Topic 8 - Control Of Gene Expression Flashcards
What is a mutation and name the types of mutations
- changes base sequence of dna and affects structure and function of proteins and can cause genetic disorder
- substitution
- deletion
- substitution
- addition
- duplication - one or more bases repeated
- degenerate - no change on amino acid
- inversion - base sequence reversed
- translocation - base sequence moves from one loci on the gene to another
How can mutations affect proteins
- change amino acid sequence
- change tertiary structure
- change function or cause it to not work properly
Hereditary mutation
Mutation in gamete that’s developed in the fertilised foetus
- not all are harmful
Silent mutation
Degenerate - no change due to more than one base sequence that can code for the same amino acid
- can be caused by substitution
Frameshift
Additions, deletions or duplications cause framshift
- change in all amino acids from the point of the mutation
Mutagenic agents
- increase rate of mutation
- ultraviolet radio action
- Ionising radiation
- chemicals
How do mutagenic agents increase rate of mutations
- act as a base - substitution and changing base sequence
- altering bases - some chemical delete or alter bases
- change structure of dna - cause problems during dna replication
How do mutations lead to cancer
Uncontrolled cell growth and division leading to a tumour
Acquired mutations
Mutations in individual cells after fertilisation (in adulthood)
Tumour
Invade and destroy surrounding tissue
Types of genes controlling cell division?
Tumour suppressor genes
Proto-oncogenes
- mutations in these genes causes cancer
TSG
Tumour suppressor gene
- inactivated if mutation occurs in dna sequence
- function = to slow cell division (and cause cells to self-destruct)
- mutation in TSP = no protein produced and cell divided uncontrollably causing tumour
- breaks - if brakes not working, division can’t be stopped
Proto-oncogene
- mutated POG = oncogene
- effect of POG increased if mutation in dna sequence
- normal function = stimulates cells division by producing proteins that make cells divide
- mutation overactives POG stimulating uncontrolled division leading to tumour
- accelerator - if mutation occurs acceleration will increase
Malignant
Rapid growth
Invade and destroy surroundings tissue
Cells can break off tumour and spread into blood and lymph systems all around the body
Benign
Not cancerous
Slower growth
Fibrous tissue surrounding it stops invasion of other tissues
Harmless
Can cause blockages and increased pressure
Can become malignant
How are tumour cells different to normal cells
- irregular shape
- larger darker nucleus
- don’t produce all proteins needed to function correctly
- different antigens on surface
- don’t respond to growth regulating processes
- ## Divide by mitosis more frequently
Methylation
Adding methyl groups
-CH3
Methylation of DNA
- regulates gene expression
- control if a gene is transcribed (copied form mRNA)/ translated (turned into protein) or not
- normal body function at normal rate
HypERmethylation
- methylation happening too much
HypOmethylation
Too little methylation
Abnormal methylation
Hyp(er/o)methylation
- growth of tumours
TSG hypERmethylated
- genes not transcribed
- proteins to slow division not made
- uncontrolled division
- tumour develops
HypOmethylation of POG
- act as oncogenes
- increased production of genes encouraging cell division
- uncontrolled division stimulated
- formation of tumours
Increased exposure to oestrogen
- increase risk of breast cancer
- cause earlier menstruation or later menopause
Theories behind how oestrogen can contribute to development of some breast cancers
- oestrogen stimulates certain breast cells to replicate
- more division increases changes of mutation and cancerous cells
- quick tumour formation
Factors increasing risk of cancer
- genetic factors like inherited alleles
- environmental factors like radiation, smoking, alcohol, high-fat diet.
Stem cells
Unspecialised cells found in embryos and bone marrow
Totipotent
Specialise into any type of cell
Pluripotent
After first division of embryo
- specialise into any cells but lose ability to become cells that make up placenta
Multipotent
Adult mammals
- differentiate into few types of cells
- e.g. RBC + WBC
- found in bone marrow
Unipotent
- differentiate into one type of cell
- epidermal skin cells
What causes specialisation
- differnt genes expressed
- during development, not all gene transcribes and translated
- some express some switched off
- mRNA only transcribed for specific genes
- some proteins made which determine structure and control cell processes
- changes to cell caused by proteins causes specialisation
- difficult to reverse
RBC
Red blood cells
- from bone marrow
- lots of haemoglobin
- no nucleus
Cardiomyocytes
Heart muscle cells
- do have some regenerative capability
How can stem cells treat human disorders
- bone marrow transplants to treat leukemia and sickle-cell anemia
- spinal cord injuries
- heart disease
- bladder conditions
- respiratory diseases
- organ transplants
Benefits to stem cells medicine
- save lives
- improve quality of life
3 main forces of human stem cells
- adult stem cells
- embryonic stem cells
- induced pluripotent stem cells (iPS cells)
Adult stems
- form body tissues of an adult
- bone marrow
- simple operation with low risk
- lots of discomfort
- adult stem cells not as flexible as embryonic stem cells
- limited specialisation (multi potent)
Embryonic stem cells
- from embryos
- in vitro fertilisation
- pluripotent
Induced pluripotent stem cells
IPS
- reprogramming specialised adult body cells To become pluripotent
- express a series of transcription factors - expressed genes
- introducing transcription factors into adult cells by infecting them with specially-modified virus
- genes then passed into adult cells dna - cell able to produce transcription factors
- useful in research and medicine
Ethical issues in embryonic stem cells treat human use
- stem cells from embryos in IVF results in destruction of embryo that could become a fetus
- right to life
- not fertilised so not violating rights
Why do cells do different things despite having same dna
- all carry same dna
- only some genes expressed and transcribed to make specific proteins
- different genes = different proteins = determine cells structure and control cell process
Transcription factors
- proteins that control transcription of genes
How transcription factors work
- move from cytoplasm to nucleus
- bind to specific DNA sites near start of TARGET GENES (the genes they control the expression of)
- control rate of transcription (activators increase, depressors inhibit)
Activators
- transcription factors that stimulate or increase the rate of transcription
- help RNA polymerase bind to target gene and activate transcription
Repressors
- transcription factors inhibiting or decreasing rate of transcription by binding to start of target gene preventing RNA polymerase from binding and stopping transcription
Oestrogen
- can affect gene transcription
- steroid hormone
- binds to transcripts factor (oestrogen receptor) forming oestrogen-oestrogen receptor complex
- complex moves from cytoplasm to nucleus where it binds to specific DNA sites near start of target gene preventing RNA
- activator so helps RNA polymerase
What is RNAi
RNA interference
- inhibit translation of mRNA
- small soluble double- strand of rna that stops mRNA from target genes being translated into proteins
- in euks and similar in proks
- siRNA also involved (small interfering RNA) and miRNA (microRNA)
How does RNAi work (siRNA and miRNA in plants)
- once mRNA transcribed it leaves nucleus for cytoplasm
- siRNA associates with proteins and unwinds
- single strand binds to target mRNA (complimentary)
- proteins associated with siRNA but mRNA into fragments so can’t be translated
- fragments move to translating body which degrades them
- similar process in miRNA in plants
MiRNA in animals
- not fully compliamentary to target mRNA
- less specific than siRNA (can target more than one mRNA molecule)
- associates with proteins and binds to target mRNA in cytoplasm
- miRNA-protein complex physically blocks translation (not cutting)
- mRNA moved to translation body and stored or degraded
When stored can return and be translated another time
