Topic 8A - Mutations and Gene Expression Flashcards
Define mutation
A mutation is any change to a base sequence of DNA, caused by errors during DNA replication
Define the 6 different types of mutations.
(SADDIT)
- Substitution: when 1+ bases are swapped for another.
- Addition: 1+ bases are added
- Deletion: 1+ bases are removed
- Duplication: 1+ bases are repeated
- Inversion: A sequence of bases is reversed.
- Translocation: A sequence of bases is moved from one location in genome to another. This could be movement within same chromosome or movement to a different chromosome.
Why can mutations affect proteins/characteristics?
The order of DNA sequences determine the order of amino acids in a polypeptide, which determines shape of a protein
- If there is a mutation, order of amino acid may change, which could change the shape of the protein, so it no longer works. (e.g. enzyme active site would change, so substrate will no longer be able to fit into it, and it is denatured)
What type of things can mutations lead to?
give 3 points and some examples
- Genetic disorders e.g. cystic fibrosis
- Increased likelihood of developing cancer e.g mutations on the gene BRCA1 can increase the chances of developing breast cancer.
What are hereditary mutations?
They are mutations that will be present in a fetus when a gamete, containing a mutation for a genetic disorder/type of cancer, is fertilised.
Are all hereditary mutations harmful?
No, some drive evolution
Do all mutations affect the order of amino acids?
No as the degenerate nature of the genetic code means that some amino acids are coded for by more than one triplet code. This means that not all mutations will result in a different amino acid sequence
- THESE ARE CALLED SILENT MUTATIONS
What 2 types of mutations may not lead to a change in amino acid sequence?
look at examples on page 194
- (SOME) Substitution
2. (SOME) Inversion
What type of mutations lead to a change in amino acid sequence and why?
look at examples on page 195
- Additions
- Duplications
- Deletions
As they change the number of bases in the DNA code.
- This causes a shift (called a frameshift) in the base triplets that follow, so that the triplet code is read in a different way
Do mutations occur randomly or systematically?
Randomly
What are mutagenic agents (and give examples of some)
Mutagenic agents are things that increase the rate of mutations e.g. ultraviolet radiation, ionising radiation, some chemicals and some viruses
How do mutagenic agents increase the rate of mutations?
- Acting as a base
- Altering bases
- Changing the structure of DNA
How does the ‘acting as a base’ increase the rate of mutation?
Acting as a base - Chemicals called base analogs can substitute for a base during DNA replication, changing the base sequence in the new DNA (E.g. 5-bromouracil is a base analog that can substitute for thymine, it can pair with guanine (instead of adenine), causing a substitution mutation in the new DNA
How does ‘altering bases’ increase the rate of mutations?
Altering bases - some chemicals can delete or alter bases (e.g. alkylating agents can add an alkyl group to guanine, which changes the structure so that it pairs to thymine instead of cytosine.
How does ‘changing the structure of DNA’ increase the rate of mutations?
Changing the structure of DNA - Some types of radiation can change the structure of DNA, which causes problems during DNA replication. (e.g. UV radiation can cause adjacent thymine bases to pair up together)
What are acquired mutations?
They are mutations that occur in the individual cells after fertilisation
What can happen if acquired mutations occur in genes that control the rate of cell division?
It can cause UNCONTROLLED cell division, which can form a tumour. Tumours can invade and destroy surrounding tissues, and turn into cancers.
What is a tumour?
A mass of abnormal cells
Name the 2 types of genes that control cell division
- Tumour suppressor genes
2. proto-oncogenes
What effect do mutations have on tumour suppressor genes?
Tumour suppressor genes can be inactivated if a mutation occurs in the DNA sequence
- when dividing normally, tumour suppressor genes slow cell division by producing proteins that stop cells dividing or cause them to self-destruct (apoptosis)
- If a mutation occurs in tumour suppressor gene, the protein isn’t produced. The cells divide uncontrollably, resulting in a tumour —-> cancer
What effect do mutations have on proto-oncogene?
The effect of a proto-oncogene can be increased if a mutation occurs in a DNA sequence. A mutated proto-oncogene is called an oncogene.
