20. Gene Expression Flashcards
Name all the gene mutations
- Substitution
- Deletion
- Addition
- Duplication
- Inversion
- Translocation
Name 3 consequences of gene substitution
- One of the 3 stop codons are formed which prematurely stops the production of the polypeptide chain. This results in a significantly different protein that wouldn’t be able to function properly
- Another codon is formed, which codes for a different amino acid. This change in the polypeptide chain may cause a change in the proteins tertiary structure meaning the protein produce will be dysfunctional.
- The formation of different codon but codes for the same amino acid. This is because the genetic code is degenerate. It will have no effect on the overall protein shape/function
What is the consequence of a deletion mutation
- the deletion of a base causes a frameshift for every codon downstream of the mutation
- this alters most triplets downstream meaning the amino acids coded for are different
- significantly altering the proteins tertiary structure and therefore its dysfunction.
Define substitution
Type of gene mutation in which a nucleotide in a section of a DNA molecule is replaced by another nucleotide.
Define deletion
The loss of a nucleotide base from a DNA molecule
Define addition
When an extra nucleotide base is inserted into the DNA molecule
What is the consequence of an addition mutation
- the addition of a base causes a frameshift for every codon downstream of the mutation
- this alters most triplets downstream meaning the amino acids coded for are different
- significantly altering the proteins tertiary structure and therefore its dysfunction.
Why is a deletion/addition of 3 bases less detrimental to the proteins tertiary structure
- there will not be a frameshift
- the protein coded for will be slightly different
- but not as dysfunctional as if there was a frame shift
Define duplication
When one or more nucleotide bases are repeated in a DNA molecule
What is the consequence of a duplication mutation
- the duplication of a base causes a frameshift for every codon downstream of the mutation
- this alters most triplets downstream meaning the amino acids coded for are different
- significantly altering the proteins tertiary structure and therefore its dysfunction
Define inversion
When a small sequence of nucleotide bases becomes separated from the DNA molecule and rejoin at the same position but inverted.
What is the consequence of an inversion mutation
- this portion of the base sequence codes for a completely different set of amino acids
- can cause a dysfunctional protein
Define translocation
- when a group of bases become separated from the DNA sequence on one chromosome
- and become inserted into the DNA sequence of another chromosome
What is the consequence of translocation
- often have significant effects on gene expression
- leading to abnormal phenotype
- can include the development of some cancers and infertility
What are mutagenic agents
Outside factors that increase mutation frequency
Name two mutagenic agents
- high energy ionising radiation
- chemicals
What is cell differentiation
The process where cells become specialised for different functions
Why do all cells in the body have the potential to produce anything the body can make
All cells in an organism are derived by mitotic divisions of the fertilised egg (zygote) so they all contain the same genes
Why is it that cells contain the same genes but produce different things
Only certain genes are expressed at any one time
Give an example of gene that are permanently expressed
The gene that codes for the enzyme in respiration
Give an example of gene that are permanently not expressed
The gene that codes for insulin in the small intestine
Why do differentiated cells differ from each other visibly
- each cell has different genes expressed
- so different proteins are coded for
- giving differences that are visible
Define totipotent stem cells
- a cell which can mature into any body cell, e.g zygotes.
- found in early embryo
Name two ways in which genes are prevented from being expressed
- preventing transcription and so preventing the production of mRNA
- preventing translation
Why can xylem vessels and red blood vessels, specifically, not develop into other cells
They lose their nuclei when they mature and as the nucleus contains the genes they cannot develop into other cells
Define stem cells
Undifferentiated dividing cells that occur in embryos and in adult animal tissues .
Name 4 sources of stem cells in mammals and how they are different
- embryonic stem cells. From embryos in the early stages of development. Can differentiated into any type of cell.
