6: DNA mutation and damage

what are germ-line mutations

• in gametes - egg and sperm

• inherited by next generation

• present in al cells

what kind of mutations are sickle cell anemia, retinitis pigmentosa, aniridia, leber’s congenital amaurosis

germ-line mutation

what are somatic mutations

• in somatic cells - any cell except germline

• if cell proliferates, it forms cluster or identical cells containing same mutation

• can lead to tumors

• not inherited by next generation

what is a silent mutation

change in DNA sequence that does not change protein sequence or occurs in non-critical region of gene or outside of gene

what is a polymorphism

• normal variation in DNA sequence/genes within a population

• used for DNA ''fingerprinting, paternity analysis, and genetic mapping

what are hair color, eye color, blood types examples of

polymorphisms

single gene mutation

affects one gene

effect of mutation depend on type and location of change

chromosome mutation

• affects multiple genes

• typically causes defects

• often affects multiple organ systems (syndromic)

epigenetic changes

• chemical modifications of DNA that affect expression without altering sequence

• typically DNA methylation

• can permanently change gene expression

• can be inherited by daughter cells after cell division

what happens in transition

• purine replaces a purine

• pyrimidine replaces a pyrimidine

what happens in transversion

• purine replaces pyrimidine

• pyrimidine replaces purine

how many possible transition mutations are there

4

how many possible transversion mutations are there

8

what are the three types of point mutations

• silent - no effect on expression

• mis-sense - change amino acid

• non-sense -change to stop codon

what is conservative missense mutation

altered codon specifies a chemically similar amino acid

what is a nonconservative missense mutation

altered codon specifies a chemically dissimilar amino acid

what are indel mutations

• mutations that change the open reading frame

• can cause abnormal or nonfunctional proteins

• indel mutations that occur in multiples of 3 bases don’t change reading frame but adds/removes codons

what are trinucleotide repeats

• region of a repeated 3 base sequence

• length of repeats varies between individuals - sometimes used for DNA fingerprinting

what are these diseases associated with: fragile X, spinal and bulbar muscular atrophy, myotonic dystrophy, and huntington’s

excessive trinucleotide repeat expansion in or near some genes

what happens in depurination

• bond between base and deoxyribose broken by hydrolysis

• G or A base lost

• depurinated deoxyribose cannot specify base during replication

what happens in deamination

• deamination of cytosine makes uracil

• cell recognizes presence of uracil and tries to repair

• if not repaired, C to T transition occurs during replication

what is deamination

loss of amino group

what happens when 5-methyl-cytosine is deaminated to make thymine

change is usually not recognized and repaired which results in C to T transition during replication

what happens in oxidative stress

• reactive oxygen species and free radicals damage DNA

• oxidized bases block DNA replication or mispair during DNA replication

what happens when thymidine is oxidized

thymidine glycol blocks DNA replication

what happens when guanosine is oxidized

mispairs with A which created G to T transversion

other mechanisms of induced damage

• exposure to mutagens like chemicals, gamma rays, X rays for research purposes

• environmental exposure

  • UV light

  • pollution

  • pesticides

  • chemicals

  • radiation

what is a base analog

• chemicals with structures similar to nucleotides

• can be incorporated during DNA replication

what does ethylmethane sulfonate do to bases

mutagen that adds ethyl group to G or T bases

results in transitions (A to G and T to C)

what are DNA intercalating agents

• chemical structure that mimics paired bases

• fits into double helix between base pairs

• results in insertions and deletions during DNA replication

what does UV radiation do

• causes chemical attachment between adjacent pyrimidines

• disturbs double helix structure

• if not repaired, incorrect base is inserted during DNA replication

what do high doses of UV and ionizing irradiation do

will break DNA double helix and cause large scale DNA damage