01:447:380 Lecture Notes - Lecture 10: Nonsense Mutation, Mutation, Stop Codon
27 Apr 2018
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Lecture 9 Review and overview: DNA mutation and repair
I. Wild-type sequence: all changes in the DNA base sequence are referred to as a mutation for the
purposes of this unit
a. Mutations depending on the demand the environment takes on the organism
i. Helpful detrimental neutral
ii. Necessary for evolution
iii. Mechanisms for new characteristics
II. Forward, reverse and suppressor mutations
a. Reverse mutation, aka reversion, replaces the original (forward) mutation and restores
the wild-type genotype and phenotype
b. Suppressor mutation is at another site, but it compensates for the mutation and restore
the wildtype phenotype
i. Suppressor mutations can hide or suppress the effects of other mutations
ii. The individual is a double mutant, but has a normal phenotype
iii. Some suppressor mutations are intragenic—ithi the sae gee’s odig
sequence
1. Ex. C G nonsense mutation creates a UAG STOP codon where there
was a UAC tyrosine codon
c. Germline Versus Somatic Mutations
i. Germline mutations—Present in either (or both) the sperm or the egg that
made the individual, therefore present in every cell the individual has
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ii. Somatic mutations—Arise after fertilization, during cell
replication/division/differentiation/migration, therefore only present in a subset
of the idiidual’s ells
1. Somatic mutation that arises in the S phase : gets passed down to ¼ of
the descendants of the original cell (slide 8)
2. Can be passed down to offspring
a. If the mutation exists in the cells that make sperm
(spermatogonia) or eggs (oogonia), the mutation can be
packaged into a gamete
b. Fro the offsprig’s perspetie, this is a germline mutation—it
was present in one of the gametes that made the child, and it
will exist in every cell the child has
c. Fro the paret’s perspetie, it is a somatic mutation—it
occurred after fertilization and only existed in a subset of the
paret’s ells
iii. Some mutation are conditional
1. Conditional mutation—Some mutations only cause consequences
under certain conditions
a. Ex. Many people who have a glucose-6-phosphate
dehydrogenase deficiency (an X-linked recessive disease) will
eperiee flare-ups ai spto = heolti aeia if
they eat fava beans
iv. Some Mutations Involve Large Pieces Of One Or More Chromosomes
1. Structural Abnormalities
a. Deletions and duplications range in size from single nucleotides
to pieces of the chromosome that are large enough to include
many genes in them
b. Inversions and translocations that rearrange large pieces of
chromosomes
i. DDIT: Dude do IT
2. Numerical Abnormalities
a. Entire chromosomes can be added or deleted
b. More on this when we discuss cytogenetics
v. The Smallest Mutations Are :Single-Nucleotide Point Mutations
1. Point mutation = substitution, deletion or addition of a single
nucleotide
a. NO change:
i. benign polymorphisms: no change in activity of protein
ii. silent mutations: do’t hage the orgais’s
PHENOTYPE
iii. Synonymous mutations: does’t hage the aio
acid content of the protein
1. Synonymous And Intronic Mutations May
Change The Pattern Of RNA Splicing (slide 19)
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2.
iv. Neutral mutation: changes the amino acid content of
the protein but has no functional consequences
1. BSSN NO CHANGE
b. Variable effects on phenotype
i. that alter protein activity may increase or decrease it,
by a small or large amount
ii. If the amino acid substitution, deletion or addition
hages the protei’s 3D shape or ailit to oe as it
orks, it ill disrupt the protei’s futio
iii. The degree to hih it alters the protei’s ailit to
bend and move determines how severely it affects
protein activity
iv. Slides 14-18
2. Transition = purine-purine substitution or pyrimidine-pyrimidine
substitution
3. Transversion = purine-pyrimidine substitution or vice versa
4. Missense mutation—single-nucleotide substitution causes one amino
acid to replace another
5. Nonsense mutation—single-nucleotide substitution creates a STOP
codon at the site of the mutation, and truncates the protein
a. PTTMN: Pink ticklish tiny mammary nipples
b. Nuc [purines and pyrimidine (Matches)(switches)(Nuc sub–
amino amio)] (nuc sub - stop codon @ mutation site
truncates protein)
6. Synonymous And Intronic Mutations May Change The Pattern Of RNA
Splicing
a. Most human introns begin with GT and end with AG
i. If a mutation creates a new splice site (ex. a C T
mutation changes a GC that lies in an exon to a GT),
the spliceosome will splice the pre-mRNA abnormally
ii. This will either add intronic nucleotides to the mRNA
or delete exonic nucleotides from the mRNA
iii. Either way, this changes the instructions the ribosome
gets, and it will incorporate the wrong amino acids
into the polypeptide—this almost always abolishes the
activity of the protein
7. Insertions and deletions may shift the ribosomes reading frame
a. Slide 20-22 read this shit
8. Mutation in the regulatory sequences affects the rate of protein
production
a. Coding sequence: mutations can change the activity of each
molecule of the protein
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Document Summary
Phenotype: synonymous mutations: does(cid:374)"t (cid:272)ha(cid:374)ge the a(cid:373)i(cid:374)o acid content of the protein, synonymous and intronic mutations may. Function: expansion most common but can contract, expand or contract it depends on the parent of origin, more likely to contract during. Repeat in the x chromosome (xq28: chromosomes from cells that are grown in culture will show fragile sites, where they look stretched out as if the chromosome was about to break. There are common fragile sites all over the ge(cid:374)o(cid:373)e, i(cid:374) e(cid:448)er(cid:455)o(cid:374)e"s (cid:272)hro(cid:373)oso(cid:373)es these are not associated with disease: there are also rare fragile sites that are associated with diseases ex. Cgg repeat and the fmr1 gene promoter get methylated, which silences the gene: the frax trinucleotide repeat can also contract during meiosis, the repeat is more likely to contract during. 45% of the human genome has come from transposons: slides 32 48.
