Topic 8A: Mutations and Gene Expression Flashcards
Definition: Mutation
A change in the base sequence of DNA.
What are the different types of mutation?
- Substitution
- Deletion
- Addition
- Duplication
- Inversion - a sequence of bases is reversed.
- Translocation - a sequence of bases is moved from one location in the genome to another
What are the affects of mutations?
1) Base sequence of DNA is changed.
2) The sequence of amino acids in the polypeptide could be changed.
3) The tertiary structure of the protein is changed.
4) Unable to function properly.
What are hereditary mutations?
When a gamete containing a mutation is fertilised, meaning the mutation is present when the foetus forms. Therefore, they are passed on to the offspring.
Why are not all mutations harmful?
1) The degenerate nature of the genetic code means some amino acids are coded for by more than one DNA triplet.
2) Therefore, not all types of mutation will cause a change in the amino acid sequence of a polypeptide.
What are frameshift mutations?
1) Addition, duplication or deletion occurs meaning there is a change in the number of bases in the DNA code.
2) Therefore, there is a shift in the base triplets that follow, so the triplet code is read in a different way.
3) This means you get a completely amino acid sequence.
Definition: Mutagenic agents
Something which increases the rate of mutations by:
• Acting as a base.
• Altering bases.
• Changing the structure of DNA.
Definition: Acquired mutations
Mutations that occur after fertilisation.
Formation of tumours: Mutations in tumour suppressor genes
1) When functioning normally, tumour suppressor genes slow down cell division by producing proteins which stop cells dividing and cause them to self-destruct in a process called apoptosis.
2) If a mutation occurs, the gene will becomes inactive, meaning the protein it codes for isn’t produced.
3) Therefore cells divide uncontrollably, resulting in a tumour.
Formation of tumours: Mutations in proto-oncogenes
1) When functioning normally proto-oncogenes stimulate cell division by producing proteins which make cells divide.
2) If a mutation occurs, the gene becomes overactive, stimulating the cells to divide uncontrollably, resulting in a tumour.
What is an oncogene?
A mutated proto-oncogene.
Tumours: Malignant tumours
- Cancerous tumours which grow rapidly and invade and destroy surrounding tissues.
- Cells can break off the tumour and spread to other parts of the body in the bloodstream or lymphatic system.
Tumours: Benign tumours
- Non-cancerous tumours which grow slower and contain fibrous tissue preventing them from invading other tissues.
- Often harmless, but can cause blockages or put pressure on organs.
Features of tumour cells
- Large, dark nucleus.
- Irregular shape.
- Different surface antigens.
- Don’t respond to growth regulating processes.
- Divide by mitosis more frequently.
Growth of tumours: Abnormal methylation of tumour suppressor genes
1) If tumour suppressor genes are hyper-methylated the proteins they produce to slow cell division aren’t made.
2) Therefore, the cells divide uncontrollably by mitosis and a tumour develops.
Growth of tumours: Abnormal methylation of proto-oncogenes
1) If proto-oncogenes are hyper-methylated they act as oncogenes, causing increased production of the protein that causes cell division.
2) Therefore, the cells divide uncontrollably by mitosis and a tumour develops.
Growth of tumours: Oestrogen
1) Oestrogen stimulates breast cells to divide and replicate, meaning the more oestrogen you have, the higher the rate of cell division and so the chances of a mutation occurring are increased.
2) Also, if cells do become cancerous, their rapid replication could be further assisted by oestrogen, helping tumours to grow quickly.
Definition: Stem cell
An unspecialised cell which has the ability to develop into other types of cell.
Stem cells: Totipotent
Totipotent stem cells are stem cells which are able to develop into any type of body cell.
Stem cells: Pluripotent
Pluripotent stem cells are stem cells which are able to develop into any type of body cell, apart from placental cells.
Stem cells: Multipotent
Multipotent stem cells are only able to divide into a few different types of cell.
Stem cells: Unipotent
Unipotent stem cells are only able to develop into one type of cell.
How do stem cells become specialised?
1) Stem cells become specialised because during their development they only transcribe and translate part of their DNA.
2) This means only certain genes are expressed and the others are switched off.
3) Expressed genes get transcribed into mRNA which is then translated into proteins which modify the cell.
