MUTAGENESIS Flashcards
What makes up dna , describe it
chromosomes - chromatin - dna
carry genetic info
double helix
genetic code properties
- mrna read by codons
- degenerate
- each codes for a single amino acide
what is mutagenesis
a process by which genetic info of an organism is changed in a stable manner resulting in a mutation
- disease
+ evolution
what is mutation
a permanent and heritable change of a nucleotide sequence
how many classifications of mutations are there
6
cause
cell type
character
phenotypic expression
cellular localization
effect on function
phenotypic expression class of mutation
each gene 2 copies
dominant
recessive
cell type
germline ( heritable )
- e.g hemophilia a , located on x chromosome so men only have one copy mainly men have it . and b european royal family )
somatic ( cancer/aging)
cause
- DNA replication error
base sub - depurination
loss of a purine base ( a or g) - tautomerism ( incorrect base pairing)
reposition of hydrogen atom of a base - slipped strand mispairing
( insertion , deletion )
misalignment during replication - unequal crossing over
duplication , deletion - nondisjunction of chromosomes
aneuploidies
failure to seperate during cell cycle - retrotransposons
insertion mutagenesis ( factor V11 - hemophillia A . APC - Predispoistion to colon cancer
many of these can be fixed by checkpoints or immediately repeat
mutagenesis by retrotransposons
1 line more info on this
slipped strand mispairing
trinucleotide repeat expansion
huntingdons disease cause ?
what are induced mutations plus types
- caused by mutagens
mutagens - increases the frequency of mutations
1) physical
2) chemical
3) biological - insertion mutagenesis
viruses EBV , Rous sarcoma virus
physical mutagens 2 sources
- ionizing radiation
gamma , x rays
natural source : cosmic , solar radiation , external terrestial sources
artificial : medicine , radiation therapy , nuclear weapons CHERNOBYL , HIROSHIMA
dna breakage
direct effect - chromosomal break
indirect - formation of free radicals ( o2, OH )
- ultraviolet light ( 254-260)
direct - pyrimidine dimer ( stop rep )
indirect - formation of free radicals
these dimers can actually be repaired by NER . nucleotide excision repair .
but too much of NER causes xeriderna in pigmentosum
- increased sensitivity to uv light , skin discolouration , tumours , melanoma . defect in NER . 40 percent do not make it.
chemical mutagens and the classed
- base analogs
- base modifiers
- intercalating agents
e.g chemical compounds , drugs , polycyclic aromatic hydrocarbon PAH ( barbecue )
a) direct
b)indirect ( form mutagentic metabolites through biotransformation )
basic stage only once they come in your body they become metabolised , biotransformation in the body they then become mutagens.
Base Analogs
substitue for DNA base during replication
e.g bromouracil which is an analog of thymine
AT goes to GC
so instead of thymine 5BRU is inserted which means , then the enol is produce but its not thymine anymore its C so gunaine inserts which is wrong . about three reps occur so from at - c g
Base modifiers
covalently modify the structures of a nucleotide
chemical mod of bases - incorrect base pairing , base substitution
intercalating agents
- flat planar structure
- insert between bases in DNA , distort DNA helix
two things can happen
ignore so deletetion occurs
or read so a new strand is created
- block transcription and replication
- frameshift mutations during replication
mutagens and cancer treatment
mutagens can be used as cancer treatment
- anti - neoplastic effect
highly toxic to proliferating cells
- chemotherapy
harm cancer plus normal cells
alkylating agents - cyclophosphamide and cisplatin
intercalating - danorubicin and doxorubicin - radiation therapy
ionizing radiation
character of mutations
gene mutations
- affect nucleotides
- do not affect morphology of CH
- point m
- deletion
- addition / insertion
in coding sequences
in non coding - stability of mrna , splicing
exons , promotors you can find them
point mutation
single base substitution
replacement of a single base nucleotide with an other nucleotide
transition
t to C
A to g
transversion
t to a or g
c to g or a
effects of gene mutation on a protein
silent - no change synonomous sub , no chance , degeneracy of genetic code
missense- nonsynonmous substitution , does make a difference . causes sickle cell anemia .
thus effects proteins function , sometimes it may still fucntion normally if its replaced with something of similar chemical properties . or if its in a region that does that really affect the proteins structure or function
nonsense mutation - codes for a premature stop codon ( TAA , TAG , TGA )
causes cystic fibrosis
Frameshift mutation - alteration in reading frame , involves deletions and insertions
causes tay sachs disease
tay sachs is a lysosomal storage disease , you have less HEXA ( hexa is a lysosomal hydrolytic enzyme ) lack of it leads to accumulation of Gm2 gangliosides which lead to cerebral degeneration plus blindness. popular with ashkenazi jew.
1000S Of mutations can be found in the cf gene , AF is the most popular one . for dieases normally more then one mutation in a gene
effect on function for classification of mutations
- gain of function
gain of a new and abnormal function
protooncogenes - oncogenes - loss of function
less or no function
enzymopathy
inactivation of tumour suppressors
-dominant negative
acts antagonistically to normal protein
-inactivation of tumour suppressors ( P53 )
cellular localization , classification of mutations
- mutations in nuclear DNA
- Mutations in mitochondrial DNA
- acquired
- inherited
defect in oxidative phophorylation
Mutagen vs carcinogen
mutagen
- agent that increases the frequency of mutations above the natural background level
carcinogen
- an agent directly involved in causing cancer
- carcinogens are mutagens
tetratogen
- an agent that can disturb the development of an embryo / fetus
- can cause birth defect in child / halt pregnancy outright
- radiation , maternal infections , chemicals and drugs
antimutagens
desmutagens
- antioxidants
-reduce the mutagenicity of mutagens
-neutralization of free radicals
- vitamin c ane
bioanitmutagens
-induce DNA repair
- vanillin , tannin , casein
what to do if you think someone might have a mutation
diseases caused by mutations
- inborn chromosomal abnormalities
- cancer
- monogenic disorders
- diseases with multifactorial inheritance
- mitochondrial diseases
