Mutations and Gene Expression Flashcards
Types of mutations:
Substitution Deletion Addition Duplication Inversión Translocation
What is a mutation?
Change to the base sequence of DNA - caused by errors during DNA replication.
Some mutations can cause…
Genetic disorders - inherited disorders caused by abnormal genes or chromosomes.
What are hereditary mutations?
If a gamete has a genetic disorder or cancel and then it is fertilised, passed on to offspring.
Why do additions, duplications and deletions almost always cause a change in the amino acid sequence?
Because these change the number of bases in the DNA code - causes a frameshift so the triplet code is read in a different way.
How can mutagenic agents increase the rate of mutation?
- chemicals called base analogs can substitution a base, changing base sequence.
- chemicals can delete or alter bases.
- changing the structure of DNA which causes problems during DNA replication.
Mutations that occur after fertilisation…
Acquired mutations
What happens if mutations occur in genes that control the rate of cell division?
Causes uncontrolled cell division - resulting in a tumour (mass of abnormal cells)
Two genes which control cell division:
- tumour suppressor genes
- proto-oncogenes
How can tumour suppressor genes be affected?
If a mutation occurs in the DNA sequence, they can be inactivated.
This means the proteins they make can to be produced so cells divide uncontrollably.
What do Tumour suppressor genes do?
They slow cell division by producing proteins that stop cells dividing or cause them to self destruct.
What do proto-oncogenes do?
They stimulate cell division by producing proteins that make cells divide.
How can proto-oncogenes be affected?
If a mutation occurs in the DNA sequence and in it, gene can become overactive so cells divide uncontrollably.
What is a muted proto-oncogene called?
Oncogene
Malignant tumours
Cancers - grow rapidly and destroy surrounding tissues, can break off and spread to other parts via bloodstream or lymphatic system.
Benign tumours
Not cancerous - grow slower and are covered in fibrous tissue that stops cells invading other tissues, harmless but can cause blockages and put pressure on organs.
How do tumour cells differ from normal cells? (4)
- irregular shape
- nucleus is larger and darker
- different antigens
- divide by mitosis more frequently
What is methylation?
Why is it important?
Adding a CH3 group onto something - this is important for regulating gene expression, can control whether or not a gene is transcribed.
What happens when methylation is happening normally?
It plays a key role in many processes
But when it happens too much or too little, it becomes a problem.
Hypermethylation
When methylation happens too much
Hypomethylation
When methylation happens too little
What happens when tumour suppressor genes are hypermethylated?
The genes are not transcribed, proteins to slow cell division not made - cells grow uncontrollably.
What happens when proto-oncogenes are hypomethylated?
They act as oncogenes - increasing the production of proteins that encourage cell division - cell divides uncontrollably leading to tumour.
Increased exposure to oestrogen…
Increases a woman’s risk of developing breast cancer.
How does oestrogen contribute to the development of breast cancer? (3)
- oestrogen stimulate some breast cells to divide and replicate - more divisions increases mutations so more chance of cancerous cells.
- stimulating division means if cells do become cancerous, their rapid replication forms tumours.
- other research shows it may be able to introduce mutations directly to breast cells.
Genetic factors of cancer
Some cancers are linked to specific alleles - if you inherit it, more likely to get it
Environmental factors of cancer
Radiation
Smoking
Alcohol
High fat diet
Mastectomy
Removal of one or both beasts
Gene therapy
Where faulty alleles in a persons cells are replaced by working versions of the alleles
Stem cells are..
Unspecialised cells that can developed into any other cells.
Stem cells found
Embryo
And some adult tissues
Totipotent stem cells
Only present in mammals in the first few cell divisions of an embryo
Multipotent stem cells
Able to differentiate into a few diff types of cells
Unipotent stem cells
Can only differentiate into one type of cell
How do stem cells become specialised?
- stem cells all contain same genes but not all of them are expressed = some are expressed, some switched off
- mRNa only transcribed from specific genes so the mRNa gets translated into proteins - they modify the cell and cause it to be specialised.
Red blood cells production from a stem cell
Produces a new cell in which the genes for Haemoglobin production is expressed, removing nucleus is expressed.
Cardiomyocytes
Heart muscle cells that make up a lot of the tissue in our hearts
For ages everyone thought…
That we weren’t able to regenerate our heart cells - this is a problem if heart attack occurs etc
Some scientists now think that…
Old or damaged cardiomyocytes can be replaced by new cardiomyocytes derived from a small supply of unipotent stem cells in the heart.
Bone marrow contains
Stem cells that can become specialised to form any type of blood cell.
Bone marrow transplants can be used to…
Replace the faulty bone marrow in patients that produce abnormal blood cells - stem cells in the transplanted can divide and specialise to produce healthy blood cells.
