sl mutation and gene editing Flashcards
Gene mutations as structural changes to genes at the molecular level
- Distinguish between substitutions, insertions and deletions.
- A gene mutation is a permanent, random and structural change in the base sequence of the DNA.
- Point mutations (base substitution mutations)
Frameshift mutations (Deletions, insertions)
Consequences of base substitutions
- Students should understand that single-nucleotide polymorphisms (SNPs) are the result of base substitution mutations and that because of the degeneracy of the genetic code they may or may not
change a single amino acid in a polypeptide.
- A change to a triplet in the DNA, which causes a changed codon in the mRNA. In a silent mutation this has no effect on the protein sequence due to the degeneracy of the genetic code.
- In a missense mutation, the substitution can cause the expression of a different amino acid leaving the polypeptide either functional or dysfunctional, depending on the type of amino acid.
- In a nonsense mutation a shortened polypeptide is caused because the substituted base is a stop codon. The polypeptide may then result to be functional or dysfunctional.
random: A point mutation in the HOX gene of the fruit fly Drosophila melanogaster causes legs to sprout on their foreheads instead of antennae.
SICKLE CELL AMENIA
Consequences of insertions and deletions
- Include the likelihood of polypeptides ceasing to function, either through frameshift changes or through major insertions or deletions.
- Use trinucleotide repeats of the gene HTT as an example of insertion and the delta 32 mutation of the CCR5 gene as an example of deletion.
- In frameshift mutations involving insertions or deletions the entire reading frame (the entire gene sequence) is changed, often resulting in a polypeptide ceasing to function completely.
- All codons following the mutation are altered
Consequences of insertions and deletions
- Use the delta 32 mutation of the CCR5 gene as an example of deletion.
- CCR5 is a receptor protein found on the cells surface of white blood cells. The CCR5 gene that encodes the protein is located on chromosome 3. Some populations have inherited a frameshift mutation called Delta 32, resulting in a deletion of a portion of the CCR5 gene.
- Since the HIV-1 virus binds to the CCR5 receptor of white blood cells, homozygous carriers of this mutation are resistant to HIV infections.
Consequences of insertions and deletions
- trinucleotide repeats of the gene HTT as an example of insertion
- Huntington’s disease is a neurodegenerative genetic disorder, in which the HTT gene on chromosome 4 coding for the Huntingtin protein experiences a frameshift insertion mutation. The normal huntingtin gene has several repeat units of CAG, while the mutated one would shows one or several insertions of additional CAG sequences. The faulty protein results in neuronal degeneration in the brain, and eventually death due to neurological dysfunctions.
Causes of gene mutation
- Students should understand that gene mutation can be caused by mutagens and by errors in DNA replication or repair.
- Include examples of chemical mutagens and mutagenic forms of radiation.
- A mutation is a random change to the base sequence of a gene caused by errors in DNA repair or replication and mutagens. Mutagens can also be carcinogens resulting in uncontrolled cell division and tumor formation.
- Examples of mutagens: UV radiation, asbestos, cadmium compounds, PVC, diesel exhaust, benzene, tobacco smoke, gamma rays, alpha particles…
Causes of gene mutation - radiation
Radiation increases the mutation rate if it has enough energy to cause chemical changes in DNA. The higher the frequency (the shorter the wavelength), the more dangerous the radiation for human tissue becomes. Gamma rays and alpha particles from radioactive isotopes, short wave UV radiation and X-rays are all mutagenic.
Randomness in mutation
- Students should understand that mutations can occur anywhere in the base sequences of a genome, although some bases have a higher probability of mutating than others.
- They should also understand that no natural mechanism is known for making a deliberate change to a particular base with the purpose of changing a trait.
Consequences of mutation in germ cells and somatic cells
- Include inheritance of mutated genes in germ cells and cancer in somatic cells.
- If a mutation occurs in a gene/allele a germ cell (giving rise to gametes) the mutation can be inherited and would occur in all body cells and show in the entire organism.
- A mutation in somatic (body) cells have limited consequences; mutations like carcinogens, can cause a specific body cell to develop a malignant tumour
Mutation as a source of genetic variation
- Students should appreciate that gene mutation is the original source of all genetic variation.
- Although most mutations are either harmful or neutral for an individual organism, in a species they are in the long
term essential for evolution by natural selection.
- Gene mutations are the original source of all genetic variation. Although most mutations are either harmful or neutral for an individual organism, in a species they are essential for evolution by natural selection and without it the variation in a population would decline.
- A gene consists of a length of DNA with a base sequence that can be hundreds or thousands of bases long.
- An allele is a variant of a gene, differing in one or more bases from other alleles of a gene.
SNPssss
- A SNP is a type of allele but shows only a difference in one nucleotide. SNPs can be found in the coding and non-coding region of the DNA. Both types of variations are consequences of mutations.
- Several SNPs can be present in a gene, and due to the degeneracy of the genetic code they may or may not change the amino acid sequence in a polypeptide.
