UNIT 6: GENETIC MUTATIONS Flashcards
alteration in the chromosome structure or chromosome number
Chromosomal mutation
<1% of population
Mutation
> 1% of population
Polymorphism
A wobble has a maximum of ___ permissible changes.
1/3
At least two alternate DNA sequences; generally not assoc. with diseases
Genetic polymorphism
any heritable change in the amount or structure of genetic material
Genetic mutation
Classification of mutations can be based on
Origin
Cell type
Expression
Effect on function
Molecular change and its e ffects on protein products
Choice of testing for genetic mutations
Probing using molecular tests like FISH and CGH
Test for chromosomal mutation
Karyotyping
For polymorphism, single base pair change in the nucleotide sequence is called a
Single nucleotide polymorphism
For mutation, single base pair change in the nucleotide sequence is called a
Point mutation
the DNA polymerase’s ability to correct changes in the DNA
Fidelity
rapidly dividing cells are more prone to have a mutation due to
Adaptability
Based on Origin
Spontaneous / Induced
Occurs in the absence of known mutagen
Statistically random, unpredictable events
Spontaneous
Occurs in presence of known mutagen
Usage of offending agent
Induced
Mutagens based on effect
Teratogens
Carcinogens
Clastogens
Non-specific
an agent that changes genetic material
Mutagen
Teratogens result in
Congenital malformation
Rapid, uncontrollable proliferation of cells
Cancer
There is a limitation on how we can control mutation and its e ffect on environmental or population genetics.
Drift-barrier hypothesis
Teratogens affect the overall structure because they target __________ stem cells
pluripotent
Carcinogens result in
Tumor formation
Cancer
Clastogens result in
Chromosomal abnormalities
Nonspecific mutagens result in
DNA Damage
3 Classifications of Mutagens
Physical
Chemical
Biological
Physical mutagens
I Hate Nothing
- Ionizing radiation
- Heat
- Non-ionizing radiation
are like bullets; cause double stranded breaks
ex. X-rays, Cosmic rays, Gamma rays
Ionizing radiations
high-energy enough to cause thymine dimerization
ex. UV rays
Non-ionizing radiations
Part of atomic decay
ex. Alpha particle, Beta particle, Fast neutron, Thermal neutron
Heat
Chemical mutagens
ADI agents
- Alkylating agents
- Deaminating agents
- Intercalating agents
Stain that can cause cancer
would get inside the double stranded DNA
Ethidium Bromide (EtBr)
Biological Mutagens
BB agents
- Biological agents
- Biological infectious agents
Examples of Biological agents
Virus
Bacteria
Transposons
Natural elements of DNA that jump
Transposons
In cases of sunburn, what is removed from the DNA by the corrective mechanism of the body?
Thymine dimer
Most energetic type of UV light
UV C
Hydrocarbon involved in smoking
Polycyclic Aromatic Hydrocarbons (PAH)
Hydrocarbons involved in smoking
Polycyclic Aromatic Hydrocarbons (PAH)
In smoking, bulky DNA adducts at _______
guanines
Hydrogen peroxide is reversed by
Vitamins
Hydrogen peroxide is reversed by
Vitamins
mostly harmful to the body but useful in neutrophils
Oxygen free radicals
Transformation of structure
ex. C to 5mC
Tautomerization
corrects dipyrimidine photoproducts in some organisms
not present in humans
Photolyases
mimics the bases
similar but not exactly the same
Base analogs
chemotherapy medication used to treat various types of cancer, including leukemia, lymphoma, neuroblastoma, and Wilms tumor
Vincristine
chemotherapy medication, typically used with other medications, to treat a number of types of cancer including Hodgkin’s lymphoma, non-small-cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer
Vinblastine
Based on Cell type
Somatic and Germ line
Occurs in nonreproductive cells
Can yield a genotypic mixture (mosaic) of normal and mutant tissue
Most common cancers
Somatic
Occurs in reproductive cells
Inherited
Can be de novo from the parent passed to the offspring
Germ line
Sperms are associated with germ line mutations because
they are more prone to errors in mutation
paternal : genetic mutation
maternal: ___________
aneuploidy
Examples of Germ line mutation
Sickle cell anemia, cystic fibrosis, and color blindness
Based on Expression
Conditional
Unconditional
Expressed only under restrictive conditions (ex. high temperature)
Effect of mutation can be turned on or off by experimenter
Conditional
Expressed under permissive conditions as well as restrictive condition
Expressed all the time with no preconditions
Unconditional
Based on Effect on Function
Loss of function (amorphic and hypomorphic)
Gain of function (hypermorphic, neomorph, antimorphic)
Based on Effect on Function
Loss (amorphic and hypomorphic) and Gain (hypermorphic, neomorphic, and antimorphic)
other name for amorphic mutation
knockout or null mutation
Eliminates normal function
Results in complete gene inactivation or in a completely nonfunctional gene product
Amorphic
other name for Hypomorphic mutation
leaky mutation
