (instead of cytosine)
- This changes the effective bass sequence
How do some mutagenic agents work by changing the structure of DNA?
- Radiation changes the structure of DNA
* This causes problems during DNA replication
Give an example of a mutagenic agent that changes the structure of DNA.
- UV radiation
- This can cause adjacent thymine bases to pair up together
- This changes the effective DNA base sequence
What are acquired mutations?
Mutations that occur in individual cells after fertilisation.
What are the two types of DNA mutations?
- Hereditary
* Acquired
When are DNA mutations the worse?
When they occur in genes that control the rate of cell division. This can cause uncontrolled cell division.
What is a tumour?
A mass of abnormal cells caused by a cell dividing uncontrollably.
What is the difference between a tumour and a cancer?
A cancer is a tumour that invaded and destroys surrounding tissue.
What are the two types of gene that control cell division?
- Tumour suppressor genes
* Proto-oncogenes
What is a proto-oncogene?
A gene that stimulates a cell to divide when growth factors attach to receptors on the membrane.
What is an oncogene?
A mutated proto-oncogene which is permanently switched on.
How can a mutation in a proto-oncogene cause cancer?
- Mutations or hypomethylation causes the gene to become overactive
- A mutated proto-oncogene is called an oncogene
- This means that the proteins required to stimulate cell division are produced in abundance
- Cells divide uncontrollably
What are the two types of tumour?
- Malignant
* Benign
What are malignant rumours?
- Cancers
- They grow rapidly and invade and destroy surrounding tissues
- Cells can break off and spread to other parts of the body through blood or lymph
Why are benign tumours?
- Not cancerous
- They grow slowly
- Are often covered in fibrous tissue that atoms cells invading other tissues
Are benign tumours dangerous?
No, but they can cause blockages and put pressure on organs.
How do tumour cells look different to normal cells? (6)
1) Irregular shape
2) Larger and darker nucleus
3) Don’t produce all the proteins required for normal function
4) Different antigens
5) Don’t respond to growth regulating processes
6) Divide more frequently
What type of epigenetics is involved in cancer?
Methylation
What is the effect of hypermethylation?
Reduced transcription
What is the effect of hypomethylation?
Increased transcription
How can abnormal methylation cause tumour growth?
1) Hypermethylation of tumour suppressor genes -> The proteins they produce to slow cell division aren’t made. This means the cells are able to divide uncontrollably.
2) Hypomethylation of proto-oncogenes -> Causes them to act as oncogenes, increasing the production of the proteins that encourage cell division. This means the cells are able to divide uncontrollably.
What is the effect of increased exposure to oestrogen?
It can increase the likelihood of some breast cancer.
What can cause increased exposure to oestrogen?
Starting menstruation earlier than usual or the menopause later than usual.
What is methylation?
Adding a methyl (-CH₃) group onto something.
How can a mutation in a tumour suppressing gene cause cancer?
- Mutations or hypermethylation causes the gene to be inactivated
- This means that the proteins required to stop cell division or cause apoptosis are no longer produced
- Cells divide uncontrollably
How does oestrogen increase the risk of breast cancer?
- It activates genes by causing the release of the inhibitor molecule from the transcription factor
- If this activates a proto-oncogene in breast tissue, this causes rapid cell division, so a tumour can form and cancerous mutations are more likely to occur
- Oestrogen concentration is further increased due to there being more cells and also due to WBCs being attracted to the area
Other research also suggests that oestrogen is able to introduce mutations directly into the DNA of certain breast cells.
What are the 2 types of risk factor for cancer?
- Genetic
* Environmental
Why is it hard to draw conclusions about the causes of cancer?
- Some characteristics are affected by multiple genes and many environmental factors
- It is difficult to tell which factors are having the greatest effect
Remember to practise looking at the graphs on pg 198 to draw conclusions about the effects of different factors on breast cancer.
See pg 198 of revision guide
How can knowing about the mutation causing a certain cancer be useful in prevention of that cancer?
The mutation can be screened for:
• If it is found, then preventative steps can be taken to prevent the cancer (e.g. mastectomy)
• More sensitive tests can be developed, which can lead to earlier and more accurate diagnosis
How can knowing about the mutation causing a certain cancer be useful in treatment and cure of that cancer?
- Treatment can be made specific to the type of cancer
- How aggressive the cancer is can determine how aggressive the treatment needs to be
- Gene therapy may be able to treat some cancers caused by some mutations
What do all cells originally come from?
Stem cells
What are stem cells?
