L21- DNA/ chromosomal mutations Flashcards
mutagenesis
the process of mutation generation
a mutation is
a change of the nucleotide sequence, which can either have no affect on protein structure, or can render a protein changed
mutations arise
spontaenously due to mutagens
spontaneous mutations e.g.
deamination mutations
example of deamination
changes Cytosine to Uracil
e.g. can change 5-methylcytosine to thymine
types of mutagens
exogenous
endogenous
endogennous
DNA replication defects
exogenous
- ionsing radiation
- free radical
- mutagenic chemicals e.g. nitrites
- anti cancer agents
Defective or error prone DNA repair leads to
mutation
mutations may or may not
cause phenotypic cahnge
mutations can be
good or bad
- source of genomic variation
- driving force of evolution
- may cause disease
in transcription …
- DNA is read ……..
- mRNA is synthesised ……
- DNA is read 3’ to 5’
- mRNA is synthesised 5’ to 3’
In translation….
- mRNA is read…….
- polypeptide synthesis……
- mRNA is read 5’ to 3’
- polypeptide synthesis N to C
types of mutations
small scale (micro)
large scale (macro)
small scale mutations (3)
- substitution
- deletion
- insertion
large scale mutations (macro)
- abnormal number of chromosomes
- structural abnormalities
Abnormal number of chromosomes e.g.
- aneuploidy
- polypoloidy
structural abnormalities (4)
- deletions
- duplication
- inversion
- translocation
a transposable element (transposome)
is a DNA sequence that can change position within a genome- creating or reversing mutations
transposable elements are what sort of source of mutagenesis
endogenous
DNA sequences of transposable elements
- supernumerary (many copies)
- specific
- always contain within other DNA molecule
- moves as a discrete unit
- moves to random sites
transposable elements insertionally
inactivate genes or change gene expression
TEs can insert (jump into) a gene to
inactivate it
TE can jump out of a gene to
reactivate it
TE and the size of the gene
The bigger the gene the more likely it will be inactivated
e.g. Hb gene very small- unlikely
TE can also jump into
regulatory regions- affecting DNA expression
cartoon of transpostion
small scale mutations are synonymois with
single nucleotide polymorphism (SNP)
types of SNP
- Indels
- substitution of a single. few nucleotides within a gene
Indels
deletion or insertion mutations
deletion
nucleotide is removed from DNA
Insertion
nucleotide is inserted into DNA
INDELs can cause
frameshift mutations
If a multiple of three nucleotides are removed
- non frameshift mutation ( change in polypeptide length)
Reading frame displaced an entire codon- remaining amino acids unchanged- similar resulting protein
If one nucleotide is added or removed
- frameshift mutation
Resulting protein abnormally long or short, with random amino acids
Most likely unfunctional
substitution mutation
one nucleotide is replaced by another
substitution mutations may result in
silent mutations (synonynous)
missense jutation
nonsense mutations
synonymous (silent) mutations
same amino acid- degenerative genetic code
missense mutation
mutation codes for a different amino acid
- depends where the mutations occurs:
- can result in functional protein
- can result in non-functional protein
nonsense mutation
stop codon
- most deleterious
transition mutation (substitution mutation)
substition of the same base type
e.g. purine to purine
transversion (substitution)
change to diff type of base
i.e. pyrimidines to purine
pyrimidines
urine
cytosine
thymine
purines
guanine
adenine
example of single nucleotide polymorphism disease (SNP)
sicke cell mutation
sicke cell mutation
- Mutation in codon 7 of HBB gene
- Base substitution mutation (missense)
- One amino acid changed (6th aa- first is start codon)
SNP mutatons within regulatory sequences
- Alter. Promotor activity
- Alter translation initiation at AUG
- Prevent mRNA splicing
- Reduce mRNA stability
structural abnormalities
Movement of sections of chromosome
- deletion
- duplication
- inversion
- translocation
abnormal number of chromosomes occur due to
errors in gamete formation e.g. nondijunction
deletion
part of the gene is missing
duplication
part of the chromosome is duplicated
inversion
part of the chromosome breaks of and reattaches
translocation
parts of the chromosome are switched
Robertsonian translocation
- P arms detach from two chromosomes and are discarded
- Both Q arms from the chromosomes fuse
individuals with robertsonian translocation only have
45 chromosomes
aneuploidy
loss or gain of whole chromosome due to non-disjunction disorders
e.g. trisomyn and monosomy
trisomy
additional chromosome e.g. downsyndrome
monosomy
missing chromosome e.g. Turners syndrome
polyploidy
- Increased number of chromosomes per set
- E.g. Gain of haploid set of chromosomes (3n=69)
most common cause of polyploidy
polyspermy
triploidy occurs in how many oregnanacies and is the ause of how many miscarriages
2-3%
15% of miscarriages
moscaicism
Presence of two or more cell lines in an individual (throughout the body or tissue- specific)
Caused by non-disjunction in mitosis
detecting mutatiosn in chromosome suses
cytogenetic testing
name 4 cytogenetic tests
E.g. karyotyping (old fashioned)
E.g. Fluorescent in situ hydrbidsaiton (FISH)
E.g. microarray hydbridation
E.g. DNA sequencing
why is cytogenetic testing important
- accurate diagnosis and prognosis of clinical problems
- better clinical management
- assess future reproductive risk
- prenatal diagnosis
who should be refereed to cyrtogenetic testing
Prenatal diagnosis
Birth defects
Abnormal sexual development
Infertility
Recurrent fetal loss
Leukaemia
Solid tumours
Prognostic info for specific translocations
balanced mutations
no genetic info is lost or no phenotypic changes are apparent
unbalanced mutatuons
Anything that’s not balanced = unbalanced
◦E.g. loss of genetic info or gain of genetic info
◦Chain in phenotype
