✅20 - Gene Expression Flashcards
What is a mutation?
Any change to the quantity or the structure of the DNA of an organism
What is a gene mutation?
Any change to one or more nucleotide bases or any rearrangement of the bases in DNA
What is substitution?
A nucleotide in a section of DNA is replaced by another nucleotide that has a different base
What are the three possible consequences for substitutions?
- The formation of a stop codon which leads to the end of the polypeptide chain
- The formation of a codon for a different amino acid, meaning that the structure of the polypeptide produced would differ and potentially be non functional
- The formation of a codon that produced the same amino acid, no change
What is deletion?
The loss of a nucleotide from the DNA sequence
What can deletion cause?
Frame shift to the left
What is addition?
An extra base becomes inserted into the sequence
What does addition cause?
Frame shift to the right
In what case will frame shift not occur with an addition mutation?
If three bases are added consecutively, to form a new codon
What is duplication?
One or more bases are repeated
What does duplication produce?
Frame shift to the right
What is inversion of bases?
A group of bases becomes separated from the DNA sequence and rejoin at the same position but the the inverse order
What is translocation?
A group of bases become separated from the DNA sequence on one chromosome and become inserted into the DNA sequence of a different chromosome
What effect can translocations have?
Significant effects on gene expression leading to an abnormal phenotype effecting the development of some types of cancer and reduced fertility
What can cause gene mutations?
They can be random, or caused by mutagenic agents
Typically how many mutations occur per generation in most species?
1 or 2 in every 100,000 genes
What are some mutagenic agents?
High energy ionising radiation
Chemicals
How can high energy ionising radiation act as a mutagenic agent?
They can disrupt the structure of DNA
How can chemicals act as mutagenic agents?
Chemicals such as nitrogen dioxide may directly alter the structure of DNA or interfere with transcription. Some chemicals in cigarette smoke can inactivate tumour suppressor genes
What are totipotent cells?
Ones which can differentiate into any type of body cell
In what ways can gene be ‘switched off’ in a cell?
By preventing transcription and so preventing the production of mRNA
By preventing translation
What are stem cells?
Undifferentiated dividing cells that occur in adult animal tissues and need to be constantly replaced
What are the sources of stem cells in mammals?
Embryonic stem cells
Umbilical cord blood stem cells
Placental stem cells
Adult stem cells
What are adult stem cells?
Found in the body tissues of the fetus through to the adult. Specific to a particular tissue or organ in which they produce the cells to maintain and repair tissues throughout the organisms life
What are the types of stem cells?
Totipotent stem cells
Pluripotent stem cells
Multipotent stem cells
Unipotent stem cells
What are totipotent stem cells?
Ones which can differentiate into any type of cell, including placental cells
What are pluripotent stem cells?
Ones which can differentiate into any type of body cell
What are multipotent stem cells?
Can differentiate into a limited number of specialised cells
What are unipotent cells?
Can only differentiate into a single type of cell
What are induced pluripotent stem (iPS) cells?
A type of pluripotent cell produced from unipotent stem cells
How are iPS cells created?
They are genetically altered to make them acquire the characteristics of an embryonic stem cell. Genes and transcriptional factors are induced to make this happen.
How do iPS cells differ from embryonic stem cells?
Although they express some of the same genes, they are not exact duplicates. iPS are capable of self renewal and so provide an infinite supply
How are pluripotent cells used in treating human disorders?
They can be used to regrow damaged tissues or replace missing ones
What are transcriptional factors?
A specific molecule that can move from the cytoplasm to the nucleus to switch on genes eg. oestrogen
How do transcriptional factors work?
They bind to a specific base sequence of the DNA and the binding causes the region of DNA to begin transcription
What happens when a gene is not being expressed?
The site which the transcriptional factor binds to is not active
How does oestrogen act as a transcriptional factor?
- It binds with a complementary receptor molecule of transcriptional factor in the cytoplasm
- Oestrogen changes the shape of the DNA binding site of the transcriptional factor, activating it
- The transcriptional factor can now bind with DNA and stimulate transcription of the particular gene
What is epigenetics?
Where environmental factors can cause heritable changes in gene function without changing the base sequence of DNA
What is the epigenome?
The chemical tags attached to the DNA which determines the shape of the DNA-histone complex
What is epigenetic silencing?
When genes are inactive in a tightly packed arrangement and therefore ensures that they cannot be read
Once attached to DNA, what effects to proteins have?
- acetylation of histones leading to the activation or inhibition of a gene
- methylation of DNA by attracting enzymes that can add or remove methyl groups
What makes DNA more accessible for transcription?
When the association of histones with DNA is weak, so the DNA-histone complex is less condensed
How is transcription inhibited?
When DNA is loosely wrapped around the histones
How does acetylation impact transcription?
