Gene Expression Flashcards
when do gene mutations arise?
during DNA replication
6 types of gene mutation
addition, deletion, substitution, inversion, duplication and
translocation of bases
what increases the mutation rate?
mutagenic agents
How are cells able to control their metabolic activities?
by regulating the transcription and translation of their
genome
genome
the complete set of genetic material present in a cell or organism
proteome
all of the proteins produced by a particular type of cell or organism at a given time.
What does control of translation allow for in multicellular organisms?
enables cells to have specialised
functions, forming tissues and organs
name some mutagenic agents
UV/ ionising radiation, chemicals like those in cigarette smoke, asbestos and some viruses
What is a substitution mutation?
one + bases is swapped for another
What is a deletion mutation?
1 + bases are removed
What is a addition mutation?
1 + bases are added
What is a duplication mutation?
1 + bases are repeated
What is a inversion mutation?
a sequence of bases is reversed
What is a translocation mutation? What is this the same as?
a sequence of bases is removed from one location in the genome to another, on the same chromosome or not.
- like a deletion from one chromosome and an addition to another.
Why might a substitution/ 2 base inversion mutation not affect the encoded amino acid sequence?
Because only 1 triplet code is affected. The changed codon could code for the insertion of the same amino acid because the genetic code is degenerate.
Which types of mutations usually affect the amino acid sequence?
addition, deletion, duplication
Why would an addition mutation affect the encoded amino acid sequence?
The number of bases in the DNA code changes, causing a frameshift to the right, so all the codons following the addition are read differently and will code for different amino acids.
4 types of stem cell
totipotent, pluripotent, multipotent, unipotent
Totipotent stem cells
can divide and produce any type of body cell. they occur for a limited time in early mammalian embryos.
How do totipotent cells become more specialised during development?
by transcribing only part of their DNA.
Pluripotent cells (3)
- found in embryos
- can differentiate into almost any cell type (not placenta cells)
- divide in unlimited numbers
Uses of pluripotent stem cells
treating human disorders such as leukaemia, potentially also alzheimer’s, heart damage and type 1 diabetes.
Multipotent stem cells
can differentiate into a limited number of types of specialised cells.
Where are unipotent and multipotent stem cells found?
mature mammals
Unipotent stem cells
can only divide and differentiate to form a single cell type
How are iPS cells produced
induced pluripotent stem cells - produced from adult somatic cells using appropriate protein transcription factors
*** see exam qu.
unipotent stem cells example
Formation of cardiomyocytes - cardiomyocytes are heart muscle cells. These cannot undergo cell division, but can be replaced with new cardiomyocytes which form from a small pool of unipotent stem cells found in the heart.
Regulation of transcription by transcriptional factors (4)
include how activator and inhibitor transriptional factors work.
- Transcription of target genes can be stimulated or inhibited when specific transcriptional factors move from the cytoplasm into the nucleus.
- Transcription factors have a binding site which binds to a specific DNA base sequence in the promoter region of a target gene.
- Activator transcriptional factors stimulate transcription, e.g. by helping RNA polymerase to bind. mRNA is produced and leaves the nucleus for translation to occur.
- Inhibitor transcriptional factors prevent transcription by binding to the promoter region and preventing RNA polymerase from binding, so transcription cannot occur.
How can oestrogen initiate transcription?
- Oestrogen is a steroid hormone which is lipid soluble, so can easily diffuse into cells through the phospholipid bilayer.
- Oestrogen can initiate transcription by combining with a receptor site on a transcriptional factor.
- This activates the transcriptional factor by causing the DNA binding site to change shape. The transcription factor can enter the nucleus, bind to DNA and stimulate transcription.
What is epigenetics?
changes in gene function and expression which can be inherited, without change to the DNA base sequence. This involves chemical tags on DNA and histone proteins which form the epigenome.
What is DNA in the nucleus associated with?
proteins called histones
Effects of increased DNA methylation
inhibits transcription:
- by preventing transcriptional factors from binding to DNA
- by attracting proteins which condense the DNA-histone complex, so DNA can’t be accessed by transcriptional factors.
what is DNA methylation?
the addition of a methyl group, CH3 to cytosine bases in DNA, inhibits transcription
What does condensation of the DNA-histone complex mean?
DNA is more strongly associated with histones so is less accessible to transcription factors and is expression is decreased.
