Gene Expression Flashcards
Mutations and types of mutations?
Mutations are any chance to the base (nucleotide) sequence of DNA.
They can be caused by errors during DNA replication and can be increased by mutagenic agents.
Types:
- Substitution,
- Deletion,
- Addition,
- Duplication,
- Inversion,
- Translocation.
Inversion Of Bases?
This mutation occurs on the DNA base sequence but changes the entire chromosome.
What Happens:
- A group of bases become separated from the DNA sequence
Substitution?
One or more bases are swapped for another.
ATG > ATC
Deletion?
One or more bases are removed.
ATG > AT
This can cause a frame shift.
Addition?
One or more bases are added.
ATG > ATGA
Duplication?
One or more bases are repeated.
ATG > ATGG
This is different to addition because G is being repeated rather than another random base being added. This is kind of a type of addition though.
Inversion?
A sequence of bases is revered.
ATG > GTA
Translocation?
A sequence of bases is moved from one location in the genome to another.
This could be a movement within the same chromosome or a movement to a different chromosome.
How could a mutation change the amino acid sequence?
The order of DNA Bases codes for the amino acid sequence. So mutations COULD, but not always, change the amino acid sequence.
Polypeptides make up proteins. A change in the sequence for the polypeptides might change the tertiary structure (final 3D shape) of the protein. This could make the protein un-useful.
A mutation in a enzyme may change the shape of the enzymes active site and make it unable to attach to substrates, therefore making it unable to catalyse a reaction.
What are genetic disorders and how are they caused?
Some mutations can cause genetic disorders.
Genetic disorders are inherited disorders caused by abnormal genes or chromosomes (e.g. cystic fibrosis).
Some mutations increase the likelihood of developing a certain cancer. E.g. mutation of the gene BRCA1 can increase the chances of developing breast cancer.
What are hereditary mutations and how do they occur?
If a gamete (sex cell) containing a mutation for a genetic disorder or a type of cancer is fertilised, the mutation will be present in the new fetus.
This is a hereditary mutation because the mutation has passed onto the offspring.
Sometimes hereditary mutations can be beneficial - they drive evolution.
Why do mutations not always effect the order of amino acids?
The degenerate nature of the genetic code means that some amino acids are coded for by more than one DNA triplet.
This means that some mutations will code for the same amino acid and therefore the same polypeptide.
When this happens, it’s called a ‘silent mutation’.
Substitutions do this.
Inversions do this too.
But additions, duplications and deletions will almost always change the amino acid sequence. This is because these mutations change the number of bases in the DNA code which means a frameshift occurs in the bases that follow the mutation.
This means the triplet code is read differently.
What are the mutagenic agents and how do they increase mutations?
Mutations occur spontaneously, e.g. when DNA is misread during replication.
Mutagenic agents - anything that increases the rate of mutations.
Examples:
- Ultraviolet light,
- Ionising radiation,
- Some chemicals,
- Some viruses.
They increase rate of mutations by:
- Acting as a base - chemicals called base analogs can substitute for a base during DNA replication. This changes the base sequence in the nee DNA.
E.g. 5-bromouracil is a base analog that substitutes for thymine and but pairs with guanine (instead of adenine) which causes a substitution in the new DNA.
- 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 with thymine (instead of cytosine).
- Changing the structure of DNA - some types of radiation can change the structure of DNA replication. E.g. UV radiation can cause adjacent (bases next to each-other) thymine bases to pair up together.
Mutations in genes?
So we’ve looked at mutations of nucleotide bases and mutations of gametes.
These are mutations of individual cells AFTER fertilisation.
These are called acquired mutations.
Sometimes mutations can occur in genes that control the rate of mitosis which can cause uncontrollable cell division (tumour).
There are two types of gene that control cell division called tumours suppressor genes and proto-onceogenes.
What is a tumour?
A mass of abnormal cells.
Tumours that invade and destroy surrounding tissue are cancerous.
How can mutations in tumour suppressor genes cause mutations?
Tumour suppressor genes can be inactivated if a mutation occurs in the DNA sequence.
When functioning 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 a tumour suppressor gene, the protein isn’t produced so the cells divide uncontrollably (the rate of division increases) resulting in a tumour.
How can mutations in proto-oncogenes cause mutations?
The effect of proto-oncogene can be increased if a mutation occurs in the 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 a mutation occurs in a proto-oncogene, the gene can become overactive. This stimulates the cells to divide uncontrollably (rate of division increases) resulting in a tumour.
Two types of tumour?
