10.3: mutation madness Flashcards
how can aneuploidies be detected?
- by comparing the dosage of DNA sequences from different chromosomes
Why are mutations both rare and common?
- rare because DNA replication occurs with high accuracy
- common because there is a LOT of DNA
what is the ultimate source of all variation?
genetic mutations!
What are somatic vs. germ line mutations?
- somatic: body cells, non heritable
- germ line: in gametic cells, heritable (may be transmitted to 50% of offspring)
what are the classifications of mutations based on the amino acid sequence?
- silent (synonymous), missense (non synonymous) and nonsense
how do indels impact amino acid sequences?
- indels can cause frameshift, resulting in missense or nonsense effects on proteins
- if in multiples of 3 however the RF is not affected
- indels outside RFS usually have no impact on phenotype
what are the mutation classifications based on impact on phenotype?
- loss of function: protein function completely or partially lost (recessive)
- gain of function : new gene product or gene product in wrong tissue (dominant)
- neutral : missense resulting in non significant change because it’s a chemically similar a.a or it occurs in a part of the protein not important for function
what are transitions and transversions? which is more common?
- transition: purine to purine, pyridine to pryimidine
- transversion: purine to pyrimidine, pyrimidine to purine
- transitions are more common despite there being half the options
what are the classes of forward and reverse mutations?
forward mutation: alters wild phenotype
reverse mutation: refers mutant back to wild type
- suppressor mutations: intragenic or intergenic mutations; where on mutations suppresses the other
How do mutations occur?
spontaneously or induced by chemical/physical agents
what are the 3 types of spontaneous mutations?
- tautomeric shifts, DNA strand slippage, misalignment of homologous chromosomes during crossing over
What are tautomeric shifts?
- proton ‘jumps’ around the molecule = proton shift
- base pairing: cytosine in its rare form can bind to adenine eg;
- causes incorrect base pairing during replication eg; base mismatch results in AC, one case its fixed (AT) and the other case its mutated (GC)
what is DNA strand slippage ?
- during DNA replication, an insertion or deletion occurs due to slipped strand mispairing
- eg;
- template strand slips out = omission of one base pair in the new strand
- new DNA strand slips out = insertion,
Describe misalignment of homologous chromosomes causing mutations?
- misalignment of homologous chromosomes during crossing over during meisois 1
- if homologous chromosomes misalign, one gains an insertion and the other gets a deletion
What are mutagens?
- agents that cause mutations
- eg; radiation and chemical mutagens
describe the types of radiation
- ionizing radiation: cosmic rays, X-rays, gamma rays
- UV radiation from sunlight
How does ionizing radiation impact the structure of molecules?
- rays hit the atom and cause an electron to be lost
- stable molecule becomes a free radicle or ion which can alter structure of bases and break phosphodiester bonds in DNA
Is UV radiation still damaging? Why? where does it come from and what is an example of a potential consequence?
- it’s longer wavelength, but still has potential to create radicals (not as commonly as the ionizing radiation though)
- common sources: the sun, mercury lamps, etc
- pyrimidine dimers: when the bases adjacent in DNA strand bind and cause a kink = can block DNA replication
how does DNA fix broken DNA?
- DNA repair enzymes use nucleotide excision repair
- proteins recognize incorrect matching, unwinds DNA, excises and replaces nucleotides
What is xeroderma pigmentosum?
- autosomal excessive disorder where the ability to repair mutations caused by UV is deficient
what are some other applications of UV radiation?
- Lamar flow hood, water, and sewage sterilization
- bacteria have no protection against UV
what are the 3 forms of chemical mutagens?
- base analogs, base modifying agents, intercalating agents
what are base analogs?
- chemicals that appear similar to bases but are not (‘trick’ the DNA)
- cause incorrect base pairing and introduces point mutations
what are base modifying agents?
- chemicals that modify groups of normal bases in DNA that results in incorrect base pairing and point mutations
what are intercalating agents?
- chemicals that distort normal base stacking in DNA: results in insertion or deletion
- planar molecules that insert between adjacent bases in DNA, distorting them by the size of a base
- during replication DNA pol selects any nucleoside to go opposite the intercalating agent = frameshift due to insertion
DOES NOT CHEMICALLY BIND
Amidst the thousands of man made chemicals, how can we know which are mutagenic? which test is best?
- the Ames test allows us to know which chemicals are mutagenic / carcinogenic!
how does the Ames test work?
- his- salmonella and his + salmonella
- increase reversions of his- to his+ (ie: more growth) indicates the chemical is a mutagen
what is the reliance of liver enzymes in the Ames test?
- liver enzymes seek to mimic human enzymes: can make the chemical more or less mutagenic
what good came from the Ames test?
- many chemicals identified as mutations and many removed / restricted in commercial use
- also shows that many naturally occurring compounds also have mutagenic properties
