22 - DNA MUTATIONS Flashcards
what are the different scales of mutations (chromosomal, insertional, point)
what are the different types of base substitution point mutations
what are indels
additions or deletions
what are synonymous mutations
also called silent
change sequence but not the AA
what are nonsynonymous mutations
what are nonsense mutations
what are frameshift mutations
how is a point mutation categorized when it has no effect on gene function
wild type function
what is a loss of function point mutation?
what is a gain of function point mutation?
what is an example of a loss of function mutation that leads to human disease
what is an example of a gain of function mutation that leads to human disease
what are examples of point mutations with a neutral or positive effect
what can mutations in non coding regions disrupt
how can point mutations alter mRNA splicing
what is an example of a synonymous mutation causing a loss of function of a gene
this is quite rare
a kidney cancer patient with mutation in PBRM1 gene had a much worse outcome than other kidney cancer patients without this mutation
this led to the loss of function of BAP1 due to the fact that the exon 11 was skipped, which introduced an incomplete protein
northern vs western blot reminder
what do the different types of mutations lead to in a western/northern blot
what are spontaneous vs induced mutations
what are the origins of spontaneous mutations
how do spontaneous errors during in DNA replication lead to mutations
what is strand slippage and what does it lead to
how do trinucleotide repeat disorders arise
what is an example of such trinucleotide repeat diseases
expanded CAG tracts, which codes for glutamine (Q)
known as polyQ diseases
expanded polyQ tracts lead to abnormal folding, which leads to protein aggregation and neural degeneration
example of a disease caused by trinucleotide repeat expansion in non coding regions
how is huntington’s disease caused by trinucleotide repeat expansion
trinucleotide expansion in the coding region of the HTT gene
the symptoms get worse throughout the generations, autosomal dominant, because each generation carries more expansion
concept of greater n (number of repeats) leads to greater slippage
what is depurination
spontaneous chemical change
what can spontaneous deamination of a base lead to
what are mutagens
by which mechanisms do mutagens induce mutations
what are intercalating agents and how do they work
how does UV light cause mutations/damage
causes T-T dimers
how does ionizing radiation cause mutations/damage
what is the Ames test and what question does it answer
How do we know if something is a mutagen?
pictures of the Ames test experiment how it is done
put a potentially mutagenic compound in the middle and let it spread out so that it creates a concentration gradient
what is the problem with the Ames test for humans/higher organisms?
when we ingest mutagenic compounds, they need to be digested and broken down first, and therefore might become something else once metabolized and work differently/not work anymore
what is the revised Ames test
Liver enzymes are added to test chemicals that might become mutagenic once metabolized
conducted with two different Salmonella strains to improve the detection of a broader range of mutagenic compounds. Each strain has specific mutations that make it sensitive to different types of DNA damage