- umbilical cord blood stem cells. From umbilical cord. Specific to a particular tissue or organ within which they produce the cells to maintain and repair tissues
- placental stem cells. From placenta. Develop into specific types of cells
- adult stem cells. Found in the body of fetus to adult. Specific to a particular tissue or organ within which they produce the cells to maintain and repair tissues
Name 4 types of stem cells
- totipotent stem cells
- pluripotent stem cells
- multipotent stem cells
- unipotent stem cells
Define pluripotent stem cells
- can differentiate into almost any type of cell.
- found in embryos.
- eg. embryonic stem cells and fetal stem cells
Define multipotent stem cells
- can differentiate into a limited number of specialised cells.
- usually develop into cells of a particular type (eg. stem cells in the bone marrow can produce any type of blood cell
- e.g adult stem cells and umbilical cord blood stem cells
Define unipotent stem cells
- can only differentiate into a single type of cell
- derived from multipotent stem cells
- made in adult tissue
- e.g cardiomyocytes
What are cardiomyocytes
- a type of unipotent stem cell
- a heart muscle cell that can divide to produce new heart tissue and so repair damage to heart muscle
What does iPS cells stand for
Induced pluripotent stem cells
What are iPS cells
A type of pluripotent that is produced from unipotent stem cells
How are iPS cells produced
- body cells are genetically altered in a lab to make them require the characteristics of embryonic stem cells (a type of pluripotent cell)
- acquiring these these characteristics changes involves inducing genes and transcriptional factors (switching on genes)
What does the fact genes in iPS cells were able to be reactivated show
Adult stem cells retain the same genetic information that was present in the embryo
How are iPS cells different to embryonic stem cells
iPS cells are capable of self renewal. This means they can provide a limitless supply. Could replace embryonic stem cells in medical research which would overcome ethical issues
How may iPS be able to treat human disorders
- cells can be used to regrow tissues that have been damaged
- e.g heart muscle cells (damaged from heart attack), skin grafts, and B cells of the pancreas (Type 1 diabetes).
Before transcription can begin what must first happen
The gene must first be switched on by transcriptional factors
What is are transcriptional factors
Specific molecules that move from the cytoplasm into the nucleus that switch on genes for transcription
How do transcriptional factors switch on genes for transcription
- transcriptional factors have a site that binds to a specific base sequence of DNA in the nucleus
- when it binds it causes the region of DNA to begin the process of transcription
What is happening when a gene is not being expressed (i.e why)
The site on the transcriptional factor that binds to the DNA is not active. This means it cannot bind and cause transcription
Describe briefly how hormones such as oestrogen can switch on a gene
- the hormone combines with the receptor site on the transcriptional factor
- this activates the DNA binding site causing it to change shape
- allowing it to bind to the DNA and begin transcription
Describe in detail the effect of oestrogen on gene transcription
- oestrogen is lipid soluble so diffuse through the phospholipid bilayer of the cell-surface membrane
- oestrogen then binds with a site on a receptor of the transcriptional factor, the site and the shape of the oestrogen molecule are complementary
- binding causes the shape of the DNA binding site on the transcriptional factor to change (it has been activated)
- the transcriptional factor can then enter the nucleus through a nuclear pore and bind to a specific base sequence on DNA
- this stimulates transcription of the gene
Why can oestrogen easily diffuse through the phospholipid bilayer of the cell-surface membrane
Oestrogen is a lipid-soluble molecule
What does oestrogen bind to
A complementary receptor site on the transcriptional factor
What does the binding of oestrogen on the transcriptional factor cause
- causes it to be activated
- the DNA binding site on the transcriptional factor changes shape
- so it is able to bind with DNA
How does the transcriptional factor enter the nucleus
Through a nuclear pore
What is epigenetics
A scientific field studying how environmental influences can alter the genetic inheritance of an organisms offspring
What are DNA wrapped around
Proteins called histones
What are the DNA and histones covered in
Chemical tags
What is the epigenome
The second layer formed from the chemical tags
What does the epigenome determine
The shape of the DNA histone complex and therefore which genes can be expressed
How does the epigenome control the expression of genes
- epigenome determines the shape of the DNA histone complex
- genes that aren’t expressed are inactive in a tightly packed arrangement ensuring they cannot be read
- keeping them switched off which is known as epigenetic silencing
- genes that are active are unwrapped and the DNA is exposed so it can be transcribed
What is epigenetic silencing
When genes aren’t expressed due to the shape of the DNA histone complex due to the epigenome
Name 2 ways transcription can be inhibited by the epigenome caused by environmental factors
- decreased acetylation of histones
- increased methylation of DNA
When association of histones with DNA is weak…
the DNA histone complex is less condensed. DNA is therefore easily accessible to transcription factors
Condensation of the DNA histone complex does what to transcription
Inhibits
What is acetylation
The process whereby an acetyl group is transferred to a molecule.
