8a mutations and gene expression Flashcards
What are mutations?
Changes to a base sequence of dna
What are the 6 types of mutations (name) ?
Substitution
Deletion
Addition
Duplication
Inversion
Translocation
What is a substitution mutation?
One or more bases swapped for another
What is a deletion mutation?
One or more bases removed
What is an addition mutation?
One or more bases added
What is an inversion mutation ?
A sequence of bases reversed eg ATGCCT becomes ATCGGT
What is a translocation mutation ?
A sequence of bases is moved from one location in the genome to another by movement within the same chromosome or movement to a different chromosome
How can a mutation cause a change in the polypeptide formed ?
Changes tertiary structure
Active site changes
Stops substrates from being able to bind
Enzyme can no longer catalyse reaction
What is a hereditary mutation?
If a gamete contains a mutation for a type of cancer or genetic disorder the mutation will be present in the new fetus formed
What is a degenerate mutation and effect ?
Same amino acids are coded for by more than one DNA triplet so it might not cause a change in polypeptide
What is a frameshift mutation?
Triplet code read in a different way when an addition, deletion and duplication mutation are present
What are mutagenic agents?
Things that increase rates of mutations eg UV, radiation, chemicals
How do mutagenic agents change the rate?
Acting as a base
Altering bases
Changing the structure of DNA
What is an acquired mutation?
Occur in individual cells after fertilisation
What are tumours ?
Uncontrollable cell division
What are the two types of genes that control cell division?
Tumour suppressor genes
Proto oncogenes
What does a tumor suppressor gene do ?
Slow cell division by producing proteins that stop cells dividing or cause self destruction
What is the effect of a mutation on tumor suppressor genes?
The gene will be inactivated so the protein it codes for isnt produced and the cell divides uncontrollably
Mutation (in tumour suppressor genes);
Tumour suppressor genes are not transcribed/expressed
Amino acid sequence/primary structure altered
(Results in) rapid/uncontrollable cell division;
What does a proto oncogenes do?
stimulate cell division by making proteins that make cells divide
What is the effect of a mutation on proto oncogenes?
Gene becomes overactive so they divide uncontrollably
What is the name of a mutated proto oncogene?
Oncogene
What are the 2 types of cancers?
Benign
Malignant
What is the difference between the two types of cancers?
Malignant
- cancers
- rapidly grow
- invade and destroy surrounding tissue
Benign
- not cancerous
- grow slower and often covered in fibrous tissue that stops cells invading other tissues
- cause blockages and puts pressure on organs
How do tumour cells differ from normal cells ?
Nucleus is larger
Irregular shape
Don’t produce all proteins needed to function
Different antigens on surface
Don’t respond to growth regulating processes
Divide by mitosis more frequently
What are the two causes of tumour growth?
- Abnormal methylation of DNA
- Increased exposure to oestrogen
How does abnormal methylation cause tumour growth?
By it occurring too much (hypermethylation) or too little (hypomethylation)
What is hypermethylation and how does it relate to tumour growth?
Tumour suppressor genes are hypermethylated so the genes are not transcribed - so the proteins they produce to slow cell division are not made
What is hypomethylation and how does it relate to tumour growth?
Protooncogenes causes them to act as oncogenes increasing protein production that encourage cell division
What is the role of oestrogen in breast cancer?
- stimulate certain breast cells to divide and replicate
- their rapid replication could be further assisted by oestrogen helping tumours form quickly
- oestrogen can introduce mutations directly into DNA of breast cells
What are the 2 risk factors for cancer?
Genetic
Environmental
How can you prevent cancer?
Screen for mutation in the DNA
More sensitive tests done so more accurate diagnosis
How can you treat and cure cancer ?
- drugs that can bind to protein receptor suppressing divison and tumour growth
- blocking enzymes that are involved in dna repair
- radiotherapy
- surgery
- gene therapy
what are stem cell?
They are unspecialised stem cells that can divide to become new specialised cells
What are some specialised cells?
Nerve
Muscle
Where are stem cells found ?
embryo - stem cells to become specialised
adult tissues - stem cells to be replaced
What are totipotent cells and when are they present ?
Stem cells that can mature into any type of body cells and are present in the first few cell divisions of an embryo
What are pluripotent cells ?
They can still specialise into any cell in the body but lose the ability to become the cells that make up the placenta
What is the difference between multipotent and unipotent cells?
Multipotent are able to differentiate into a few different types of cells
Unipotent can only differentiate into one type of cell
How does a cell become specialised ?
- Genes are expressed
- mRNA transcribed and translated into proteins
- Proteins modify the cell
- Cell becomes specialised for a particular function
What is the name of the heart muscle cell
cardiomyocyte
What type of stem cell can replace old cardiomyocytes ?
Unipotent stem cells
What is a bone marrow transplant and what diseases has it treated ?
Bone marrows contain stem cells that can become specialised to form any type of blood cell
Replace the faulty bone marrow that produce abnormal cells
leukaemia, lymphoma, sickle cell anaemia
How does stem cell therapy help spinal cord injuries ?
Replace damaged nerve tissue
How does stem cell therapy help heart disease?