Reduces normal function, but does not eliminate, the level of expression of a gene or the activity of the gene product
Hypomorphic
Individuals with hypomorphic mutations may have enough enzyme activity to “leak through” to produce a _____________ phenotype
quasi-normal
Increases normal function
Produces a greater-than-normal level of gene expression (mutation changes the regulation of the gene so that the gene product is overproduced)
Hypermorphic
other name for neomorph
ectopic expression
other name for neomorph
ectopic expression
Expressed at incorrect time or in inappropriate cell types (new function)
Qualitatively alters the action of a gene
Neomorph
Mutant gene product interferes with normal gene product
Antimorphic
Based on Molecular Change
Substitutions
Deletions
Insertions
Duplications
Inversions
Translocations
In molecular genetics, base-pair substitutions are also termed _______ ____________
point mutations
In classical genetics, point mutations denote any mutation that are
small enough to be unobservable under a microscope
temporarily stop or decrease the expression of one or more targeted genes
Gene knockdown
Most common type of mutation
Substitution
Replacement by the same type of nucleotide
ex. C for T; A for G
Transition Substitution
Substitution of a pyrimidine by a purine or vice versa
ex. A for T; C for G
Transversion Substitution
Defense mechanism in substitution
Degeneracy
the ability of elements that are structurally different to perform the same function or yield the same output
Degeneracy
the regions in the DNA sequence, which comprises cytosine followed by guanine from 5′ to 3′ direction
CpG sites
most common type of point mutation
Transition substitution
Involves the loss of one or more nucleotides
Deletion
Deletion of amino acids that may affect protein function or stability
Multiple of 3 nucleotides (codon)
Deletion pattern that likely results in frameshift mutation
Not multiple of 3
Deletion of amino acids that may affect protein function or stability
Multiple of 3 (codon)
Deletion that may arise through unequal crossover between repeat sequences
Either: Partial gene deletion or Whole gene deletion
Large deletion
Three-base deletion in the common cystic fibrosis (CF) allele results in synthesis of a protein that lacks:
amino acid 508 (phenylalanine)
Involves the addition of one or more nucleotides into a gene
Insertion
Insertion of amino acids that may affect protein function or stability
Multiple of 3 nucleotides (codon)
Insertion pattern that likely results to frameshift mutation
Not multiple of 3
Results from unequal crossover (e.g., hereditary sensory and motor neuropathy
type 1a) or the insertion of transposable elements
Large insertion
examples of Expansion of trinucleotide repeat
Huntington disease
Triple X syndrome
Myotonic dystrophy
Friedreich ataxia
Amplification of a sequence of three nucleotides, which prevents normal expression of the gene
Involves dynamic mutations wherein the repeat sequence becomes more unstable as it expands in size
Expansion of trinucleotide repeat
Expansion of trinucleotide repeat mostly contains bases __ and/or __
C ; G
Based on Effect on Protein Products
Synonymous (silent) and Nonsynonymous (missense, nonsense, and frameshift)
Mutation does not alter the polypeptide product of the gene
Synonymous
Mutation leads to an alteration in the encoded polypeptide
Likely to result in abnormal function, which is usually associated with disease, or lethality
Nonsynonymous
Base-pair substitutions that produce a change in a single amino acid
Missense
substitution involving different groups of amino acids
nonconservative missense mutation
substitution involving same groups of amino acids
conservative missense mutation
Sickle cell anemia affects the _________ ______ of hemoglobin
β-globin chain
Amino acids involved in sickle cell anemia
Glutamic acid (normal) to Valine (mutant) at the 6th position out of 147 AA
Base-pair substitutions that produce a stop codon in the mRNA
Result in a premature termination of the polypeptide chain
Unlikely to retain normal biological activity, especially when there is a loss of an important functional domain(s) of the protein
Nonsense
Nonsense mutation wherein the codon for glutamine (CAG) creates a stop codon (UAG) as U, substituted for C
β0-thalassemia
When a mutation involves the insertion or deletion of nucleotides that are not a multiple of three
Resulting amino acid sequence bears no resemblance to the normal sequence and may have an adverse effect on its function
Frameshift
Other term for Frameshift mutation
indel
Frameshift mutation that involves a four-base (TATC) insertion in the hexosaminidase A gene
Tay-Sachs disease
mutation that happens in areas where exons must be cut and stick together
Splice Site Mutation
Types of Splice Site Mutation
Exon skipping, Intron inclusion, Cryptic
Consequence of Frameshift mutation
From mutation to end of the sequence is incorrect
