Gene Mutations I and II Flashcards
Polymorphism meaning?
Natural variation in gene,DNA, Chromosome that has no adverse affects to the organism.
Benefit - population
Benefit evolution
natural variations in a gene, DNA sequence, or chromosome that have no adverse effects on the individual and…
occur with fairly high frequency in the general population.
Beneficial – Evolution
What is a Mutation? When occurs? Effect?
Change in genome, spontaneously, polymorphism
- Change in the genome - can occur spontaneously
- Produces genetic variation (polymorphism)
3.Gene mutation = change within a single gene
- One allele is mutated, to become another allele
4.Some mutations are point mutations, change in a single nt pair
Allele meaning?
Allele = one of a number of alternative forms of the same gene or same genetic locus
Mutation Nomenclature:
for
Bases, Deletion, Insertion, Amino Acids
5162 G –> A
5162= base position
G = orignal base
A = replacement base
Deletion: 197delAG
Insertion: 2552insT
R197G
R= Original Amino Acid
197 = AA position
G= Replacement AA
Wild type vs Mutant:
Wild-type: STANDARD GENOTYPE/PHENOTYPE
- Wild-type = found in nature or in the laboratory STOCK of the organism
Mutant: ALTERED genotype or phenotype (due TO MUTATION )
Origins of Mutations:
INDUCED VS SPONTANEOUS
Which one is the ultimate source of genetic variation? rate
- Induced = Treatment with Mutagen
- Spontaneous = Absence of mutagen
- Spontaneous mutations - ultimate source of genetic
variation
(DNA replication/repair).
- Rate is low - one cell in 10^5 - 10^8
What are Mutagens? how they effect?
Mutagens cause mutations - greater dose, more mutations
A mutagen is a CHEMICAL or PHYSICAL AGENT capable of INDUCING CHANGES in DNA called mutations
define mutagenesis?
the production of genetic mutations.
TYPE SOF MUTATIONS: POINT MUTATIONS
2? What are they?
Two main types:
- Base substitutions: one base pair is replaced by another
- Transition: replacement of a base by another base of the same chemical category (Purine ->Purine e.g. A ->G) or (Pyrimidine->Pyrimidine e.g. C ->T)
- Transversion: replacement of a base by another base of a different chemical category (Purine ->Pyrimidine e.g. A ->C) or (Pyrimidine->Purine e.g. C ->A) - Base insertions/deletions (indel): Insertion or deletion of nt pairs
Types of Base Substiutions:
Base substitutions: one base pair is replaced by another
- Transition: replacement of a base by another base of the same chemical category (Purine ->Purine e.g. A ->G) or (Pyrimidine->Pyrimidine e.g. C ->T)
- Transversion: replacement of a base by another base of a different chemical category (Purine ->Pyrimidine e.g. A ->C) or (Pyrimidine->Purine e.g. C ->A)
Types of Base Insertions/Deletions (indel):
Base insertions/deletions (indel):
Insertion or deletion of nt pairs
TYPES PF MUTATIONS = Point mutations at
***AT PROTEIN LEVEL (Protein coding part of a gene) =4
- Synonymous mutation – Codon change results in same AA (degeneracy of genetic code)
- Missense mutation (conservative/non) – Change in AA (to chemically similar
AA/chemically different AA - affects protein structure and function!!) - Nonsense mutation – Codon for one AA changed to STOP codon (premature
termination of translation – affects protein function e.g. inactive proteins) - Frameshift mutation – Indel (AA sequence downstream of mutation changed – loss of normal protein structure and function)
AMINO ACID CLASSIFICATIONS
NON POLAR -
POLAR -
ELECTRICALLY CHARGED- ACID VS BASIC
NON POLAR - Glycine, alanine, valine, leucine, isoleucine, methionine, tryptophan, phenylalanine, proline
POLAR - serine, threonine, cystine, tyrosine, asparagine, glutamine
ELECTRICALLY CHARGED-
ACID: apartic acid, Glutamic acid
BASIC: lysine, arginine, histidine
Transitions vs Transversions
TRANSITIONS
1. Purine to Purine
A - G
G - A
- PYRIMIDINE
T - C
C - T
TRANSVERSIONS
1. PURINE TO PYRAMIDINE
A-C
A-T
G-C
G-T
- PYRIMIDINE TO PURINE
C-A
C-G
T-A
T-G
Consequences of mutations within genes;
Types of Mutations at DNA level, Results at molecular level
NO MUTATION
TRANSITION OR TRANSVERSION
INSERTION OR DELETION
NO MUTATION: wild type
- Codons specify wild type protein
TRANSITION OR TRANSVERSION
- Synonymous mutation: Altered codon specifies the same A acid.
- Missense mutation (conservative):
Altered codon specifies a chemically similar amino acid - Missense Mutation (NONCONSERVATIVE):
Altered codon specifies a chemically dissimilar amino acid. - Nonsense mutation: Altered codon signals chain termination (STOP CODON)
INSERTION OR DELETION:
1. Frameshift mutation:
POINT MUTATION DO NOR ALWAYS HAVE PHENOTYPIC EFFECT:
Other than silent mutations, usually the least severe mutations in a protein coding gene result from missense mutations, but some missense mutations can be very deleterious…
Mutations can alter pre-mRNA Splicing
HOW? WHAT THE STEPS?
- Whole exon can be deleted as result of mutations in splice
signals,
e.g. Exon Skipping
2.Part of exon can be deleted as a result of mutations in normal splice signals cryptic splice site selection (sequences resembling normal splice signals)
Abnormal Splicing of b-globin
RNA in patients with b
thalassaemia (Mild to severe
anaemia)
Abnormal Splicing of b-globin
RNA in patients with b
thalassaemia (Mild to severe
anaemia)
PG 19
Different single-base mutations cause different splicing defects & disease:
WHAT ARE THEY? = 3
- Exon skipping
- Cryptic splice-site selection
- New splice site created
Wild type:
which way for Wild type and mutant?
Forward vs Reverse Mutation?
- Forward Mutation – alters WT
(Changes WT into a Mutant Phenotype)
Wildtype -> Mutant
2.Reverse Mutation – get WT
(Restores the WT phenotype)
Wildtype <- Mutant
Explain Reverse Mutations:
Exact reversion (true or genotypic) gives the wild type DNA sequence
Equivalent reversion gives a different DNA sequence, but the wild type AA sequence.
“reversion” is usually used to indicate reappearance of parental phenotype in a mutant organism caused,
Change in nt sequence to give back wild-type AA sequence, but not wild-type nt sequence…
Explain Suppressor mutation:
- “hides” the effect of another mutation.
- Distinct to exact reversion in which the mutated site changes back to original WT sequence.
- Occurs at a site distinct from the site of the original mutation.
- Double Mutant - Possesses original and suppressor mutation
but WT phenotype. - Two classes Intragenic and Intergenic
Intragenic vs Intergenic Supressor
both classes of Supressor mutation:
- Intragenic suppressor – mutation occurs in the gene
containing the original forward mutation
… Might change a second nucleotide in the same codon.
…Might also work by suppressing a frameshift mutation
- Intergenic suppressor – mutation occurs in a gene other than the one containing the original mutation that it supresses
action of an intergenic suppressor mutation,
steps