Replace damaged heart tissue
How does stem cell therapy help bladder conditions?
Grow whole bladders, which are implemented to replace diseased ones
How does stem cell therapy help respiratory diseases ?
Donated windpipes can be stripped to simple collagen structure and covered with tissue generated by stem cells
What are the 3 sources of stem cells and what do they do ?
- Adult stem cells - found in bone marrow to specialise into limited range if cells
- Embryonic stem cells - created using IVF
- Induced pluripotent stem cells - reprograming adult stem cells to become pluripotent so they can express a series of transcription factors
In IPS what is the way transcription factors can be introduced to adult cells?
By infecting them with a specially modified virus
The virus has the genes coding for transcription factors within dna
When virus infects the genes are passed into adult cells dna so it can produce the transcription factors.
What are the ethical considerations to do with stem cells ?
- getting stem cells created by IVF raises issues because the procedure destroys embryos
- that adult stems cells can not specialize like embryonic
What are the benefits of stem cell therapy ?
- save lives as allows organs to grow for those awaiting transplant
- make stem cells genetically identical to a patients own cells which can be used to grow some tissue
- improve quality of life
What is transcription?
When a gene is copied from DNA into messenger RNA
What are transcription factors?
These are protein molecules that control the rate of transcription of genes
What does the transcription factor bind to in the nucleus?
Promoters which are specific dna sites
What are the activators?
These are transcription factors that stimulate or increase the rate of transcription
What is the role of activators ?
They help RNA polymerase bind to start of the target gene and activate transcription
What is repressors?
Inhibit or decrease the rate of transcription by binding to the start of target gene preventing RNA polymerase from binding, stopping transcription
How does oestrogen affect transcription?
It binds to a transcription factor called an oestrogen receptor forming an oestrogen-oestrogen receptor complex
Where does the oestrogen-oestrogen receptor complex bind and move too?
Moves from the cytoplasm into the nucleus where it binds to specific dna sites near the start of the target gene.
What does the oestrogen-oestrogen receptor complex act as?
The complex can act as an activator of transcription eg helping rna polymerase bind to start of the target gene
What is RNAi?
RNA interference is where small double stranded RNA molecules stop mRNA from target genes being translated into proteins
What are the molecules involved in RNAi?
siRNA ( small interfering RNA )
miRNA ( microRNA)
What are the steps for how RNAi works ? (siRNA and miRNA in plants)
- Once mRNA has been transcribed, it leaves the nucleus for the cytoplasm
- In the cytoplasm double stranded siRNA associates with several proteins and unwinds
- One of the resulting single strands of siRNA is selected and the other strand broken down
- The single strand of siRNA binds to target mRNA.
- The base sequence of siRNA is complementary to base sequence in sections of target mRNA.
- The proteins associated with the siRNA cut mRNA into fragments
- Fragments move to processing body and are degraded.
What is the role of the miRNA in mammals?
- When miRNA is first transcribed it exists as a long folded strand –> processed into a double strand–> 2 single strand
- One strand associates with proteins and binds to target mRNA in the cytoplasm
- Now instead, the miRNA complex physically blocks translation of target mRNA
- The mRNA is then moved into a processing body where it is stored or degraded
How does epigenetic control work?
Determines whether a gene is switched on or off by attachment or removal of chemical groups to or from DNA or histone proteins
What does the epigenetic marks alter?
How easy it is for enzymes and other proteins needed for transcription to interact with and transcribe DNA
What are the 2 ways to control gene expression?
Increased methylation of DNA
Decreased acetylation of histones
What is increased methylation of DNA ?
When a methyl group is attached to the DNA coding for a gene
- The group attaches at a CpG site (cytosine - phosphodiester - guanine)
- This changes DNA structure so that the transcriptional machinery cant interact with the gene = SWITCHED OFF
What is histones?
Histones are proteins that DNA wraps around to form chromatin
What happens when histones are acetylated?
The chromatin is less condensed so transcriptional machinery can access DNA so genes can be transcribed
What affects the access of DNA?
Whether chromatin is highly condenses or less condensed therefore affecting whether it can be transcribed
What happens when acetyl groups are removed from histones?
The chromatin becomes highly condensed and genes in the DNA cant be transcribed because the transcriptional machinery cant physically access them
What enzymes are responsible for removing acetyl groups?
Histone Deacetylase
How does epigenetics cause Fragile X syndrome ?
Mutation on the X chromosome where the sequence CGG is repeated many times so there are more CpG sites –> more methylation –> switches off so lack of protein –> disease
How does epigenetics cause Angelman Syndrome ?
Deletion of region 15
mainly on maternal allele
gene switched off by methylation –> motor and delay problems
How does epigenetics cause Prader willi syndrome?
loss of functions on gene of chromosome 15
occurs when deletion occurs on paternal chromosome
maternal gene silenced by methylation so can not compensate
How do you treat Epigenetic diseases?
Drugs to stop DNA methylation
Decreased acetylation of histones –> inhibit histone deacytylase enzymes
What is the phenotype?
Result of organisms genotype and interaction of its genotype with the environment
