DNA Repair and How Mutations Occur Flashcards
Which type of mutation does not result in a change in the amino acid sequence?
nonsense
deletion
missense
silent
silent
What are single gene disorders?
caused by mutation in one particular gene
What are chromosome disorders?
broad group
-anomalies in chromosome number may not be actual mutations, just difference in numbers of genes expressed
-rearrangements
-insertions
-deletions
What are multifactorial or complex disorders?
multiple gene variants, gene variant with environment interactions
-caused by a combined effect of numerous common, low impact variants that individually would not cause disease
What is expressivity of a disorder ?
the fact that there can be different expressions in individuals that have this disorder
What is penetrance of a disorder?
the amount of people in a family that have it
What does variant mean?
gives no indication of disease state, just a different form
-still arisen by the mutation process
What does SNV mean?
single nucleotide variant
What are the ways to describe the frequency of a variant?
novel, rare, or common
What are the way to describe the impact of a variant?
low or high impact
What are ways to describe pathogenicity of a variant?
benign, likely pathogenic, or pathogenic
What are spontaneous mutations?
mutations that arise naturally during DNA replication
What are induced mutations?
caused by radiation and chemicals
Where can mutations occur in the DNA?
anywhere in the nuclear or mitochondrial DNA
Where are mutations located that are most heavily studied?
mutations that affect the protein coding sequence of genes
Can mutation in the introns cause disease?
yes
What are some examples of non-coding DNA?
gene regulatory elements, introns, and repetitive elements
What are silent mutations?
SNVs that do not change the Amino acid sequence
What are nonsense mutations?
SNVs that cause premature stop codon
What are missense mutation?
SNVs that cause a different amino acid to be brought in
What are conservative mutations?
mutations that cause an incorrect amino acid to be brought in, but have a similar side chain so there is not that big of difference seen
What are nonconservative mutations?
mutations that cause an incorrect amino acid to be brought in, but have a different sized side chain so there can be a significant difference in folding and function
What are deletions?
deletion of a single or many nucleotides in a sequence
What are insertions?
insertion of a single or many nucleotides in a sequence
What are rearrangements?
When segments of DNA are moved around to place they are normally not at
What are frameshift mutation?
often involve deletion of insertion of a nonfactor of 3 number of nucleotides
-causes the reading frame to be shifted
What is an allele?
one of the two copies of a gene
What is homozygous?
if an individual has two copies of the same allele
What is heterozygous?
when an individual has one of each copies of an allele
What does it mean if something is dominant?
only need one copy to have a certain phenotype
What does it mean if something is recessive?
need two copies of the same allele to have that phenotype
What causes oxidative damage to DNA?
reactive oxygen species
What are the most common hydrolytic attack regions?
deamination and depurination
How much depurination occurs daily?
around 5000 purine bases are lost each day during depurination
How much deamination occurs daily?
around 100 pyrimadines lost each day during deamination
What are some things that can cause DNA damage?
-reactive metabolites
-exposure to chemicals in the environment
-UV radiation (can cause thymine dimers)
What percentage of Cytosine nucleotides are methylated in the genome?
around 3%
What do methylated cytosine do?
help to control gene expression
What is formed if the methyl group is removed from a cytosine?
thymine
*not removed by base excision repair
What helps to remove large regions of damaged DNA?
nucleotide excision repair
What removes a single nucleotide in a sequence of DNA?
base excision repair
What is homologous recombination?
natural process that occurs during meiosis
-base pairing between DNA strands and is used to facilitate genetic exchange between homologous chromosomes
what is non-homologous recombination?
does not add any base pairs to damaged DNA, just sticks the strands back together with a ligase
Is homologous recombination associated with single stranded or double stranded breaks?
both
What happens if you do not have/have mutation in repair proteins?
generally lethal
-or can lead to cancer
what type of diseases are caused by the combined effect of numerous common, low impact variants that individually would not cause disease but in combination they have the potential to do so?
multigenic or multifactoral diseases
what are the transitions mutations?
purine –> purine (A <–> G)
or
pyrimidine –> pyrimidine (C <–> T)
what are transversions mutations?
purine –> pyrimidine (A/G –> C/T)
or
pyrimidine –> purine (C/T –> A/G)
what kind of mutations causes Huntingtons and ALS?
repeat expression mutations
can silent mutations cause disease?
yes- can cause issues with splicing region
what type of mutation causes branchio-oto-renal (BOR) syndrome?
intronic variant impacting splicing
SNP’s are generally….
benign
why can cancer be difficult to treat?
the associated hyper-mutability
are mutations always bad?
no- a very low level of mutation accumulation is important for evolution
what is an AP site?
a location in DNA that has neither a purine or pyrimidine base
what does deamination cause?
DNA substitution (point mutation)
*one strand remains unchanged
what does depurination cause?
DNA deletion
*one strand remains unchanged
what happens when C is deaminated?
changed to U
when are mutations inherited?
in somatic tissue
in DNA of gametes
in DNA of gametes
