TOPIC G: MUTATIONS AND CANCER Flashcards
What is a point mutation?
Point mutations refer to changes in one nucleotide pair of a gene. If a point mutation occurs in a gamete or cell that gives rise to gametes, it may be inherited by its offspring and to succession of future generations.
If the mutation has an adverse effect on the phenotype of an organism, mutant condition is referred to as a genetic disorder or hereditary disease.
What is substitution/addition/deletion mutations?
S: Substitution is the replacement of one nucleotide pair with another pair of nucleotides.
A: Insertion of one or more nucleotide pairs into a DNA sequence.
D: A deletion is a mutation in which one or more nucleotide pairs are removed from a DNA sequence.
What is a silent mutation?
Silent mutations are mutations that have no effect on amino acid sequence.
No observable effect on organism phenotype.
Some substitution mutations are silent due to the redundancy/ degeneracy of the genetic code.
What is a missense mutation?
Other substitutions may change an amino acid but have little effect on the protein because new amino acid may have properties similar to those of the amino acid it replaces.
Replacement amino acid may also be in a region where the exact sequence of amino acids is not essential to protein function.
Substitutions usually result in this. The altered codon still codes for an amino acids and make sense, but not necessarily the right sense.
What is a nonsense mutation?
A point mutation can also change a codon for an amino acid into a stop codon. It causes translation to be terminated permanently.
This nonsense mutation results in the polypeptide formed being shorter than the polypp encoded by the normal gene. Nearly all nonsense mutation leads to non-functional proteins.
What is a frameshift mutation?
Additions or deletions often have a disastrous effect on the resulting protein.
mRNA is read as a series of triplet nucleotides during translation, addition or deletion of nucleotide pair may alter the reading frame of the gene.
Frameshift occur whenever the number of nucleotides inserted or deleted is not a multiple of 3.
All the nucleotides that are downstream of the addition or deletion will be improperly grouped into codons, resulting in a extensive change in amino acid sequence.
Change in codons may result in premature termination.
Unless the mutation is near gene end, the protein produced will be non-functional.
What is sickle cell anemia?
Mutations-Symptoms.
Autosomal recessive disorder, substitution of a single nucleotide from CTT to CAT in DNA template strand of chromosome 11.
The original amino acid coded for is glutamate is changed to valine at the sixth position.
Glutamate and valine are amino acids with very different properties. Glutamate is hydrophilic and valine is hydrophobic.
Mutated haemoglobin tends to polymerise into long rigid chains when not bound to oxygen due to hydrophobic interactions between the hydrophobic regions on different Hb molecules. The long fibres distort the membrane of the red blood cells giving it its distinct sickle shape.
This results in the decreased oxygen-carrying ability of the red blood cells.
In individuals who are homozygous for the mutant allele, altered Hb results in the sickling of red blood cells and produces the multiple symptoms associated with sickle-cell disease, such as shortness of breath.
What is aneuploidy?
An organism possesses an extra chromosome or lacks a chromosome.
What is non-disjunction and its results?
A pair or pairs of HC/sister chromatids fail to separate during anaphase.
Gametes receive two of the same type of chromosome/extra chromosome.
Gamete with no copy of a particular chromosome type.
The zygote will have an extra chromosome or a missing chromosome.
Non-disjunction during anaphase 1 of meiosis results in all aberrant gametes.
Non disjunction during anaphase 2 results in half normal gametes and half aberrant gametes.
What is polyploidy?
Organism acquires more than two complete sets of chromosomes.
3n (tetraploids)
4n (quadraploids)
Triploidy may arise
What are the three checkpoints for mitotic cell cycle?
G1 - ensures where the cell size is adequate and there are sufficient nutrients available and growth factors present for cell to undergo mitosis.
G2 - ensures that cell size is adequate and semi-conservative DNA replication has been completed successfully.
Metaphase checkpoint ensures that all chromosomes are attached to spindle fibres.
What are proto-oncogenes?
(POG)
POG encode proteins that stimulate normal cell division. The Gain-Of-Function mutation of POG to oncogenes leads to increase in amount of POG protein product or permanently activated proteins.
This will result in uncontrolled cell division, leading to CANCER.
GOF mutation results in a dominant allele as the effect of the normal allele is masked by the mutated allele.
What are Tumour Surpressor Genes?
TSG
TSGs encode proteins that inhibit cell division or promote apoptosis.
The Loss-Of-Function mutation of TSGs to mutated tumour surpressor genes leads to no protein product or decrease in amount of protein product or permanently deactivated proteins. This will result in uncontrolled cell division, possibly leading to cancer.
LOF mutation results in a recessive allele as the normal dominant allele encodes functional protein. Two alleles of a gene need to be mutated to have an effect.
What occurs during the onset of cancer?
When the control of the cell cycle is defective cells divide uncontrollably.
Cancer cells exhibit a loss of anchorage dependence. Normal cells need to anchor to a surface before they can divide. Cancer cells are able to divide without a surface to anchor.
Cancer cells exhibit a lack of density dependent inhibition. Normals cells divide as a single layer and stop upon contacting another cell. Cancer cells continue to divide even after a layer of cells had been formed.
What are the causative factors of cancer?
Physical factors
Ionising radiation (causes formation of chemically active ions in the cells which are capable of damaging and breaking DNA.
UV light causes DNA to increase in energy level, causing damage to DNA double helix by creating kinks.
Chemical Factors (causes chemical changes in bases resulting in incorrect base pairing.
Biological (Viruses/Fungus)
Genetic Factors (Mutated genes like oncogenes or mutated TSGs found in parental gametes.
Loss of immunity.