Bone marrow transplants have already treated…
Leukaemia
Lymphoma
SCID
What is SCID
Severe combined immunodeficiency
Treatment:
Genetic disorder that affects the immune system - people with it have defective white blood cells so they can’t fight against infections.
Bone marrow transplant can be used to produce white blood cells - immune system functions
Stem cells can be used to treat: (3)
- spinal cord injuries to replace nerve tissue
- bladder conditions, can grow whole bladders
- organ transplants, organs can be grown from stem cells
2 advantages of stem cells:
- can save many lives
- improve quality of life for many
3 sources of stem cells:
- adult bone marrow
- embryo
- induced pluripotent stem cells
Adult stem cells
Bone marrow
Simple operation, little risk
But can only specialise into limites range of cells
Embryonic stem cells
Embryos via IVF
Stem cells removed and embryo destroyed
Can divide into all types of body cells
Induced pluripotent stem cells
IPS
Reprogrammes specialised adult body cells to become pluripotent
Made to express transcription factors usually associated with stem cells, causing the body cells to express genes assosciated with pluripotency.
How can transcription factors be introduced to the adult cells?
Infecting then with a specially modified virus - this virus has the genes coding for the transcription factors within its DNA
When virus infects adult cells the genes are passed into the adult cell’s DNA so the cell is able to produce the transcription factors
Ethical issues with embryonic stem cells (2)
- embryo right to life, destruction of embryos raises controversy
- believe they should use adult cells instead but they’re only multipotent
Why do all cells have the same genes but have different structures and functions?
Because different genes are expressed
The transcription of genes is controlled by…
Protein molecules called transcription factors
How do transcription factors work in eukaryotes:
- they move to nucleus from cytoplasm and bind to speeding DNA sites near the start of their target genes
- control expression by controlling rate of transcription
Activators
Transcription factors which work to stimulate or increase the rate of transcription
By helping RNA polymerase bind to the start of the target gene and activate transcription
Represora
Transcription factors which inhibit or decrease the rate of transcription
By binding to the start of the target gene and preventing RNA polymerase from binding, stopping transcription.
How can oestrogen affect the expression of genes:
- can bind to a transcription factors called oestrogen receptors forming an oestrogen-oestrogen receptor complex
- this complex moves from the cytoplasm into the nucleus where it binds to specific dna sites next to target gene
- acts as an activator for transcription
Oestrogen is a …
Steroid hormone
Gene expression is also effected by…
RNA interference
RNAi
RNAi is where…
Small, double stranded RNA molecules stop mRNA from target genes being translated into proteins.
Molecules involved in RNAi:
sIRNA
miRNA
How does sIRNA and miRNA work in plants? (3)
- when mRNA is transcribed, leaves the nucleus and double stranded sIRNA assosciates with several proteins and unwinds - a single strand then binds to target mRNA (complentary)
- proteins associated with the 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
How does miRNA work in mammals?
- in mammals, the miRNA isn’t usually fully complementary to the target mRNS - less specific so targets more than one mRNA.
- assosciatts witn proteins and binds to target MRNA.
- mRNA- protein complex physically blocks the translation of target mRNA
- the mRNA is moved into a processing body where it can be either stores or degraded.
Epidemic control can determine…
Whether a gene is switched on or off
How does epigenetic control work?
Through the attachment or removal or chemical groups - epigenetic marks
What do epigenetic marks do?
Don’t alter the base sequence of DNA - they alter how easy it is for the enzymes and other proteins needed for transcription to interact with and transcribe the DNA.
Can epigenetic changes be inherited by offspring?
The marks are usually removed but some escape and are passed to offspring - causes he expression of some genes in the offspring can be affected by environmental changes that affected their parents.
One method of epigenetic control:
- when a methyl group is attached to the DNA coding for a gene
- the group always attached at a CpG side, increased methylation changes the DNA structure so that the transcriptional machinery can’t interact with the gene - gene not expressed.
What is the CpG site?
Where a cytosine and guanine base are next to eachother in the DNA.
Histones
Proteins that DNA wraps around to form chromatin which makes up chromosomes
Chromatin can be highly condensed or not - it affects the accessibility of the DNA
Decreased acetylation effect: (3)
- Histones can be epigenetically modified by addition or removal of acetylene groups
- when they are acetylated, chromatin is less condensed means that the transcription machinery can not access DNA
- when acetyl groups are removed from the Histones, the chromatin becomes highly condensed and genes in the DNA can’t be transcribed because the transcriptional machinery can’t access them.
Histone deacteylase:
Enzymes are responsible for removing the acetyl groups
Twin studies can help us to…
Determine the influences on phenotype from the environment
How can drugs be able to treat diseases caused by epigenetic changes: (2)
HDAC inhibit drugs can work by inhibtating the activity of histone de acetyl ase enzymes which are respinsible for removing the acetyl groups from Histones.
Drugs that stop DNA methylation can sometimes be used to treat diseases caused because of increased methylation.
