Gene expression Flashcards
What is a genetic mutation?
- Alteration in a base in a base sequence
- Occurs during DNA replication during interphase
Explain the effect of genetic mutation
- Change in the base sequence = change in the amino acid sequence = modified 3’
- Bonds form in different places = different shape = non-functioning protein
- Can also result in cancer
Examples of mutagenic agents
- Radiation: Alpha/Beta/Gamma/X-ray can damage and disrupt DNA structure
- Carcinogen: Tobacco smoke/ Mustard gas/ Peroxide chemicals that can interfere with DNA structure + transcription
How many types of genetic mutations?
6 types:
1) Addition
2) Deletion
3) Substitution
4) Inversion
5) Duplication
6) Translocation
Describe addition mutation
- Extra base added
- Causes frameshift to right
- Altered codons = code for multiple different amino acids = different amino acid sequence = non-functional protein
Describe deletion mutation
- Deletion of a base
- Causes frameshift to left
- Altered codons = code for different amino acid sequence = non-functional protein
Describe substitution mutation
- 1 base swapped for another
- Number of bases stays same = no frameshift = only 1 codon changes
- Genetic code = degenerate = 1 codon could still code for same amino = no impact to protein
Describe inversion mutation
- Section of bases detach from DNA sequence but when re-attaching = inverted = code read back to front
- Can cause different amino to be coded for that region
Describe translocation
- Section of bases detaches from 1 chromosome and attaches to another chromosome
- Causes significant difference on gene expression = phenotype change
What is a stem cell?
Undifferentiated cells that can continually divide and become specialized
Describe a totipotent cells
- Divide and produce any type of body cell
- During development these cells only translate only 1 part of their DNA = specialization
- Occur for a limited time in early embryo
Describe pluripotent cells
- Divide and produce ALMOST any body cell
- Found in embryo a few days after fertilization
Uses of pluripotent cells
- Used in research to potentially use in treating human disorders
- Could be used to regrow damaged cells e.g. burnt skin, beta cells for diabetes, neurons in Parkinson’s
Issues with pluripotent cells
- Treatment with stem cells can continue dividing causing uncontrollable growth = create tumor
- Ethical: If it is ok to make a therapeutic clone of yourself + make embryo for stem cells then to destroy it
Describe multipotent cells
- Divide and produce into limited number of cells e.g. all blood cells
- Found in mature mammal cells e.g. bone marrow
Describe unipotent cells
- Divide and produce only 1 type of cell
- Found in mature mammal cells e.g. skin cells
Sources of stem cells
1) Embryos: For a limited time post fertilization = pluripotent
2) Umbilical cord blood: Like adult stem cells = multipotent
3) Placenta: Limited types of specialized cells = multipotent
4) Adult stem cells: Can repair within certain tissue + organs = multipotent/unipotent
Explain induced pluripotent stem cells
- Altering adult unipotent stem cells to make them in the state of pluripotency
- This is done using transcriptional factors
- Similar to embryonic cells without the ethical issue of destroying embryos
What is epigenetics?
- Heritable change in gene function without changing DNA base sequence
- Changes caused by environment
Factors that effect epigenetics
- Diet/Stress/Toxins
- Can add chemical tags to DNA which controls gene expression
What is the epigenome?
Single layer of chemical tags on DNA which impacts the shape of the DNA-histone complex
How does the epigenome effect gene expression?
