7. Variations in DNA Flashcards
What effects can DNA mutations have?
- nonsense mutation
- missense mutation
- framshift mutation
what is a non sense mutation
premature termination of protein translation from nonsynonymous mutations
(stop codon)
What are non synonymous mutations
codon information is changed to another amino acid or stop
what are synonymous mutations
no change to codon information same amino acid is incoporated
what are missense mutations
incoporation of a different amino acid
- conservative substituition: exchange with amino acid of similar properties
- radical replacement exchange with amino acid of different properties
What are polymorphic mutations
acceptable variations to DNA sequence
what types of mutations are usually polymorphic
- synonymous/silent mutations
- intronic mutations
- intergenic mutations
What are copy number variations (CNVs)
large specifc regions of some chromosomes can be deleted/amplified (thus gene dosage) without any obvious ill effects.
- resulting variation in gene dosage os CNVs
what are potential phenotypic consequences of DNA mutations
- lethal mutation
- conditional mutation loss of function mutation
- loss of function mutation
- null mutation gain of function mutation
How does DNA slippage occur
highly repetitive streches of DNA sequence (often non-protein coding regions) can be problematic for DNApol
- slipping causes the deletion or insertion of nucleotides
which nitrogenous base mutations are most frequent
C to T
- occur disproportionally on X chromsome due to cytosine mediated X-inactivation
- responsible for many X linked disorders
Guanine and Adenine deamination is very rare and ledas to?
non-Watson& crick base pairing during DNA replication
What happens if depurination occurs (removal of purine base)
- normally recognized and repaired when in double stranded DNA by cellular repair mechanisms
- if present in single stranded can lead to mutation
- catalyzed by nitrous acid
Is depyrimidnation or depurination more frequent
depurination
What is the effect of high energy ionizing radiation (Xray &gamma rays)
- formation of free radical species
- direct interaction with DNA
What is the effect of non-ionizing radiation (UV light)
- DNA bases efficiently absorb UV
- abdorb energy to promote electrons
- exited pyrimidines form covalent bonds (form pyrimidine dimers)
- pyrimidine dimers are mutagenic (repaired incorrectly
What can base pair analogs/intercaltors do?
can squeeze between genuine base pairs of DNA causing distortions
What do alkylating agents do
electrophilic chemicals that add alkyl groups to various positions of DNA bases
- inhibit DNA helicase
- can cause indirect mutagenises if replaced incorrectly
Where are Reactive Oxygen Species derived from
ROS derive from both endogenous and exogenous sources
What does ROS do to DNA
cause oxidative damage by breaking base/nucleotide destruction and modification
Where do mispaired nucleotides that cause structional distortions come from
- inappropriate H bonding (wrong pairing)
- base analogs
- chemically modified bases
How are parental and template and newly synthesized DNA strands be determined in prokaryotes?
DNA hemi methaltion
How can DNA hemi methylation determine parental and newly synthesized DNA strand
specific A and C nucleotides are methylated at palindromic sequences
- (immidiately after replication they exist as hemi methylated state
How does nucleotide existion repair work
removal of bulky DNA lesions
- structural distorions in DNA detected and endonuclease enzymes cut DNA a
- oglionucleotide containing the mutation is then removed leaving a relatively large gap
- gap is filled with DNApol I
