Mutation Flashcards
polymorphism
any genetic difference among individuals that is present in multiple individuals in a population
somatic mutation
occur in nonreproductive cells
passed via mitosis
germ-line mutations
occur in cells that give rise to gametes
meiosis transmission
heritable
raw material for evolution
sequential somatic mutations in cancer
series of mutations occur in the descendants of a single somatic cell. The first mutation occurs in a gene called APC, which normally inhibits abnormal cellular growth. The mutant APC cells begin to proliferate, but slowly.
Because mutations occur randomly and independently of existing mutations, there is a chance that one of the descendant APC cells will undergo a mutation in a gene called Ras. When a Ras mutation happens in a cell already carrying APC, the mutant cells divide even faster than before, but are still not malignant. But as they proliferate, there is a chance that one of the descendant cells will undergo a mutation in the gene p53.
This third mutation allow cells with further DNA damage to survive and divide extremely rapidly. And the cell lineage becomes malignant colon cancer
genetic risk factor
mutation that increases the risk of disease in an individual
multiple-mutation model for cancer development
Most human cancers require more than the overactivation of one oncogene or the inactivation of a single tumour suppressor
mutation rates
number of new mutations per genome per generation is not especially variable
mutation rate per genome per replication constant
higher for species with smaller genomes
greater rate of mutation in somatic cells
male mutation bias
mutation rate is higher in the male germline (sperm cells) compared to the female germline (egg cells). spermatogenesis throughout life time
most new mutations originate in males
older fathers-mutation rate increasing
indels
cant tell which sequence had an insertion/deletion
wobble base pairing
occurs with point mutations (substitutions)
transition
substitution of a purine for a purine or of a pyrimidine for a pyrimidine
small change in structural difference
pyrimidines
thymine and cytosine
purines
adenine and guanine
transversions
substitution of a pyrimidine for a purine or vice versa
transition:transversion
transitions more common
2:1
rate
copy number variation
form of genetic variation
number of copies of a particular segment of DNA varies between individual.
duplicated/deleted regions that include one or more genes
CNVs in coding regions cause tandem copies
tandem repeats
type of CNV
repeated sequences of DNA where the number of copies vary among individuals
the number of copies variation generates different alleles
DNA fingerprinting
how X rays cause mutation
cause breaks in the sugar-phosphate backbone
how UV light causes mutation
causes adjacent pyrimidines to cross -link forming thymine dimers which blocks replication
highly reactive chemicals and mutation
tend to be mutagenic as they can add bulky side groups to the bases
hinders proper base pairing
bleach/hydrogen peroxide and mutation
can cause loss of a base
gaps
tobacco smoke and mutation
adds bulky side groups to bases
improper base pairing
pyrimidine dimer
two thymine bases
block replication
SOS system bacteria
by pass replication block with a mutation-prone pathway
strand slippage, insertions
newly synthesised strand loops out resulting in the addition of a nucleotide on the new strand
strand slippage, deletions
template strand loops out resulting in the omission of one nucleotide on the new strand
repeated sequences have a —–rate of strand slippage
higher
unequal crossing over
if homologous chromosomes misalign during crossing over, one cross over product contains an insertion and the other a deletion
also caused by repeated sequences
repeat expansions
type of insertion
increase in number of copies of group of nucleotides beyond normal range
can be caused by repetitive sequences
fragile-X chromosome
constriction on long arm
CGG repeat expansion
strand slippage causes some individuals to have too many copes of it
more common in males
repeat expansion mechanism
DNA molecule normally has x copies of a repeat (eg CAG)
the 2 strands separate and replicate and in the course of replication, a hairpin forms on the newly synthesised strand (strand slippage)
part of template strand is replicated twice; increasing number of repeats on the newly synthesised strand
the newly synthesised strand acts as template next round so the resulting DNA molecule has >x copies of the (CAG) repeat
transposable elements/transposons
DNA sequences that can move from one position to another in the genome
can insert into a gene and disrupt its function
types of DNA damage repair
post-replication mismatch repair
base excision repair
nucleotide excision repair
DNA ligase
seals breaks in the sugar-phosphate backbone
uses energy from ATP to join the 3’ OH to 5’ phosphate
post-replication mismatch repair
a single mispaired base is repaired by removing and replacing a DNA segment.
base excision repair
the incorrect base and its sugar are excised from the strand then replaced
nucleotide excision repair
recognises multiple mismatched bases in a region
mismatch repair mechanism
mismatched bases recognised and a repair enzyme breaks the backbone downstream. another enzyme removes successive nucleotides, including the mismatched one. DNA polymerase adds the missing bases, DNA ligase joins backbones
base excision repair mechanism
enzyme recognises incorrect base and binds with the site, cleaving the base from the deoxyribose sugar. a different enzyme AP endonuclease recognises the site with missing base and binds with DNA to cleave the backbone in 2 places to free the sugar. leaves a gap. other enzymes bind with the site of the gap and insert a nucleotide with proper base pairing
nucleotide excision repair mechanism
one or more damaged bases signal repair process, enzymes cleave DNA backbone at these sites. region with damaged bases removed, gap filled by new DNA synthesis
forward mutation
wild type to mutant type
reverse mutation
mutant type to wild type
silent mutation
doesnt change amino acid sequence
codon to synonymous codon
missense mutation
amino acid to different amino acid
nonsense mutation
sense codon to nonsense (stop) codon
(introduction of premature stop codon)
causes truncation where nearly all truncated proteins are nonfunctional and unstable
deleterious mutations
decrease fitness
most extreme are lethal mutations
advantageous mutations
increase fitness
neutral mutations
no effect on fitness
epistasis
mutations effect in fitness also dependent on genetic background (other genes)
loss-of-function mutations
common
normally recessive
gain of function mutations
uncommon
normally dominant
conditional mutation
effect of mutation depends on something else, eg environmental condition
suppressor mutations
a mutation that hides or suppresses effects of another
can be inter or intragenic