- If DNA tightly wound = won’t be expressed
- If DNA unwound = will be expressed
- Tightly wound = transcription factors cannot bind = changes from the environment to epigenome = inhibits transcription
Explain methylation of DNA
- Increase = tightening = inhibits transcription
- Methyl group attaches to cytosine
- Prevents transcriptional factors from binding
Explain acetylation of DNA
- Decrease = tightening = inhibits transcription
- Acetyl groups attach/detach from histone proteins
- Makes DNA + histone more strongly associated = harder for transcriptional factors to bind
Explain how mutations effects tumor suppressor genes
- Mutation = don’t produce proteins to slow down cell division = division continues
- Mutated cells not identified and destroyed
- Causes BRCA1/BRCA2 linked to breast cancer
Explain how abnormal methylation effects tumor suppressor genes
- Hypermethylation: Increased number of methyl groups = tightens = inhibits transcription = gene inactivated
- Hypomethylation: Reduces number of methyl groups = causes oncogenes that control mitosis = permanently turned on = continuous cell division
Function of transcriptional factors
- Stimulate/inhibit transcription of target genes
- Turn on/off genes so only certain proteins are produced in particular cells
- This causes cells to become specialized
Explain how transcriptional factors affect transcription in protein synthesis
- Once activated transcriptional factor proteins move into the nucleus
- Bind to different base sequences that they are complementary to
- Binding = enables RNA polymerase binding = transcription starts = mRNA made
Explain how estrogen initiates transcription
- It is a steroid hormone that binds to the receptor site on the transcriptional factor
- This causes a change in shape/ 3’ = TF now complementary and able to bind to DNA = initiates transcription
Describe RNA interference
- Translation of mRNA is inhibited
- Transcribed mRNA is destroyed before it can be translated into a polypeptide by siRNA
Describe how siRNA works
-Enzyme cuts mRNA into siRNA
- 1 strand of siRNA combines with an enzyme
- The siRNA/enzyme complex binds to complementary bases on another mRNA
- Binding = cutting up of mRNA = cannot be translated
What is cancer?
- Mutation occurs in genes that are involved in mitosis
- Mutation = non-functioning protein = unregulated mitosis = uncontrollable cell division = tumor
Describe benign tumors
- Non-cancerous
- Can grow large but at a slow rate
- Produce adhesive molecules that stick them together to a particular tissue
- Surrounded by capsule = compact = easier to remove by surgery
- Impact is localized = not life-threatening depending on location
Describe malignant tumors
- Cancerous
- Grow large and rapidly as the cell nucleus grows and becomes unspecialized again
-Don’t produce adhesive molecules = metastasis = tumor breaks off and spreads - No surrounding capsule = grows into surrounding tissue = develops it’s own blood supply
- Threat of spread = life-threatening so treatment required is extensive and can reoccur
What causes tumor development?
1) Mutated oncogenes
2) Mutated tumor suppressor genes
3) Abnormal methylation
4) Increased estrogen concentration
Explain how a mutation in oncogenes causes tumor development
- Proto-oncogene: Code for protein that initiates DNA replication/mitosis
- Mutated proto-oncogene = oncogene = permanently activated = uncontrollable cell division = tumor
Explain how a mutation in tumor suppressor genes causes tumor development
- Tumor suppressor genes: Code for proteins that slow down cell division + cell death if there is copying errors
- Mutated gene = protein not produced = uncontrollable cell division + mutated cells not identified and destroyed = tumor
Explain how abnormal methylation causes tumor development
- Hypermethylation of tumor suppressor gene: Increases methyl groups = tightening = inactivates gene = turned off = protein not produced = cell division continues = tumor
- Hypomethylation of oncogene: Decrease methyl group = loosening = gene permanently switched on = cell division continues = tumor
Explain how increased estrogen concentrations cause tumor development
- Estrogen is produced in fat cells in breast tissue post menopause
- Estrogen can interfere with the genes in the cell cycle = tumor
- Tumor can cause production of even more estrogen + attract WBC = increased tumor size
What is a genome?
Entire genetic material of an organism in the nucleus of a cell
What is genetic sequencing?
Working out the DNA base sequence for all the DNA in a cell
Describe genome sequencing
- HGP took 13 years to complete in 2003
- Methods for sequencing are continuously being improved and updated
- Now an automated process
Describe genome sequencing for simpler organisms
- DNA doesn’t contain introns = genome can be used to sequence proteins = derive proteome
- Useful to identify potential antigens for vaccines
Describe genome sequencing for complex organisms
- DNA has introns and regulatory genes = genome cannot easily be translated into proteome