In the case of acetylation of histones what is donating the acetyl group
acetyl coenzyme A
What does decreased acetylation do to the histone
- increase the positive charges
- therefore increase the attraction to the phosphate groups of DNA
- association between DNA and histones is stronger
- DNA less accessible to transcription factors
- so decreased acetylation means gene is switched off
What is methylation
The addition of a methyl group to a molecule
In the case of methylation of DNA what is the methyl added to
The cytosine bases of DNA
How does methylation inhibit the transcription of genes
- preventing the binding of transcriptional factors to the DNA
- attracting proteins that condense the DNA-histone complex (by inducing deacetylation of the histones) making the DNA inaccessible to transcription factors
How is epigenetics related to disease
- activation or silencing of genes can rise to disease
- e.g cancer
How can diseases be treated with epigenetic therapy
- drugs can be used to inhibit certain enzymes involved in either histone acetylation or DNA methylation
- this can be used to reverse activated or silenced genes causing diseases
Why must epigenetic therapy specifically targeted on diseased cells (e.g cancer cells)
If drugs were to affect normal cells they could activate gene transcription and make them cancerous
Name another use of epigenetics in disease treatment
- can be used in early diagnostic tests that can help detect the early stages of disease
- detecting level of DNA methylation or histone acetylation
- allowing those with these diseases to receive early treatment
Name another way, apart from the prevention of translation, that genes can be not expressed
mRNA from transcription can be broken down before it can be translated into a polypeptide by siRNA
What does siRNA stand for
Small interfering RNA
Briefly how does siRNA work
It pairs with an enzyme and binds to a complementary section of mRNA and cuts it into smaller sections so it cannot be translated
Describe in detail the mechanism of blocking a gene involving siRNA
- an enzyme cuts large double stranded molecules of RNA into smaller sections called siRNA
- one of the two siRNA strands combines with an enzyme
- the siRNA molecule guides the enzyme to a messenger RNA molecule by pairing up its bases with the complementary ones on a section of the mRNA molecule
- the enzyme then cuts the mRNA into smaller sections
- the mRNA is no longer capable of being translated into a polypeptide
- this means the gene has not been expressed (blocked)
How is siRNA made from RNA
An enzyme cuts large double stranded molecule of RNA into smaller sections called siRNA
What is a malignant tumour
A cancerous tumour
What is a benign tumour
A non-cancerous tumour
Name some characteristics of benign tumours
- can grow to large size
- grow slowly
- must less likely to be life threatening but can disrupt organ function
- have localised effect on the body
- cells are often well differentiated
Name some characteristics of malignant tumours
- can grow to large size
- grow rapidly
- more likely to be life threatening as abnormal tissue replaces normal
- have a systemic (whole body) effect such as weight loss and fatigue
- cells become de-differentiated
What happens during the development of cancer
- cancer cells are derived from a single mutant cell
- the initial mutation causes uncontrolled mitosis
- later a further mutation in one of the descendant cells leads to other changes that cause subsequent cells to be different from normal in growth and appearance
Name the two main types of genes that play a role in cancer
- tumour suppressor genes
- oncogenes
What are proto-oncogenes
- genes that stimulate a cell to divide
- when growth factors attach to a complementary protein receptor on its cell surface membrane
- this activates the genes causing DNA to replicate and the cell to divide
How do proto-oncogenes cause the cell to divide
- when growth factors attach to a complementary protein receptor on its cell surface membrane
- it activates the genes causing DNA to replicate and the cell to divide