- When functioning normally, proto-oncogenes stimulate cell division by producing proteins that make cells divide
- If mutation occurs in proto-oncogene, gene can become overactive and produce more proteins, so that cells divide uncontrollably and result in a tumour –> cancer
Name the two different types of tumours.
Benign and malignant tumours
What are benign tumours?
Non-cancerous tumours.
- they grow slower than malignant tumours and are often covered in fibrous tissue to stop cells invading other tissues. They are often harmless, but they can cause blockages and put pressure on organs
- some benign tumours can become malignant
What are malignant tumours?
Cancerous tumours
- They grow rapidly and invade and destroy surrounding tissues. Cells can break off the tumours and spread to other parts of the body in the bloodstream or lymphatic system
How are tumour cells different to normal cells?
6 points
- They have an irregular shape
- The nucleus is larger and darker than in most cells (sometimes the cells have more than one nucleus)
- They don’t produce all proteins needed to function correctly
- They have different antigens on their surface
- They don’t respond to growth regulating processes.
- They divide, by mitosis, more frequently than normal cells
What is ‘methylation of DNA’??
adding a methyl group (CH3) group onto DNA
Why is methylation of DNA important ?
It helps regulate gene expression - it can control whether or not a gene is transcribed (copied into mRNA) and translated (turned into a protein)
When does methylation of DNA become a problem?
It becomes a problem when it happens too much (hypermethylation) or too little (hypomethylation)
Give an example of the effect of hypermethylation
When tumour suppressor genes are hypermethylated, the genes are not transcribed - so the proteins they produce to slow cell division aren’t made. This causes cells to divide uncontrollably, so that tumours develop.
Give an example of the effect of hypomethylation
Hypomethylation of proto-oncogenes causes them to act as oncogenes, which makes the gene overactive, so that more proteins are made, and more cells start to divide uncontrollably, which causes tumours to develop.
What can contribute to breast cancer?
Increased exposure to Oestrogen e.g. through starting menopause earlier/later than usual, or through oestrogen containing drugs e.g. HRT.
Give 2 theories as to why ………….. can contribute to breast cancer.
- Oestrogen can stimulate certain breast cells to divide and replicate. The fact that more cell divisions are taking place naturally increases the chances of mutations occurring, and so increases the chance of cells becoming cancerous.
- This ability to stimulate division can mean that if cells become cancerous, their rapid replication could be further assisted by oestrogen, helping tumours to form quickly ** - Other research suggests that oestrogen is able to introduce mutations directly into DNA of certain breast cells, increasing chances of these cells becoming cancerous.
What 2 types of factors affect the risk of cancer?
give examples
- Genetic factors e.g. some cancers are linked with specific inherited alleles. If you inherit that allele you’re more likely to get that type of cancer)
- Environmental factor e.g. exposure to radiation, lifestyle choices such as smoking, increased alcohol consumption, and a high-fat diet have been linked to an increased chance of developing cancer.
Why is it hard to draw conclusions about the causes of variation on data/graphs?
hint
- genes
- environment
It is difficult as some characteristics can be affected by many different genes (polygenic) and many environmental factors.
- It’s difficult to know which factor (genes or environment) has the greatest effect
Look at questions on interpreting data on variation
page 198
What causes cancer?
Mutations in proto-oncogenes and tumour suppressor genes
Describe how knowing about mutations can help PREVENT cancer.
If specific cancer-causing mutation is known, then we can screen for mutation in someone’s DNA (e.g. we can screen for mutated allele of BRCA1 tumour suppressor gene)
- This means we can take preventative steps to reduce risk e.g. woman with BCR1 mutation can choose to have a masectomy. They may also be screened more often than others as early diagnosis increases chance of recovery
Describe how knowing about mutations can help TREAT AND CURE cancer
- Knowing how specific mutations cause cancer allows us to make drugs/therapy to target them (e.g. Herceptin is used to combat HER2 proto-oncogene mutation and high doses of radiotherapy can be used to treat aggressive cancers)
- Gene therapy = allows us to replace faulty alleles in person’s cell with working versions of those alleles. e.g. if you know cancer is caused by mutated tumour suppressor genes, gene therapy can be used to provide working versions of the genes
What are stem cells?
