Lecture 14 Flashcards
mutational hot spots
short repetitive sequences
palindromes
short repetitive sequences (mutational hot spot)
pairing of repeats may interfere with replication of repair enzymes
palindromes (mutational hot spot)
often associated with insertions or deletions
Does DNA symmetry increase or decrease the likelihood of mutation
increases
How are repeated genes prone to mutation?
by mispairing during meiosis
Induced mutation
Caused by mutages, many are also carcinogens and cause cancer
- ex: acridine dyes = add or remove base
- ex: radiation- breaks chromsome
Dimer mutation
An example of induced mutations because UV radiation creates thymine dimers, which is the mainc ause of melanoma skin cancers
Ames test
An in vitro test of the mutagenicity of a substance
One version uses Salmonella bacteria with mutation in gene for histidine
- Bacteria are exposed to test substance
- Growth on media without histidine is recorded
- Bacteria only grow if mutations have occurred
- Substance can be mixed with mammalian liver tissue prior to testing to mimic toxin processing in humans
Mutagen exposure
workplace industrial accidents - chernobyl medical treatments weapons natural sources (cosmic rays, sunlight, earth's crust)
Point mutations
A change of a single nucleotide
- transition - purine replaces purine or pyrimidine replaces pyrimidine
- transversion - purine replaces pyrimidine or pyrimidine replaces purine
consequences of point mutations
-missense mutation - replaces one amino acid with another
-nonsense mutation - changes a codon for an amino acid into a stop codon
a stop codon that is changed to a coding codon lengthens the protein
splice site mutations
alters a site where an intron is normally removed from mRNA
How can splice site mutations affect the phenotype?
- intron is translated or exon skipped (ex: CF mutation)
2. Exon is skipped (ex: familial dysautomia)
Deletions and Insertions
Nucleotide changes in multiples of 3:
- does not cause a frameshift mutation (disrupts the reading frame and alter amino acids after mutation)
- may alter the phenotype
Can different types of mutation cause the same single-gene disorder?
yes
pseudogenes
a DNA sequence similar to a gene but which is not translated
- may not even be transcribed into RNA
- may have evolved form original gene by duplication and acquired mutation
- crossing over between a psuedogene and function gene can disrupt gene expression
expanding repeats
insertion of triplet repeats leads to extra amino acids
- the longer proteins shut down the cells
- number of repeats correlates with earlier onset and more severe phenotype
Anticipation
the expansion of the triplet repeat with an increase in severity of phenotype with subsequent generations
An example of a triplet repeat disease
myotonic dystrophy
copy number variants (CNV)
- sequences that vary in number from person to person
- range in size from a few bases to millions
- account for about 25% of our genome
- CNVs may have no effect on the phenotype or they can disrupt a gene’s function and harm health
silent mutations
mutations that do not alter the encoded amino acid
synonymous codons
a mutation that alters the DNA but the protein sequence remains unchanged. for example CAA and CAG both code for glutamine. and therefore are synonymous codons.
Nonsynonymous codon
created by a missense mutation which alters the encoded amino acid to another amino acid
conditional mutation
produces a phenotype under particular condition or environments
ex: glucose 6-phosphate dehydrogenase enzyme, which responsds to oxidants, chemicals that strip electrons form other molecules
