Gene Mutation and DNA Repair

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Questions and Answers

What type of mutation accounts for 30% of human disease-causing mutations?

Missense mutation

Nonsense mutation (correct)

Frameshift mutation

Deletion mutation

Which of the following best describes missense mutations?

They alter the amino acid sequence of a protein. (correct)

They create internal nonsense codons.

They lead to no change in the protein sequence.

They trigger rapid decay of mRNA.

Which characteristic is not associated with β-thalassemia?

Jaundice

Weakness

Increased hemoglobin synthesis (correct)

Frequent blood transfusions

What effect do base analogs have during nucleic acid biosynthesis?

They substitute for purines or pyrimidines. Signup and view all the answers

What gene is primarily affected by mutations causing β-thalassemia?

HBB gene Signup and view all the answers

Which of the following describes the impact of UV rays on DNA?

They create pyrimidine dimers that distort DNA conformation. Signup and view all the answers

How do nonsense mutations affect mRNA?

They trigger rapid decay of mRNA. Signup and view all the answers

What type of mutation is primarily caused by intercalating agents?

Frame-shift mutations Signup and view all the answers

Which of the following populations is most affected by β-thalassemia?

Mediterranean and North African populations Signup and view all the answers

How do alkylating agents contribute to mutations?

By donating alkyl groups that alter base pairing affinities. Signup and view all the answers

What type of mutation is associated with a single base-pair change in human genes?

Single-gene mutations Signup and view all the answers

Which type of mutation alters the protein sequence and leads to the creation of internal nonsense codons?

Frameshift mutation Signup and view all the answers

Which type of radiation transforms stable molecules into free radicals?

Ionizing radiation Signup and view all the answers

What is a common consequence of mutations in the HBB gene?

Decreased transcription efficiency of mRNA Signup and view all the answers

What is a consequence of pyrimidine dimers formed by UV rays?

They interfere with normal replication and repair. Signup and view all the answers

What type of mutation does not result in a change in the protein it encodes?

Silent mutation Signup and view all the answers

What type of mutation introduces a stop codon into the protein coding sequence?

Nonsense mutation Signup and view all the answers

Which mutation results in a codon that codes for a different amino acid?

Missense mutation Signup and view all the answers

What is a characteristic of a frameshift mutation?

It alters all subsequent codons from the point of mutation. Signup and view all the answers

What defines a null mutation?

A complete loss of function of the gene product. Signup and view all the answers

Which type of mutation occurs when a purine replaces a pyrimidine?

Transversion mutation Signup and view all the answers

Where can one explore comprehensive information on human genes and mutations?

OMIM - Online Mendelian Inheritance in Man database Signup and view all the answers

What is the effect of a gain-of-function mutation?

It results in enhanced, negative, or new functions. Signup and view all the answers

Which type of mutation would likely cause genetic diseases due to its effects?

Loss-of-function mutation Signup and view all the answers

Study Notes

Gene Mutation, DNA Repair, and Transposition

Topic: Gene mutation, DNA repair, and transposition were discussed.
Central Dogma of Molecular Biology: DNA undergoes transcription to mRNA, which then undergoes translation by ribosomes to create proteins within cells.

Gene Mutation Classification

Mutation: Any base pair change in DNA alters the nucleotide sequence of an organism's genome. This can occur in somatic cells or germ cells, influencing genetic diversity and evolution.

Classification Based on Molecular Change

Point Mutation (or Base Substitution): A change of one base pair to another in a DNA molecule.
- Missense Mutation: A nucleotide change within a protein-coding triplet, resulting in a different amino acid.
- Nonsense Mutation: A triplet is changed into a stop codon, leading to protein termination.
- Silent Mutation: A point mutation alters a codon but does not affect the amino acid at that position.
- Neutral Mutation: Mutation occurring in non-coding DNA, with no effect on gene products or expression.

Other Types of Point Mutation

Transition: A pyrimidine replaces a pyrimidine or a purine replaces a purine.
Transversion: A purine replaces a pyrimidine or vice versa.

Classification Based on Molecular Change: Frameshift Mutation

Frameshift Mutation: Insertion or deletion of one or more nucleotides within a gene.
- Result: Change in subsequent three-letter codons. May lead to a stop codon, halting polypeptide synthesis.

Classification Based on Effect on Function

Loss-of-Function Mutation: Reduces or eliminates the function of the gene product.
Null Mutation: Complete loss of function.
Gain-of-Function Mutation: Codes for a gene product with enhanced or novel functions.
Suppressor Mutation: A second mutation that reverses or relieves the effects of a previous mutation.
- Intragenic: Suppressor mutation occurs within the same gene.
- Intergenic: Suppressor mutation occurs in a different gene.

