2.6 Mutations Flashcards
What is ALS caused by?
can come from a couple mutations. Caused by fragile sites that are prone to breaks. Anticipation. Expands and when it gets too big, doesn’t fold correctly and forms placks.
What does the Tinman gene (NKX2.5) do?
Regulate heart development.
What are the modiators of early heart development?
Transcription factors.
Individual nucleotide changes in transcription factors can lead to what?
Specific outcomes
When do somatic mutations occur?
Something that happens post fertilization.
Can somatic mutations be passed on?
No
Where do somatic mutation arise in?
Tissues other than those that produce gametes
When do germ-line mutations occur?
Happens during meiosis and are in the germ line.
Where do germ-line mutations arise?
In tissues that produce gametes
Can germ-line mutations be passed on?
Yes
Are gene mutations always harmful?*
The majority are harmful but not always.
What is a De novo mutation?
Basically a new mutation.
What is a good example of a De novo mutation?
Cancer
Can De novo mutations be inherited?
No
What are the two categories to base substitutions?
Transition and transversion
What are the two categories for insertions and deletions?
Frameshift mutations, and in-frame insertions/deletions
What are expanding nucleotide repeats?
increase in the number of copies of a set of nucleotides
what does a base substitution alter?
a single codon
What does an insertion or a deletion alter?
many codons
What is a transition mutation?
Substitute a purine for a purine, same with a pyrimidine
What is a transversion mutation?
Substitute a purine for a pyrimidine and vice versa.
What is fragile X?
Region of number of repeats that is prone to mismatch repair and it can expand into generations (anticipation) once reaches threshold it’s a nonfunctional protein. Cognitive problems in bois
What is one disease that results from expanding nucleotide repeats?
ALS
What are 7 phenotypic effects of mutations?
Loss of function mutation. Neutral mutation. silent mutation. Missense mutation. Nonsense mutation. Forward mutation. Reverse mutation.
What is loss of function mutation?
Causes complete or partial absence of a normal protein function. Recessive.
What is a neutral mutation?
Alters AA seq but doesnt change the function of the protein
What is a silent mutation?
Changes the codon seq but not the AA
What is a missense mutation?
Base substit that results in a dif AA
What is a nonsense mutation?
Codon turns into a stop codon
What is a forward mutation?
Alters the wild-type phenotype
What is a reverse mutation?
Changes the mutant phenotype back into the wildtype.
Mutations affect coding sequence, but where can they also affect?
Promoter, non coding sequences, Splice sites
Which two mutations change the codon seq but not the AA?
Silent and Synonymous
What is the mutation for Charge syndrome?
C replaced by T. Resulting in a stop codon.. Nonsense mutation.
What are the two types of gene mutations?
Gain of function and suppressor mutation.
What are the two subcatagories of suppressor mutations?
Intragenic and intergenic
What is a gain of function mutation?
Produces a new trait.
What is a supressor mutation?
Hides or suppresses the effect of another mutation
What does intragenic mean?
Occurs in the same gene as that containing the mutation being suppressed
What does intergenic mean?
Occurs in gene other than the one bearing the original mutation
What is a lethal mutation?
Causes premature death
What is a frameshift mutation?
Insertion or deletion that alters the reading frame of a gene
What is an in-frame deletion or insertion?
Deletion or insertion of a multiple of 4 nucleotides that doesn’t alter the reading frame
What are 4 factors that affect mutation rates?
Freq with which a change takes place in DNA. Probability that when a change takes place, that change will be repaired. Environmental factors. Genetic background.
What is adaptive mutation good for?
Genetic variation critical for evolutionary change.
What 4 things are mutations potentially caused by?
Replication errors, chemical changes, chemically induced mutations, radiation
What are 4 examples of replication errors?
Tautomeric shifts, mispairing due to other structures, incorportation errors and replication errors, causes of deletion and insertions.
What are two causes of deletion and insertions?
strand slippage and unequal crossing over
What is non-watson and crick base pairing?
Mispairing due to altered protanation.
What does strand slippage result in?
Loss or gain of 1 nucleotide
What are InDels?
Unequal crossing over produces small inserts and deletions.
What is depurination?
Loss of a purine (A or G)
What is deamination?
Loss of an amino group (N)
What are 7 chemically induced mutations?
Mutagen, base analogues, Alkylating agents, Deamination, hydroxylamine, Oxidative reaction, intercalating agents.
What is a base analogue?
Chemical structure similar to normal bases.
What are two examples of base analogues?
5-bromouracil is analogue of T. Sometimes pairs with G. 2-Aminopurine pairs with T but may mispair with C
What are alkyating agents? What is an ex of them?
Donate alkyl group (methyl and ethyl groups). Mustard gas
What is deamination?
Nitrous acid
What does hydroxylamine do?
Add hydroxyl group
What are oxidative reactions? what is an ex?
Oxidative free radicals that convert G into something else that makes it mispair with A. Hydrogen peroxide
What do intercalating agents do?
Insert themselves between adjacent bases in DNA, distorting helix structure.
What are two forms of radiation?
Ionizing radiation and UV light
What does ionizing radiation do?
Dislodges e- in tissue causing free radicals which damage DNA
What does UV light do?
Induces pyrimidine dimers, that block replication
What is the SOS system in bacteria?
allows bac cells to bypass the replication block with a mutation prone pathway
What is the AMES test used for?*
To detect if something is mutagenic.
How does the AMES test work?
Bac strain cant synthesize histidine. If something is mutagenic, itll grow on the plate with the bac strain.
What are 4 pathways to repair changes in DNA?
Mismatch repair, direct repair, BER, NER
Many incorrectly inserted nucleotides that escape proof reading are corrected by what pathway?
mismatch repair
What is BER?
Repair mechanisms used to repair a nucleotide base.
What is NER?
Repair mechanisms used to repair a chunk of nucleotides.
What are two ways to repair ds breaks?
HR and nonhomologous end joining.
Which is more accurate? HR or NHEJ?
HR
What are translesion DNA polymerases used for?
Allow polys to skip over distortion but often leads to mutations
What does the direct repair system repair?
pyrimidine dimers
What does mismatch repair system repair?
Replication errors, mispaired bases and strand slippage.
What happens in bloom syndrome?
Mutations in the gene encoding DNA helicase RecQ, resulting in flaws in sister chromatid exchange.
What is Xeroderma Pigmentosum?
Abnormal skin pigmentation and acute sensitivity to sunlight. Have defective NER. Increased risk of skin cancer.
What is cockayne syndrome and trichothiodystrophy
Neuro problems, mutations in some of the same genes caused by XP. No increased risk of cancer however.
What is hereditary nonpolyposis colon cancer?
Responsible for 15% of colon cancers. Mutations in proteins that carry out mismatch repair process.
What sites are good for predicting if deleterious mutations are significant?
Mutation taster, polyphen-2, and Database of genomic variants