Stem cells are unspecialised cells that divide to become new cells, which then become specialised cells.
Do all multicellular organisms have some form of stem cell or only some?
All
Where are stem cells found?
- Some in embryo (where they become specialised cells needed to form a fetus)
- Some in adult tissues (where they become specialised cells that need to be replaced e.g. stem cells in the intestines constantly replace intestinal epithelial cells)
What are totipotent cells?
Stem cells that can mature into any type of body cell in an organism (including placenta cells).
- These are only present in mammals in the first few cell divisions of an embryo
What are pluripotent cells?
After the first few divisions of an embryo, cells no longer are totipotent, they become pluripotent. Plurpotent cells can specialise into any body cells except placenta cells.
Name the 2 types of stem cells present in adult stem cells?
- Multipotent cells
2. Unipotent cells
What are multipotent cells?
They are cells that can differentiate into a few different types of cell e.g. both red and white blood cells
What are unipotent cells?
Cells that can only differentiate into 1 type of cell e.g. the cell that can only divide to produce epidermal skin cells, which make up the upper layer of our skin.
Describe, in terms of transcription and translation, how stem cells become specialised.
- In stem cells, only some genes are transcribed and translated. Therefore, mRNA for specific genes is transcribed but not all
- The mRNA from these genes is translated into proteins so that some genes are expressed.
- These proteins determine the cell structure and control cell processes including the expression of more genes, which produces more proteins).
- Changes to the cell produced by the proteins cause the cell to become specialised. These changes are difficult to reverse, so once a cell is specialised, it stays specialised.
Describe how red blood cells became specialised?
Red blood cells are produced by a type of stem cell in bone marrow. They contain lots of haemoglobin and no nucleus (to make room for more heamoglobin)
- The stem cell produces a new cell in which the genes for hemoglobin production are expressed. Other genes, such as those involved in removing the nucleus are also expressed. Many other genes are not expressed (switched off), resulting in a specialised red blood cell.
What are cardiomyocytes?
Heart cells that make up a lot of tissue in our hearts
What can’t heart cells do?
It is thought that they can’t divide to replicate themselves?
What assumption did people have about heart cells?
People assumed that, as heart cells can’t divide to replicate themselves, we weren’t able to regenerate our own heart cells. This is a problem if the heart becomes damaged e.g. by a heart attack, or the cells become worn out with age.
How was the argument that ‘we can’t regenerate our own heart cells’ refuted?
Some scientists believe that heart does have regenerative capability. They now think that old or damaged cardiomyocytes can be replaced by new cardiomyocytes derived from a small supply of unipotent stem cells in heart.
- They believe this process is constantly occurring but haven’t agreed on how it quickly it happens. Some say its a slow process and some cardiomyocytes are never replaced throughout a lifetime. Others believe it occurs more quickly, so that every cardiomyocyte is replaced several times throughout a lifetime.
Describe some stem cell therapies that exist?
BONE MARROW TRANSPLANTS
- Bone marrow transplants can be used to replace faulty bone marrow in patients that produce abnormal body cells. The stem cells in transplanted bone marrow divide and specialise to produce healthy blood cells.
- This technique has been used to successfully leukaemia (a cancer of the blood or bone marrow) and lymphoma (a cancer of the lymphatic system). It has also been used to treat sickle-cell anaemia and severe combined immunodeficiency (SCID)
Give an example of how a bone marrow transplant can be used to treat a disease?
Bone marrow transplants for SCID
SCID patients produce white blood cells that are defective so they can’t defend their body against diseases. Bone marrow transplants introduce new stem cells to a person, which can divide to reproduce non-faulty white blood cells
Describe how stem cells may be used to treat other diseases, IN THE FUTURE?
Hint:
- SHBRO
1- Spinal cord injuries: can be used to replace damaged nerve tissues
2- Heart disease and damage caused by heart attacks: can be used to replace damaged heart tissue.
3- Bladder conditions: Can be used to grow whole bladders, which are then implanted in patients to replace diseased ones.
4- Respiratory diseases: Donated windpipes can be stripped down to their simple collagen structure and then covered with tissue generated by stem cells. This can then be transplanted into patients.