Unspecialised cells that can develop into other types of cell.
In what two places can stem cells be naturally found?
- Embryo
* Some adult tissues
Why are there stem cells in some adult tissues?
So that old specialised cells can be replaced.
What are the different types of natural stem cell?
- Totipotent stem cells
- Pluripotent stem cells
- Multipotent stem cells
- Unipotent stem cells
What are totipotent stem cells?
- Stem cells that can divide into any type of body cell
* Only present in the first few cell divisions of an embryo
What are pluripotent stem cells?
- Stem cells that can specialise into any body cell BUT no longer have the ability to become cells that make up the placenta
- Formed from totipotent stem cells after a few embryonic divisions
What are multipotent stem cells?
- Stem cells that can divide into a few different types of cell
- These are found in adult mammals
What are unipotent stem cells?
- Stem cells that can divide into one type of cell
* These are found in adult mammals
Where is each of these found: • Totipotent stem cell • Pluripotent stem cell • Multipotent stem cell • Unipotent stem cell
- Totipotent stem cell -> Early embryo
- Pluripotent stem cell -> Late embryo
- Multipotent stem cell -> Adult mammals
- Unipotent stem cell -> Adult mammals
Explain the different types of natural stem cell.
- Totipotent stem cell -> These are found in the early embryo and can divide to form any type of body cell
- Pluripotent stem cell -> These are what totipotent stem cells become in the late embryo and they can divide to form any body cell except cells that make up the placenta
- Multipotent stem cell -> These can divide into a few different types of cell and are found in adult mammals.
- Unipotent stem cell -> These can divide into just one type of cell and are found in adult mammals.
Give an example of multipltent stem cells.
Stem cells in bone marrow that can differentiate into both red and white blood cells.
Give an example of unipotent stem cells.
Stem cells that can only divide to produce epidermal skin cells.
Describe how stem cells become specialised.
1) Conditions determine which genes are expressed.
2) The protein produced by this modify the cell -> Determine cell structure and control processes (such as the expression of more genes)
3) These changes cause the cell to be specialised, which is difficult to reverse.
Describe how RBCs become specialised.
A stem cell produces another cell in which the genes for haemoglobin production and removal of the nucleus are expressed. Many other genes are not expressed.
What are cardiomyocytes?
Heart muscle cells that make up a lot of the tissue in our hearts.
Can cardiomyocytes divide?
No
How is damage to the heart repaired?
New cardiomyocytes are produced from unipotent stem cells.
What type of stem cells are cardiomyocytes produced from?
Unipotent stem cells
How quickly are cardiomyocytes replaced by specialising unipotent stem cells?
Researchers do not agree - some say it is fast, others say it is slow.
How are stem cells already being used to treat some diseases?
Bone marrow transplants are used to treat:
• Leukaemia
• Lymphoma
• Genetic disorders (sickle-cell anaemia and severe combined immunodeficiency)
How could stem cells be used to treat some diseases in the future?
Stem cell treatments could work for: • Spinal cord injuries • Heart disease and damage caused by heart attacks • Bladder conditions • Respiratory diseases • Organ transplants
What are the benefits of using stem cells in medicine?
- They could save many lives
* They could improve the quality of life for many people
What are the 3 main sources of human stem cells?
1) Adult stem cells
2) Embryonic stem cells
3) Induced pluripotent stem cells
How can adult stem cells be obtained?
A relatively simple operation.
How flexible are adult stem cells?
Multipotent - so they can specialise into a limited range of cells. This is not as flexible as embryonic stem cells.
How are embryonic stem cells obtained?
- Embryos are created in a laboratory using in vitro fertilisation
- When the embryos are 4 to 5 days old, stem cells are removed from them
- The rest of the embryo is destroyed
How flexible are embryonic stem cells?
Pluripotent - so they can divide into all types of body cell (except placenta cells)
What is the shorthand for induced pluripotent stem cells?
iPS cells
How are induced pluripotent stem cells obtained?
- Adult body cells are made to express a series of transcription factors that are normally associated with pluripotent stem cells
- This can be done by infecting the cells with a modified virus that has genes coding for the transcription factor within its DNA.
- These genes are passed into the adult cell’s DNA, so the cell can produce the transcription factors.
- This causes genes that are associated with pluripotency to be expressed.
When producing induced pluripotent stem cells, how are the adult stem cells made to express the transcription factors that are associated with pluripotent stem cells?
- The cells are infected with a modified virus that has genes coding for the transcription factor within its DNA.