Malignant tumours - cancerous. They usually grow rapidly and invade and destroy tissues. Cells can break off the tumours and spread to other parts of the body in the blood stream or lymphatic system.
Benign tumours - not cancerous. They usually grow slower than malignant and are often covered in fibrous tissue that stops cells invading other tissues. Benign tumours are often harmless, but they can cause blockages and put pressure on organs. Some of these tumours can become malignant.
How do tumour cells differ from normal cells?
Tumour cells have:
- Irregular shape,
- The nucleus is larger and darker than normal cells. Sometimes they have more than one nucleus.
- They don’t produce 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 abnormal methylation?
Methylation means adding methyl (-CH3) group onto something.
Methylation of DNA is an important method for regulating gene expression - it can control whether or not a gene is transcribed (copied into mRNA) and translated (turned into a protein).
When methylation is happening normally, it plays a key role in many processes in the body. However, when it happens too much (hypermethylation) or too little (hypomethylation), it becomes a problem.
The growth of tumours can be caused by abnormal methylation of certain cancer-related genes:
1. When tumour suppressor genes are hypermethylated, the genes are not transcribed. So the proteins they produce to slow cell division aren’t made. This means that cells can divide uncontrollably and tumours can develop.
- When proto-oncogenes are hypomethylated, they act as oncogenes - increasing the production of proteins that encourage cell division. This stimulates cells to divide uncontrollably which can cause tumours.
How can increased oestrogen contribute to breast cancer?
Increased exposure to oestrogen over an extended period of time is thought to increase a woman’s risk of developing cancer.
Increased exposure may be the result of staring mensuration earlier than normal or the menopause later than usual. It could also be the result of taking oestrogen-containing drugs such as HRT.
The reasons behind why this can cause Brest cancer aren’t fully understood but there’s a few theories:
1. Oestrogen can stimulate certain breast cells to divide and replicate. The fact that more cell divisions are taking place naturally increases the chance of a mutation occurring, and so increases the development of cancerous ones.
- This ability to stimulate division could also mean that if cells do become cancerous, their rapid replication could be further assisted by oestrogen, helping turnouts to form quickly.
- Other research suggests that oestrogen is actually able to introduce mutations directly into the DNA of certain breast cells, again increasing the chance of these cells becoming cancerous.
Risk factors for cancer?
Genetic risk factors - some cancers are linked with specific inherited alleles. If you inherit that allele, your more likely to get that type of cancer (but it doesn’t mean you’ll definitely get it).
Environmental risk factors - exposure to radiation, lifestyle choices like smoking, increased alcohol intake, high-fat diet have all been liked to increased risk of developing cancers.
Why is it difficult to draw conclusions on
the causes of cancers?
Data on variation (cancers) can be tricky to interpret because some characteristics can be affected by different genes (they’re polygenic) and many environmental factors.
It’s hard to know what factors are having the greatest effect - or any effect at all.
This makes it hard to drawn conclusions.
E.g. there’s a positive correlation (on graph example in book) between breast cancer in women and number of first-degree relative (mothers, sisters, daughters) who have also had breast cancer. The effect of family history decreases with age, but is still valid. This shows a genetic link.
Another graph shows a positive correlation between both age and breast cancer and another positive correlation between alcohol consumption and breast cancer. Alcohol is a environmental factor.
It’s difficult to tell which factor has the greatest effect (alcohol or genes).
There are other environmental factors (extraneous variables) that are not measured which could have an effect. Like diet and exercise.
Why knowing the mutation type is useful for preventing cancer?
Cancer is caused by mutations in proto-oncogenes and tumour suppressor genes.
Understanding the role of these genes in causing cancer and knowing how they work helps us understand ways to prevent it.
- If a specific cancer causing mutation is known, then it’s possible to screen for the mutation in a persons DNA (e.g. possible to screen for mutated allele for the BRCA1 tumour suppressor gene, which increases woman’s risk of developing breast cancer.
- Knowing about this increased risk means that prevention steps can be taken. E.g. If we know a woman has the BRCA1 mutation, she can have a mastectomy (removal of one or both breasts) to reduce the risk. Women with this mutation will get regular screening for signs of breast cancer because early diagnosis increases chances of recovery.
- Knowing about specific mutations also means more sensitive tests can be developed which can lead to earlier diagnosis. E.g. there’s a mutation in the RAS proto-oncogene in around half of all bowel cancers. Bowel cancer can be detected early by looking for the RAS mutations in the DNA of bowel cells.