5- Organ transplants: Organs can be grown from stem cells to provide new organs for people on donor waiting lists.
What are the 3 main potential sources of human stem cells?
- Adult stem cells
- Embryonic stem cells
- Induced pluripotent stem cells (iPS Cells)
What are adult stem cells?
(in your answer, include:
- how they can be obtained?
- a main difference between these cells and embryonic stem cells
They are stem cells that can be obtained from the bone marrow of an adult, in a relatively simple operation with very little risk involved, but quite a lot of discomfort.
- They are multipotent so they aren’t as flexible as embryonic stem cells/they can only specialise into a limited range of cells
What are embryonic stem cells?
(in your answer, include:
- How they can be obtained?
- a main difference between these and adult stem cells
These are stem cells obtained from embryos that are created in a lab using IVF. Once the embryos are approximately 4-5 days old, stem cells are removed from them and the rest of the embryo is destroyed/
- They are pluripotent so they can divide an unlimited number of times and develop into any type of body cell.
What are iPS cells?
In your answer, include:
- How they can be created?
Adult specialised cells are made to express a series of transcription factors that are normally associated with pluripotent stem cells.
- This is done by injecting adult cells with a specially-modified virus. Virus has genes coding for the transcription factors within its DNA. When virus injects the adult cell, these genes are passed into adult’s cell’s DNA, meaning that the cell is able to produce the transcription factors.
- The transcription factors cause adult cells to express genes that are associated with pluripotency.
Give an argument FOR and AGAINST the use of stem cells?
AGAINST: Raises ethical issues as procedure involved destroying an embryo that could become a human life if placed in the womb
FOR:
- We can use certain stem cells that haven’t been fertilised by sperm but have only been artifically activated to divide as they wouldn’t survive past a few days anyway, and wouldn’t produce a fetus if placed in the womb.
- We can use induced pluripotent stem cells
What are the advantages of using iPS cells?
give 2
- They have the potential to be as flexible as embryonic stem cells but come from adult tissue so less ethical issues
- It’s also possible that iPS cells can be made from a patients own cells. These iPS cells would be genetically identical to the patient’s cell and can be used to grow a new tissue/organ that the body wont reject.
Why do the structure and function of cells vary, even though they carry the same genes?
They vary as not all the genes in a cell are expressed (transcribed and used to make a protein)
- because different genes are expressed, different proteins are made and these proteins modify the cell - they determine the cell structure and control cell processes (including the expression of more genes, which produce more proteins).
What are transcription factors?
Proteins that control the rate of transcription in genes
How do transcription factors work?
- In eukaryotes, they move from cytoplasm to nucleus
- In nucleus, they bind to specific DNA sites near start of target genes (the genes they control expression of)
- They control expression by controlling the rate of transcription
What are activators and what do they do?
give example of what they do
They are transcription factors and they stimulate/increase the rate of transcription. e.g. they help RNA polymerase bind to start of target gene and activate transcription
What are repressors and what do they do?
They are transcription factors and they decrease the rate of transcription e.g. they bind to the start of the target gene, preventing RNA polymerase from binding, stopping transcription.
What factor can initiate the transcription of target genes?
Oestrogen
What is Oestrogen and how does it affect gene expression?
- Oestrogen is a steroid muscle and it can affect transcription by binding to transcription factor called an oestrogen receptor, forming an O-O receptor complex
- Complex moves from cytoplasm to nucleus and binds to specific DNA sites near start of target gene, causing it change shape (helping RNA polymerase to bind to it)
- O-O complex can sometimes act as a repressor but it depends on the type of cell and the target gene.
What is RNA interference (RNAi)?
It is the process in which small double-stranded RNA molecules stop mRNA being translated into proteins.
What 2 molecules are involved in RNAi?
- siRNA (small interfering RNA)
2. miRNA (microRNA)
What does siRNA work (and miRNA in plants)?
- Once mRNA has been transcribed, it leaves nucleus for cytoplasm.
- In cytoplasm, double stranded siRNA associates with many proteins and unwinds. A single strand then binds to target mRNA by complementary base pairing.