- These genes are passed into the adult cell’s DNA, so the cell can produce the transcription factors.
Remember to practise writing out how iPS cells are produced.
Pg 202 of revision guide
Why might induced pluripotent stem cells be useful in research and medicine?
- They might be able to replace embryonic stem cells (in terms of flexibility), which have ethical issues.
- They could be made from the patient’s own cells, which reduces the risk of rejection.
What are some of the different ideas people have about embryonic stem cells?
- Some people believe that at the moment of fertilisation an individual is formed with the right to life.
- Some people believe have fewer objections if the stem cells are obtained from egg cells that haven’t been fertilised by sperm, but have been artificially activated to start dividing. This is because a fetus wouldn’t be produced if this was placed in a womb.
What are some ethical issues surrounding embryonic stem cell use?
Obtaining them results in the destruction of an embryo that could become a fetus if placed in a womb.
What is transcription?
When a gene is copied from DNA into mRNA>
What enzyme is responsible for synthesising mRNA?
RNA polymerase
Why does the structure and function of different cells in an organism vary?
- Not all of the genes are expressed.
* So different proteins are made and these proteins modify the cell.
What are transcription factors?
Chemicals that control the transcription of target genes.
What are the two types of transcription factor?
- Activators
* Repressors
Where do transcription factors move from and to?
From the cytoplasm to the DNA in the nucleus.
Describe how transcription factors work.
1) Transcription factors move from the cytoplasm to the nucleus.
2) In the nucleus, they bind to specific DNA sites near the start of the target gene.
3) Some transcription factors, called activators, stimulate transcription (e.g. by helping RNA polymerase bind)
4) Other transcription factors, called repressors, inhibit or decrease the rate of transcription (e.g. by preventing RNA polymerase from binding)
(See diagram pg 204 of revision guide)
What type of chemical is oestrogen?
Steroid hormone
What is the role of oestrogen?
It initiates the transcription of target genes.
When does oestrogen move from and to?
From the cytoplasm to the DNA in the nucleus.
Describe how oestrogen works.
1) In the cytoplasm, oestrogen combines with an oestrogen receptor, forming an oestrogen-oestrogen receptor complex.
2) The complex moves from the cytoplasm into the nucleus where it binds to specific DNA sites near the start of the target gene.
3) The complex acts as an activator of transcription (e.g. by helping RNA polymerase bind).
(See diagram pg 204 of revision guide)
Does an oestrogen-oestrogen receptor complex always act as an activator?
No, in some cells it can act as a repressor (but the spec doesn’t mention this).
What is RNA interference?
When small double-stranded RNA molecules stop mRNA being translated into proteins.
What is shorthand for RNA interference?
RNAi
What are the molecules involved in RNAi called?
- siRNA
* miRNA
What does siRNA stand for?
Small interfering RNA
What does miRNA stand for?
MicroRNA
What are RNAi molecules?
Small lengths of non-coding RNA.
In what types of organisms does RNAi occur?
Eukaryotes and some prokaryotes
How does siRNA work?
1) Once mRNA has been transcribed, it leaves the nucleus for the cytoplasm.
2) In the cytoplasm, double-stranded siRNA associates with several proteins and unwinds.
3) A single strand then binds to the target mRNA due to a complementary base sequence.
4) The proteins attached to the siRNA cut the mRNA into the fragments, so it cannot be translated.
5) These parts now move into a processing body where they’re degraded.
6) A similar process happens with miRNA in plants.
(See diagram pg 205 of revision guide)
Where does RNAi using miRNA work?
- In mammals
* In plants (but the process is like with siRNA)
How does miRNA work?
1) Once mRNA has been transcribed, it leaves the nucleus for the cytoplasm.
2) In the cytoplasm, double-stranded miRNA associates with several proteins and unwinds.
3) A single strand then binds to the target mRNA. However, the strand is only near-complementary, so it can target more than one mRNA molecule.
4) The miRNA-protein complex physically blocks the translation of the target mRNA.
5) These parts now move into a processing body where they’re degraded or stored.
6) If they’re stored, they can be returned and translated another time.
(See diagram pg 205 of revision guide)
What is the difference between how siRNA and miRNA work?
- siRNA -> Is complementary to the mRNA, so the proteins cut the mRNA into fragments
- miRNA -> Is only near-complementary, so the miRNA-protein complex just physically prevents translation from occurring.
What are the different ways in which transcription and translation can be regulated?
