Lecture 2 - DNA Mutations And repair Flashcards
What are mutations?
Changes in DNA that may or may not affect the phenotype (looks, how gene is expressed)
What can random changes in an organisms DNA be caused by?
- It can be inherited (passed down from parent to offspring)
- Can be caused by carcinogens (cancer causing agents in the environment)
What are replication dependent or independent mutations
- Replication-dependent mutations - Errors that can occur during DNA replication
- Replication-independent mutations - Errors that also occur independently of DNA replication
Spontaneous mutations vs induced
Spontaneous - Mutations that occur as a result of natural changes in DNA
Induced - Changes caused by environmental chemicals and radiation
- Mutagen chemicals that increase the rate of mutations above the spontaneous
Environmental agents (mutagens)
- Physical - radiation
– heat
– UV
– Ionizing - Chemicals
– Natural toxins
– Synthetic substances
—> Laboratory substances
—> Pollutants
—> Chemoterapeutics
How many mutations does our DNA undergo during our lifetime and why?
- 30 New mutations
- Because of mistakes during DNA copying or cell division, but more often because of damage from the environment
What are hotspots? And are all sites equally susceptible to mutations?
- Hotspots are sites that gain more mutations than expected
- No, different sites are not equally susceptible to mutations
How does gender affect mutations?
- Male/female ration is ~6
- Higher mutability in human and mammalian males
What are Somatic mutations, where do they occur and how?
- Somatic mutations - Not inherited, don’t play a role in evolution
- Localized within cells of an organism (arise in Somatic cells)
- Passed on to other cells through mitosis
- Mosaicism: tumors, antibody diversity, etc..
- Higher in dividing cells
What are germ-line(Generative) mutations?
- Germ-line mutations - Inherited and thus are important in evolution
- Occur in cells that produce gametes
- Passed on to future generations
What kind of mutations are there?
There are two kinds:
- Chromosomal mutations
- Gene mutations
Mutation sizes and what they mean
- Large mutations - Genome mutations -> Change of chromosome number
- Medium mutations - Chromosome mutations -> Change of chromosome structure
- Small mutations - Gene mutations -> Ranging from change to a single nucleotide to a whole gene (not visible)
– Affecting the length of DNA:
—> Deletion (single base or shorter-longer sequences)
—> Insertion (single base or shorter-longer sequences- repetitive more insertions than deletions)
– No effect on the length of DNA (nucleotide substitution)
Neutral, Beneficial and Harmful mutations
- (Most) Neutral - During evolution later might be harmful or beneficial
- (Some) Beneficial:
– Harmful one mutates back to wild
– Getting beneficial function
—> Diversity of antibody
—> CCR5^32 - HIV resistance (^ = delta)
—> Sickle cell anemia - malaria resistance - (Some) Harmful - Causing diseases (all monogenic inherited diseases)
What are gain-of-function mutations and what do they do?
- They are mutations that change the gene production such that it gains a new and abnormal function
- Produce an entirely new trait
- Causes a trait to appear in inappropriate tissues or at inappropriate times in development
- Frequently dominant
What are loss-of-function mutations and what do they do?
- Gene product having less or no function
- Complete or partial loss of normal function
- Structure of protein so altered it no longer works correctly
- Can occur in a regulatory region that affects transcription, translation or splicing of the protein
- Frequently recessive
Back mutation or reversion and lethal mutations.
- Back mutation or reversion: A point mutation that restores the original sequence and hence the original phenotype
- Lethal mutations: Mutations that lead to the death of the organisms which carry the mutations
Phenotypes in back mutation or reversion and lethal mutation
- Most often recessive
– Exception, Haploid sufficiency - when the reduced dosage of a normal gene product is not enough for a normal phenotype - Dominant negative mutations
– In humans have been implicated in cancer (e.g. Mutations in genes p53, ATM)
Suppressor mutations
- Suppresses the effect of other mutation
- Occurs at the site different from the site of the original mutation
- An organism with a suppressor mutation is a double mutant but exhibits the phenotype of un mutated wild type
What are chromosomal mutations? What is a normal chromosome amount for humans? Example of a mutation
- Abnormal changes in the structure of all or part of a chromosome, OR in the number of chromosomes an organism has
- Normal humans have 46 chromosomes -> 23 pairs
- E.g. Down syndrome that has 47 chromosomes
What do we do and see during karyotyping?
- We take a sample of blood cells
- Chromosomes get separated out, viewed with a microscope and photographed
- The photograph gets rearranged to show the paired chromosomes
- Size, shape and banding pattern are used to pair the chromosomes
What are the different types of DNA damage?
- Mismatches - arise from occasional incorporation of incorrect nucleotides
- Abnormal bases - Arise from spontaneous deamination, chemical alkylation, or exposure to free radicals
- Pyrimidine dimers - Form when DNA is exposed to UV light
- Backbone lesions - occur from exposure to Ionizing radiation and free radicals