Acetylation leads to a more loosely wrapped DNA-histone complex, so increases transcription
How does decreased acetylation lead to a decreased transcription?
Decreased acetylation increases the positive charges on histones and therefore increases their attraction to phosphate groups of DNA. Association between DNA and is stronger and DNA not accessible to transcription factors.
How does methylation affect transcription?
It inhibits transcription
Which bases are methyl groups added to in methylation?
Cytosine
How does methylation inhibit transcription?
- 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 can dieseases be treated with epigenetic therapy?
By using drugs that inhibit enzymes involved in histone acetylation or DNA methylation
In diagnostic tests that help detect levels of methylation or acetylation at an early stage of the disease
What is siRNA?
Small Interfering RNA
How can translation of a gene be inhibited?
By breaking down the mRNA before information coded for can be translated into a polypeptide
How is siRNA produced?
An enzyme cuts larger double-stranded molecules of RNA into smaller sections called siRNA
How does siRNA prevent gene expression?
- One of two siRNA strands combines with an enzyme
- The siRNA molecule guides the enzymes to an mRNA by pairing up its bases with the complementary ones on a section of mRNA
- The enzyme cuts the mRNA into smaller sections
- mRNA is no longer capable of being translated
- Gene not expressed
What is cancer?
A group of diseases caused by damage to the genes that regulate mitosis and the cell cycle, leading to unrestrained growth of cells
What are malignant tumours?
Cancerous ones
What are benign tumours?
Non-cancerous ones
What are the characteristics of malignant tumours?
- Can grow to a large size
- Grow rapidly
- Cell nucleus often appears large and dark due to DNA abundance
- Cells become de-differentiated
- Not surrounded by capsule and so grow finger-like projections into surrounding tissue
What is metastasis?
A tumour spreading to other regions of the body by forming secondary tumours
What are the characteristics of benign tumours?
- Can grow very large
- Grow very slowly
- Cell nucleus appears relatively normal
- Cells are well differentiated
- Surrounded by a capsule of dense tissue so remain as compact structure
Cancer cells are derived from…
…a single mutant cell
What can an initial mutation in a cell cause?
Uncontrolled mitosis
What are the two main types of genes that play a role in cancer?
Tumour suppressor genes and oncogenes
What are oncogenes?
Mutations of proto-oncogenes, which stimulate a cell to divide when growth factors attach to a protein receptor on its cell surface membrane, activating the gene that causes DNA to replicate and the cell to divide.
What can happen if a proto-oncogene mutates into an oncogene?
It can become permanently activated (switched on)
What are the two main reasons proto-oncogenes are permanently switched on if they mutate into an oncogene?
- 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
What are tumour suppressor genes?
Genes that slow down cell division, repair mistakes in DNA and signal to cells when to undergo apoptosis
What happens if a tumour suppressor gene mutates?
It is inactivated and stops inhibiting cell division so the cells are free to divide out of control
How can hypermethylation lead to cancer?
- Hypermethylation occurs in a specific (promoter) region of tumour suppressor genes
- This leads to the tumour suppressor gene being inactivated
- As a result transcription of the promoter region is inhibited
- Tumour suppressor gene therefore silenced
- Inactivation leads to increased cell division and formation of a tumour.
How can hypermethylation lead to breast cancer?
If the gene BRCA1 is hypermethylated, cell division is not controlled
How can oestrogen influence breast cancer?
Increased levels after menopause can increase risk of breast cancer because it can lead to the development of oncogenes from proto-oncogenes
What are the risk factors associated with cancer?
Smoking Diet Obesity Physical Activity Sunlight
What is bioinformatics?
The science of collecting and analysing complex biological data such as genetic codes
What is the whole-genome shotgun technique (WGS)?
Involves researchers cutting DNA into many small, easily sequenced sections and then using computer algorithms to align overlapping segments to assemble the entire genome
What are single nucleotide polymorphisms?
Single-base variations in the genome that are associated with disease and other disorders
What is the proteome?
All proteins produced in a given type of cell (cellular proteome) or organism (complete proteome) at a given time, under given conditions
Why can it be useful to determine the genome and proteome of bacteria?
Ones from organisms that can withstand extreme or toxic environmental conditions have potential uses in cleaning up pollutants or manufacturing biofules
Why is determining the proteome of prokaryotic organisms relatively easy?
- The vast majority of prokaryotes have just one, circular piece of DNA that is not associated with histones
- There are none of the non-coding portions of DNA that are typical of eukaryotes
How can knowledge of the proteome of prokaryotes be applied?
The identifications of proteins that act as antigens on the surface of pathogens mean that they can be used in vaccines
Why is determining the genome and proteome of larger organisms more complex?
The genome contains many non coding genes as well as others that have the role of regulating other genes, only around 1.5% of genes code for proetins. Every person’s DNA is also different, aside from identical twins