- Transcription -> Transcription factors and oestrogen
* Translation -> siRNA and miRNA
Remember to practise interpreting the experimental data on transcription and translation regulation on pg 206 of revision guide.
Do it.
What is epigenetic control?
The switching on or off of a gene by attaching or removing chemical groups on the DNA or histone proteins.
How does epigenetic control work?
- Chemical groups are attached to or removed from the DNA and histones
- This alters how easy it is for the enzymes and other proteins needed for transcription to interact with and transcribe the DNA
Does epigenetic control alter the base sequence of DNA?
No
Can epigenetic changes be inherited?
Some of them are.
What are the two types of epigenetic control you need to know about?
1) Methylation of genes
2) Acetylation of histones
What is the effect of methylation of DNA?
Increased methylation switches a gene off.
What is methylation of DNA and where does it occur?
- A methyl group is attached to the DNA coding for a gene
- This is always a a CpG site (which is where a cytosine and guanine base are next to each other in the DNA - linked by a phosphodiester bond)
Describe how methylation causes changes in gene expression.
- A methyl group is attached to the DNA coding for a gene
- This changes the DNA structure so that it is more difficult for transcriptional machinery (enzymes, proteins, etc.) to interact with the gene
- So the gene is switched off
What is the effect of acetylation of histones?
Increased acetylation turns a gene off.
What is acetylation of a histone?
When an acetyl group is added to a histone.
Describe how acetylation causes changes in gene expression.
- An acetyl group is added to a histone
- This causes the DNA to be wrapped less tightly around the histone
- This means the transcriptional machinery (enzymes, proteins, etc.) can access the DNA more easily
- So the gene is switched on
What is chromatin?
The combination of DNA wrapping around histones.
NOTE: Check this
What enzyme is responsible for removing acetyl groups in decreased acetylation of histones?
Histone deacetylase (HDAC)
What is the role of epigenetics in disease?
Epigenetics can contribute to many diseases, so it can be targeted in treatment.
Describe how epigenetics can contribute to the development of Fragile-X syndrome.
1) Fragile-X syndrome is a genetic disorder that can cause symptoms such as learning and behavioural difficulties, as well as characteristic physical features
2) It’s caused by the heritable duplication mutation on the X chromosome, called FMR1. The mutation results in the short DNA sequence CGG being repeated many more times than usual.
3) These repeats mean that are many more CpG sites in the gene than usual, so there is increased methylation of DNA, switching the gene off.
4) The protein coded for by the gene isn’t produced, so the symptoms of the disease occur.
How can drugs be used to treat diseases caused by epigenetic changes?
Drugs are used to target epigenetic changes that cause diseases.
Remember to revise how drugs can target epigenetic changes.
Pg 208 of revision guide
What is the problem with developing drugs to counteract epigenetic changes?
These changes take place normally in a lot of cells, so it’s important to make sure the drugs are as specific as possible (e.g. drugs in cancer therapy can be designed only to target dividing cells to avoid damaging normal body cells).
How can drugs be used to target methylation of DNA in order to treat diseases?
Drugs that stop DNA methylation can be used to be treat diseases caused by increased methylation that turns off genes.
How can drugs be used to target acetylation of histones in order to treat diseases?
HDAC inhibitor drugs can be used to treat diseases that are caused by decreased acetylation that switches off genes.
What two factors influence phenotype?
- Genotype
* Environment
Describe how theories about the causes of overeating changed over time.
- It was thought that overeating was caused only by environmental factors, like an abundance of food
- It was later found that dopamine levels in animals increase when eating, and people would stop eating once enough dopamine was released
- But researchers discovered that people with a certain allele had 30% fewer dopamine receptors, making them more likely to overeat
- So it was shown that overeating has both genetic and environmental causes
Describe how theories about the causes of antioxidant levels in berries changed over time.
- Scientists thought that differences in antioxidant levels between species of berry depended only on genetic factors
- However, experiments showed that environmental conditions caused a lot of variation
- So it was shown that antioxidant levels in berries depends on both genetic and environmental causes
Is it easy to determine whether genetic or environmental causes have more of an effect on a phenotype?
No
How can you determine whether genetic or environmental causes have more of an effect on a phenotype?
Twin studies
How can twin studies help determine whether genetic or environmental causes have more of an effect on a phenotype?
- Identical twins are genetically identical, so any differences between their phenotypes must be entirely due to environmental factors.
- If a characteristic is very similar in identical twins, genetics probably plays a more important role.
- If a characteristic is different between the twins, the environment must have a larger influence.