Classification Based on Phenotype

Phenotypic effect classifications: Visible, Nutritional, Biochemical, Behavioral, Regulatory, Lethal, and Conditional.
Examples provided for each classification (ranging from Mendel's peas to specific human diseases and animal traits).
Example of conditional mutation: Shown in Himalayan rabbits.

Mutations Occur Spontaneously and Randomly

Spontaneous Mutation: Changes in nucleotide sequence occurring naturally, not associated with specific agents.
- Example: DNA replication.

Mutation Rate

Rate of spontaneous mutation is typically low but varies between organisms and even between genes within the same species.

Spontaneous Mutations Arise from Replication Errors

DNA Replication Errors: DNA polymerase may insert incorrect nucleotides during replication. It has 3’ to 5’ exonuclease activity which allows for proofreading.
Tautomers: Bases that increase the chance of mispairing during DNA replication.

Spontaneous Mutations (Examples)

Depurination: Loss of a nitrogenous base in DNA, commonly guanine or adenine.
Deamination: Conversion of an amino group to a keto group, with cytosine converted to uracil and adenine to hypoxanthine.
Oxidative Damage: Reactive oxygen species (free radicals) that create DNA chemical modifications and sometimes damage.
Jumping Genes (Transposable Elements): These elements can cause mutations when moving within a genome.

Induced Mutations

Induced Mutation: Resulting from exogenous (external) factors such as UV radiation (example given of skin cancer).

Examples of Induced Mutations

Base Analogs
Alkylating Agents
Intercalating Agents
Adduct-Forming Agents
Ultraviolet (UV) Rays
Ionizing Radiation

Single-Gene Mutation and Human Diseases

Monogenic Diseases: Diseases caused by mutations in a single gene.
OMIM (Online Mendelian Inheritance in Man): A database of human genes, mutations, and disorders.

Single-Gene Mutation and Diseases: Point Mutations

Point Mutations: Mutations involving specific nucleotide changes, including missense and nonsense mutations
Missense; results in aa substitution.
Nonsense; a stop codon substitutes for an aa.
Frameshift; Involves deletions or insertions of nucleotides that alter the sequence's reading frame.

Single-Gene Mutation and Diseases: Other Types

Beta-thalassemia: caused by mutations in the beta-globin gene and can result in a decrease in red blood cells and oxygen delivery to the body.

Expandable DNA Repeats

Expansion of trinucleotide repeats in some mutant genes.
Disorders linked to trinucleotide repeat expansion: Fragile X syndrome, Myotonic dystrophy, and Huntington's disease
Trinucleotide Repeat Expansios: Causes conditions like intellectual disability and muscle/neurological problems.

DNA Repair Systems

Living systems have evolved sophisticated repair systems to counteract spontaneous and induced DNA damage, ensuring genetic integrity.
Mentioned scientists who received Nobel Prizes for their work on DNA replication and repair.

Proofreading and Mismatch Repair

DNA polymerase's proofreading capability (3' to 5' exonuclease) catches many errors.
Mismatch Repair (MMR) mechanism deals with errors that occur after proofreading.

Postreplication Repair

Repair system for DNA damage that has escaped earlier repair steps.
Role of RecA protein: Directs recombinational exchange to repair gaps.

Photoreactivation Repair

UV-induced damage can be repaired by visible light using photoreactivation enzymes.
Thymine dimers: Cross-links caused by UV radiation, disrupted by photoreactivation enzymes which require activation by blue light.

Base and Nucleotide Excision Repair

DNA repair system to correct damaged or inappropriate bases, involving enzymes to recognize damage sites and remove them.

Xeroderma Pigmentosa (XP)

Recessive genetic disorder affecting NER pathways. Increased sensitivity to UV radiation; often leading to skin cancer.

Ames Test

Assay used to determine a chemical compound's mutagenicity. It measures a compound's ability to cause mutations in bacteria.

Transposable Elements (TEs)

DNA sequences that move within or between chromosomes.
Types of transposable elements: DNA transposons and retrotransposons.
Potential to cause mutations if the movement disrupts genes.

Retrotransposons

A type of TE that expands itself by copying its contents via RNA intermediate, and then inserting that RNA back into the genome as DNA.
These are not infectious as they don't have other necessary structural components like a retrovirus.

End of Lecture

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Description

Explore the fascinating concepts of gene mutation, DNA repair mechanisms, and transposition. This quiz covers the central dogma of molecular biology and various types of mutations such as point mutations, missense, nonsense, and silent mutations. Test your understanding of how these genetic changes impact evolution and protein synthesis.