4) This causes the cell to become specialised.
What are cardiomyocytes?
Heart muscle cells which can only be replaced (if damaged) by new cardiomyocytes derived from a small store of unipotent stem cells in the heart.
Existing stem cell therapies: Bone marrow transplants
- Bone marrow contains stem cells that can become specialised to form any type of blood cell, meaning bone marrow transplants can be used to replace faulty bone marrow in patients that produce abnormal blood cells.
- The stem cells in the transplanted bone marrow divide and specialise to produce healthy blood cells.
Future stem cell therapies
- Stem cells could be used to replace damaged nerve tissue.
- Stem cells could be used to replace damaged heart tissue.
- Stem cells could be used to grow whole bladders which are used to replace diseased ones.
- Stem cells can be used to grow whole organs.
Sources of stem cells: Adult stem cells
• Obtained from the body tissue of an adult.
✔️ Relatively easy to obtain with little risk, only discomfort.
✖️ Only able to specialise into a limited range of cells.
Sources of stem cells: Embryonic stem cells
• Obtained from embryos at an early stage of development.
✔️ Can divide an unlimited number of times and develop into all types of body cell.
✖️ Embryos are destroyed - right to life?
Sources of stem cells: Induced pluripotent stem cells
• Created by scientists in a lab by reprogramming adult body cells to become pluripotent.
✔️ Can divide an unlimited number of times and develop into all types of body cell.
✖️ More research needed before they are properly used.
Why is transcription controlled?
To determine which genes are expressed, and which are not, to allow proteins to carry out their specific functions.
Function: Transcription factors
They bind to promoter regions near the start of target genes, and control expression by controlling the rate of transcription.
Transcription factors: Activators
Stimulate or increase the rate of transcription by helping RNA polymerase to bind to the start of gene and activate transcription.
Transcription factors: Repressors
Inhibit or decrease the rate of transcription by binding to the start of the target gene, preventing RNA polymerase from binding, stopping transcription.
Factors affecting gene expression (transcription): Oestrogen
1) Oestrogen binds to an oestrogen receptor to form an oestrogen-oestrogen receptor complex.
2) This moves from the cytoplasm into the nucleus, where it binds to specific DNA sites near the start of the target gene.
3) This helps RNA polymerase to bind to the start of the target gene, causing the gene to be expressed.
Factors affecting gene expression (translation): siRNA
1) Once mRNA has been transcribed it leaves the nucleus and enters the cytoplasm.
2) Here, double-stranded siRNA associates with several proteins and unwinds.
3) One of the resulting single strands of siRNA is broken down and the other is selected.
4) The single strand of siRNA then binds to the target mRNA, through complementary base pairing.
5) The proteins associated with the siRNA cut the mRNA into fragments, so that it can no longer be translated, and is instead degraded.
6) Therefore, the gene isn’t expressed.
Definition: Gene expression
When a gene is transcribed and used to make a protein.
Factors affecting gene expression (translation): miRNA
1) Once miRNA has been transcribed it leaves the nucleus and enters the cytoplasm, as a long folded double strand.
2) Here, it associates with several proteins and unwinds.
3) One of the resulting single strands of miRNA is broken down and the other is selected.
4) The single strand of miRNA then binds to the target mRNA, meaning the target mRNA isn’t translated.
5) The mRNA is then degraded and the gene isn’t expressed.
What is epigenetic control?
The attachment or removal of chemical groups (called epigenetic marks) to or from DNA/Histone proteins to determine whether or not a gene is expressed.
How do epigenetic marks work?
They alter how easy it is for the enzymes and other proteins needed for transcription to interact with and transcribe DNA.
Controlling gene expression: Increased methylation of DNA
1) Methyl group is attached to the DNA.
2) This changes the DNA structure so that transcriptional machinery (such as enzymes) cannot interact with the gene meaning it is not expressed.
Controlling gene expression: Decreased acetylation of histones
1) By adding an acetyl group, the chromatin is less condensed, allowing the transcriptional machinery to access the DNA, allowing genes to be transcribed.
2) By removing an acetyl group, the chromatin becomes more condensed, meaning the transcriptional machinery is unable to access the DNA, and therefore the genes cannot be transcribed.
