D1.3 Mutation and Gene Editing Flashcards
Define Mutation
a mutation = a change in the base sequence of DNA, which can occur spontaneously or due to external factors
- Mutations can be corrected by cellular mechanisms, but if they are not repaired, they can become permanent and passed on during cell division
- Mutations can lead to variations in phenotypes, potentially affecting protein function and cellular processes
Distinguish between Base Substitution, Insertion, and Deletion Mutations
Base Substitution:
- One base is replaced by another in the DNA sequence.
- Can be caused by chemical changes or DNA mispairing
- Can result in silent, missense, or nonsense mutations
Insertion:
- A nucleotide is added into the DNA sequence, increasing the length of the gene.
- This is a more significant change, as it requires a break in the sugar-phosphate backbone of DNA.
- Can cause a frameshift mutation, which alters the reading frame of the codons and potentially changes the entire protein sequence.
Deletion:
- A nucleotide is removed from the DNA sequence, shortening the gene.
- Requires two breaks in the DNA backbone.
- Like insertions, deletions can cause frameshift mutations, leading to drastic changes in the protein sequence.
- Multiple insertions or deletions can occur, affecting two or more consecutive nucleotides.
Define Single-Nucleotide Polymorphism (SNP)
Single-Nucleotide Polymorphism (SNP) = A variation at a single nucleotide position in the DNA sequence among individuals
- SNPs can occur in coding or non-coding regions of the genome.
- Most SNPs have no effect, but some are associated with diseases or genetic traits
- SNPs contribute to genetic diversity within a population
Compare the Impact of Base Substitution Mutation in Coding and Non-Coding Sequences of DNA
In Non-Coding DNA:
- Base substitutions in non-coding regions are less likely to affect the organism since these regions do not directly encode proteins.
- Mutations may affect gene regulation or be neutral with no observable effect.
In Coding DNA:
- Base substitutions in coding sequences can lead to changes in the amino acid sequence of proteins.
- This can alter protein function, potentially causing disease or altered traits.
- Mutations in coding regions are more likely to have a noticeable effect on the phenotype.
Outline the Impact of Genetic Code Degeneracy on the Effect of Mutations
Genetic Code Degeneracy = The redundancy in the genetic code where multiple codons can code for the same amino acid.
Impact on Mutations:
- Same-sense mutations (silent mutations) often do not affect the phenotype because the new codon codes for the same amino acid.
- Redundancy minimizes the impact of mutations in some cases, as a mutation may not change the protein’s structure or function.
–> This helps to cushion the potential harmful effects of mutations, making some mutations neutral.
Distinguish between Same-Sense, Nonsense, and Mis-Sense Base Substitution Mutations
Same-Sense Mutation (Silent Mutation):
- A base substitution that changes a codon to another codon for the same amino acid (ex. AGC to AGT, both code for serine).
- Typically no effect on the phenotype.
Nonsense Mutation:
- A base substitution that changes a codon into a stop codon
- Premature termination of translation results in a truncated protein, usually non-functional
Mis-Sense Mutation:
- A base substitution that changes one amino acid in the protein sequence.
- Depending on the amino acid’s properties and position, this may have a minimal or severe effect.
- Can cause genetic diseases (like sickle cell anemia)
Define “Frameshift” Mutation
Frameshift Mutation = a mutation caused by insertions or deletions of nucleotides that alters the reading frame of the gene.
- These mutations shift the way codons are read during translation, often resulting in completely altered protein sequences.
- Insertions and deletions that are not in multiples of three nucleotides will change the reading frame for all codons downstream of the mutation.
–> This can lead to severe functional disruptions in the resulting polypeptide, often rendering the protein nonfunctional.
Outline the Consequences of Insertions and Deletions on Polypeptide Structure and Function
- Major Insertions or Deletions
- Minor Insertions or Deletions (1-2 nucleotides
- Insertions/Deletions in Multiples of Three Nucleotides
- Example (BRCA1 Gene Mutation)
Major Insertions or Deletions:
- Almost always result in nonfunctional polypeptides due to the disruption of the reading frame
- Significant changes in amino acid sequence, potentially leading to loss of function
Minor Insertions or Deletions (1-2 nucleotides):
- Can still cause frameshift mutations, completely altering the protein structure and function
- Total loss of function in the polypeptide is likely
Insertions/Deletions in Multiples of Three Nucleotides:
- Do not cause frameshift mutations but may result in one or more extra or missing amino acids
–> can lead to radical structural changes in the protein, affecting its ability to perform its function
Example (BRCA1 Gene Mutation):
Mutations in the BRCA1 gene can disrupt its DNA repair function, leading to an increased risk of tumors and cancer
Outline Causes of Gene Mutation (3)
1. Spontaneous Mutations:
- Occur naturally, but are rare due to DNA’s resistance to chemical change.
2. DNA Replication Errors:
- During DNA replication, base-pairing errors can sometimes occur and go uncorrected by DNA repair mechanisms, leading to mutations.
3. Mutagens:
- The chance of mutation is increased when mutagens are present.
Define Mutagen
Mutagen = Any external agent that increases the mutation rate by causing chemical changes in DNA
types of mutagens? (2)
1. Radiation:
- Includes gamma rays, X-rays, and alpha particles from radioactive elements.
- Ultraviolet radiation from sunlight can also be mutagenic.
2. Chemicals:
- Substances like polycyclic aromatic hydrocarbons, nitrosamines, and mustard gas are mutagenic.
Discuss the Impact of Randomness of Gene Mutations (3)
- Because mutations are unpredictable and occur by chance, they cannot be directed by organisms to achieve a specific outcome
- They have no influence on probability
–> The consequences of a mutation do not affect the likelihood of the mutation occurring (it’s random + unaffected by the result of the mutation) - Mutations Are Unlikely to Be Beneficial
–> Since they are random, they are typically neutral or harmful
No _____ is Known for Making a _____ to a DNA Sequence.
No Natural Mechanism is Known for Making a Deliberate Change to a DNA Sequence
(No natural mechanism exists in living organisms to intentionally change a specific DNA base to create a beneficial trait or change, it’s IMPOSSIBLE)
Distinguish between Germ Cells and Somatic Cells
Germ Cells:
- Germ cells give rise to gametes (sperm and eggs)
- Mutations in germ cells can be passed to offspring and affect future generations
- Located in the gonads (testes and ovaries)
Somatic Cells:
- Somatic cells are all the body cells except gametes
- Mutations in somatic cells are not inherited
- Changes in somatic cells do not affect offspring but can affect the individual
Compare the Consequences of a Germ Cell versus Somatic Cell Mutation
Germ Cell Mutations:
- Mutations can be inherited by offspring
- May lead to a new allele that can confer a genetic disease or, rarely, provide a benefit to the offspring
- Important to minimize mutations in gamete-producing cells to reduce genetic diseases
Somatic Cell Mutations:
- Mutations are not inherited
- Limited consequences because the mutated cell is replaced when it dies
- Mutations in genes controlling the cell cycle can lead to cancer due to uncontrolled cell division