- Enzymes associated with siRNA cut the mRNA into fragments - so it can no longer be translated. The fragments then move into a processing body, which contains ‘tools’ to degrade them.
(similar process happens in plants with miRNA)
How does miRNA work (in mammals)?
- In mammals, miRNA isn’t fully complementary to target mRNA. This makes it less specific than siRNA and so it may target more than 1 mRNA molecule.
- Like siRNA, it associates with proteins and binds to target mRNA in cytoplasm.
- miRNA-protein complex physically blocks the translation of target mRNA (instead of enzymes doing the cutting)
- The mRNA is then moved into a processing body, where it can either be stored or degraded. When it’s stored, it can be returned and translated at another time/
Do questions on interpreting experimental data on gene expression
Page 206
What are the 4 ways of controlling gene expression?
- Transcription factors
- Oestrogen
- RNAi interference (RNAi)
- Epigenetic control
Generally outline how does epigenetic control work?
It works by attaching/removing chemical groups (knows as epigenetic marks) to or from DNA and histone proteins.
- These marks dont alter the base sequence of DNA but they alter how easy it is for enzymes and other proteins needed for transcription to interact with and transcribe the DNA.
When can epigenetic changes play a role?
They can play a role in lots of normal celullar processes and can also occur in response to changes in the environment e.g. pollution
What happens to most epigenetic marks on DNA between generations?
Most of them are removed (but some are passed on to offspring - this means that expression of some genes in offspring can be affected by environmental changes that affected their parents/grandparents. )
Outline 2 methods of epigenetic control?
- Increased methylation of DNA
2. Decreased acetylation of histones
Describe how (increased) methylation of DNA can control gene expression.
(LOOK UP DIAGRAM OF THIS PROCESS)
- A methyl group (CH3) attaches to a DNA coding for a gene
- The group always attaches to a CpG site, where a cytosine and guanine base are next to each other. (linked by a phosphodiester bond)
- Increased methylation changes the DNA structure so that enzymes/proteins can’t interact with the gene - so the gene is not expressed/switches off
What is chromatin?
The histone wrapped around the DNA
Describe how (decreased) acetylation of histones can control gene expression
Histones can be genetically modified by adding/removing acetyl groups (an epigenetic mark)
- When histones are acetylated, chromatin is less condensed so enzymes/proteins can access DNA and transcribe genes
- When acetyl groups are removed from histones, chromatin is more condensed so enzymes/proteins can’t access it and transcribe genes in DNA.
What enzyme is responsible for removing acetyl groups?
Histone deacetylase
Name a disease caused by epigenetics (other than cancer)
Fragile X syndrome
What is fragile X syndrome and describe what causes it?
A genetic disorder that leads to symptoms like learning/behavioural difficulties and characteristic physical features.
It is caused by a heritable mutation in a gene on the X chromosome, called FMR1. The mutation results in the short DNA sequence CGG being repeated many more times than usual.
- These repeats mean there are lots more CpG sites in gene than usual. More CpG sites result in increased methylation of gene, which switches it off. As gene is switches off, protein isn’t produced, which causes the symptoms of the disease.
Are epigenetic changes reversible?
Yes
Why is it good that epigenetic changes are reversible?
It means that we can develop drugs to combat diseases caused by epigenetic changes e.g. drugs that prevent increased methylation of DNA and decreased acetylation of histones.
Give an example of a drug used to prevent increased methylation of DNA?
Azacitidine
- it works by stopping DNA methylation and is used in chemotherapy for types of cancer caused by increased methylation of tumour suppressor genes.
Give an example of a drug used to prevent decreased acetylation of histones
Histone deacetylase (HDAC) inhibitor drugs e.g. romidepsin - These work by inhibiting the activity of HDAC enzymes responsible for removing the acetyl groups from the histones. Without the activity of HDAC enzymes, the genes remain acetylated and the proteins they code can be transcribed.
What must scientists take into account when developing drugs to target epigenetic changes?
The drugs must be specific to cancer cells, so that they dont damage other bodily cells that are functioning normally
Evaluate data about influences on phenotypes
page 209
What can be used to determine whether influences on phenotypes are genetic or environmental?
Twin studies.