What happens when a proto-oncogene mutates into an oncogene
It becomes permanently switched on
Why does a proto-oncogene become permanently switched on
- the receptor protein on the cell-surface membrane can be permanently activated so that cell division is switched on even in the absence of growth factors
- the oncogene may code for a growth factor that is then produced in excessive amounts again, stimulating excessive cell division
Name two ways cancer can occur
- mutation of proto-oncogenes
- mutation of tumour suppressor genes
What do tumour suppressor genes do
- slow down cell division
- repair mistakes in DNA
- and ‘tell’ cells when to die (undergo apoptosis)
What is apoptosis
Cell programmed death
How do tumour suppressor genes prevent the formation of tumours
They maintain normal rates of cell division
How can the mutation of tumour suppressor genes cause cancer
- mutation of tumour suppressor gene causes it to become inactive
- as a result it stops inhibiting cell division
- cells growth becomes out of control
- therefore cancer
How does the hypermethylation of tumour suppressor genes cause the formation of a tumour
- hypermethylation in a specific region of tumour suppressor genes (promotor region)
- this leads to inactivation of the gene
- transcription of the promotor regions of the tumour suppressor genes is inhibited
- inactivation means cell growth rate cannot be controlled
- leading to the formation of the tumour
What is hypermethylation
Increased methylation
Why does the hypermethylation of the on the tumour suppressor cause it to be inactivated
- preventing the binding of transcriptional factors to the gene
- attracting proteins that condense the DNA-histone complex (by inducing deacetylation of the histones) making the DNA inaccessible to transcription factors
What other type of abnormal methylation can occur that leads to tumours
- hypomethylation of oncogenes
- therefore activating these oncogenes
- therefore causing the formation of tumours
What happens during menopause
Increased production of oestrogen in fat cells of breasts
How does oestrogen cause a tumour to develop
- oestrogen activates a gene by binding to a transcription factor which stimulates transcription of a gene
- if oestrogen acts on a gene that controls cell division and growth it will be activated
- can produce a tumour
What can oestrogen cause
Breast cancer
Define genome
The complete set of genes in a cell including those in mitochondria and or chloroplasts
What does WGS sequencing stand for
Whole genome shotgun sequencing
What is WGS sequencing
Researches cut the DNA into many small pieces, easily sequenced sections and then using computer algorithms to align overlapping segments to assemble the entire genome
What is WGS sequencing used for
Determining the complete DNA base sequence of an organism (its genome)
Give an example of medical advancements that have been made as a result of the human genome project
Over 1 million SNP’s have been found in the human genome which has advanced our understanding of diseases and disorders
What is an SNP
- single nucleotide polymorphism
- single base variations associated with disease and disorders
What is a proteome
All the proteins that can be coded for by the genome
What uses could the information gained from the human microbe project have
Provide knowledge if genes that can be exploited for example from organisms that can withstand extreme or toxic environments
Why is determining the proteome of prokaryotic organisms like bacteria relatively easy
- most prokaryotes have just one circular piece of DNA which is not associated with histones
- there are no introns (non coding parts of DNA0
What application does knowledge of the proteome project have
- identification of the proteins that act as antigens on the surface of human pathogens
- which can then be used in the production of vaccines
Why is determining the proteome of complex organisms difficult
- the genome contains many non-coding parts
- genome cannot directly be translated into proteome
- also everyone has different base sequences in their DNA, making it far more difficult