What is histone acetylation/ deacetylation?
an acetyl group can be added to a histone protein. The removal of an acetyl group is called deacetylation.
effects of histone deacetylation
Decreased acetylation increases the positive charges on histones, increasing their attraction to negatively charged phosphate groups in DNA. Histones are more strongly attracted to DNA so DNA can’t be accessed by transcriptional factors, and mRNA production can’t be initiated - the gene is switched off.
How does RNA interference with siRNA work to control translation?
1) An enzyme cuts large, double-stranded RNA molecules into smaller sections, siRNA.
2) One of the two siRNA strands combines with an enzyme.
3) The siRNA guides the enzyme to an mRNA molecule by pairing up its bases with a complementary section of the mRNA.
4) When in position, the enzyme cuts the mRNA into smaller sections.
5) The mRNA can no longer be translated into a polypeptide.
6) The polypeptide cannot be produced, so gene expression has been blocked.
How is epigenetics involved with disease?
Epigenetic changes can also be responsible for some diseases by causing abnormal activation or silencing of genes.
How can epigenetic treatments for disease work?
to counteract the epigenetic changes that cause disease.
E.g. drugs that inhibit enzymes which produce the epigenome to reverse abnormal changes (e.g. switch genes on that have been abnormally silenced)
How can epigenetics be usedin diagnostic tests?
Diagnostic tests to detect the early stages of disease (like cancer/ alzheimer’s) - epigenetic changes can be identified before other noticeable symptoms, so people have a better chance of being treated or cured.
Main characteristics of benign tumours
grow more slowly, cells are surrounded by a fibrous capsule to remain together - do not metastasise. Cell nucleus appears normal, cells are often well-differentiated.
Main characteristics of malignant tumours (5)
grow rapidly, cells are able to spread to other regions of the ody via metastasis (so form secondary tumours). The cell nucleus often appears darker and cells become unspecialised. More frequent recurrence.
What is cancer?
a group of diseases caused by damage to the genes regulating mitosis and the cell cycle, which leads to uncontrolled cell division and the formation of tumours which constantly expand in size.
Role of oncogenes in the development of cancer
The mutation of a proto-oncogene into an oncogene so it becomes permanently activated and cell division is stimulated. The cell divides rapidly and out of control, so a tumour develops.
Role of tumour suppressor genes in the development of cancer
*** see exam qu.
Abnormal methylation of oncogenes - how can this lead to cancer?
Hypomethylation = reduced methylation.
If this occurs in the promoter region of oncogenes, it leads to their activation, rapid cell division and tumour formation.
Abnormal methylation of tumour suppressor genes - how can this lead to cancer?
- Hypermethylation of the promoter region of tumour suppressor genes leads to their inactivation.
- Transcriptional factors cannot bind to the promotor region and stimulate transcription, so the TS gene is switched off.
- TS genes normally decrease the rate off cell division, so this inactivation leads to an increase in cell division rate and the formation of a tumour.
Role of proto-oncogenes
stimulate cell division when specific growth factors attach to a protein receptor on the CSM. This leads to activation of genes that cause DNA replication and cell division.
Role of tumour suppressor genes normally
slow down cell division, repair mistakes in DNA and trigger programmed cell death - apoptosis. They have the opposite role to proto-oncogenes.
The role of oestrogen in the development off some breast cancers
- An increased concentration of oestrogen increases the risk of a woman developing breast cancer.
- Oestrogen activates genes by binding and activating a receptor which promotes transcription (transcriptional factor).
- If the gene which oestrogen acts on controls cell division and growth (e.g. proto-oncogene ⇒ oncogene), this gene will be activated and the rate of cell division will increase. This could produce a tumour.
Why is it harder to sequence the proteome from the genome of more complex organisms?
as non-coding DNA and regulatory genes are present.
What to genome projects aim to do?
sequence and read the genomes of many different organisms, including humans
What does determining the genome of simpler organisms allow for?
the sequneces of proteins that derive from the genetic code (the proteome) of the organism to be determined.
What is the application of determining the proteomes of simpler organisms (using genome projects)?
identifying potenial antigens for use in vaccine production.
how are genome sequencing methods changing?
they are continuously updated, becoming quicker, more cost effetcive and automated.
Explain how mice prevented their BGC falling when they had not eaten for 48 hrs
- release of glucagon
- leads to formation of glucose in liver cells
- from non-carbohydrates
