MT6315 GENETIC MUTATIONS Flashcards
(210 cards)
1
Q
GENETIC OR CHROMOSOMAL MUTATION: single gene is affected
A
GENETIC
2
Q
GENETIC OR CHROMOSOMAL MUTATION: low influence
A
GENETIC
3
Q
GENETIC OR CHROMOSOMAL MUTATION: sometimes lethal
A
CHROMOSOMAL
4
Q
GENETIC OR CHROMOSOMAL MUTATION: errors in DNA replication and mutagens
A
GENETIC
5
Q
GENETIC OR CHROMOSOMAL MUTATION: causes sickle cell anemia, hemophilia, CF
A
Genetic
6
Q
GENETIC OR CHROMOSOMAL MUTATION: error in crossing over
A
chromosomal
7
Q
GENETIC OR CHROMOSOMAL MUTATION: alteration in nucleotide sequence
A
GENETIC
8
Q
GENETIC OR CHROMOSOMAL MUTATION: several genes are affected
A
CHROMOSOMAL
9
Q
MUTATION OR POLYMORPHISM: <1% of the population
A
MUTATION
10
Q
MUTATION OR POLYMORPHISM: Not affected
A
POLY
11
Q
MUTATION OR POLYMORPHISM: Carrier; Diseased
A
MUTATION
12
Q
Genetic polymorphism has at least how many alternate DNA sequences?
A
2
13
Q
Genetic Polymorphism is generally not associated with disease but may cause the following?
A
result in phenotype
be a risk of disease
alter the function or
expression level of a protein
14
Q
any heritable change in the amount or structure of genetic material.
A
Mutation
15
Q
Classification of mutations can be based on?
A
Origin
Cell type
Expression
Effect on function
Molecular change and its effects on protein products
16
Q
POLYMORPHISM OR MUTATION: Physical event
A
MUTATION
17
Q
POLYMORPHISM OR MUTATION: presence of more than 1 allele at a particular locus in a particular population
A
POLYMORPHISM
18
Q
POLYMORPHISM OR MUTATION: permanent alteration of a nucleotide
A
MUTATION
19
Q
POLYMORPHISM OR MUTATION: Natural selection does not affect alleles
A
POLY
20
Q
POLYMORPHISM OR MUTATION: Natural selection selects
A
MUTATION
21
Q
POLYMORPHISM OR MUTATION: Human gender, ABO group
A
POLYMORPHISM
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Q
POLYMORPHISM OR MUTATION: Sickle cell anemia, CF, Klinefelter
A
MUTATION
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Q
Types of point mutation?
A
Silent
Missense
Nonsense
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Q
Types of frameshift mutation?
A
Addition
Deletion
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Types of Gene Mutation?
Point
Frameshift
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Genetic mutations based on origin?
Spontaneous
Induced
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TYPE OF MUTATION BASED ON ORIGIN: Occurs in absence of known mutagen
Spontaneous
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TYPE OF MUTATION BASED ON ORIGIN: Occurs in presence of known mutagen
Induced
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TYPE OF MUTATION BASED ON ORIGIN: Statistically random, unpredictable events
Spontaneous
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TYPE OF MUTATION BASED ON ORIGIN: happens in most mutations
Spontaneous
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T or F: Each gene has its rate of mutation
T
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The rate of mutation can (increase/decrease) with a mutagen or radiation
Increase
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an agent that changes genetic material
Mutagen
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Types of mutagens based on their effect?
Teratogens
Carcinogens
Clastogens
Non-specific
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WHAT TYPE OF MUTAGEN: Congenital malformations
TERATOGEN
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WHAT TYPE OF MUTAGEN: chromosomal abnormalities
CLASTO
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WHAT TYPE OF MUTAGEN: DNA damage
NON-SPECIFIC
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WHAT TYPE OF MUTAGEN: Tumor formation, cancer causing agents
CARCINO
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CLASSIFICATION OF MUTAGENS?
PHYSICAL
CHEMICAL
BIOLOGICAL
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EXOGENOUS OR ENDOGENOUS: UV-light
Exo
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EXOGENOUS OR ENDOGENOUS: Smoking
EXO
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EXOGENOUS OR ENDOGENOUS: Reactive oxygen species
Both
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EXOGENOUS OR ENDOGENOUS: Spontaneous or enzymatic DNA base modifications
ENDO
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EXOGENOUS OR ENDOGENOUS: DNA replication error
ENDO
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WHAT DAMAGING AGENT: Dipyrimidine photoproducts
UV
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WHAT DAMAGING AGENT: Bulky DNA adducts at guanines
Smoking (Benzopyrene)
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WHAT DAMAGING AGENT: Oxidation of guanine
Reactive O2 species
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WHAT DAMAGING AGENT: Deamination of 5-methylcytosine or cytosine
SPONTANEOUS OR ENZYMATIC DNA BASE MODIFICATIONS
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WHAT DAMAGING AGENT: mismatch
DNA REPLICATION ERROR
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Types of chemical mutagens?
Base analogs
Base altering agents
Intercalating agents
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Types of Base altering agents?
Deaminating agents
Hydroxylating agents
Alkylating agents
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Mutations based on cell type?
Somatic
Germ Line
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SOMATIC OR GERM LINE: Occurs in nonreproductive cells
SOMATIC
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SOMATIC OR GERM LINE: Can yield a genotypic mixture (mosaic) of normal and mutant tissue
SOMATIC
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SOMATIC OR GERM LINE: Most common cancers
SOMATIC
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SOMATIC OR GERM LINE: Autosomal
SOMATIC
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SOMATIC OR GERM LINE: non-inheritable
SOMATIC
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SOMATIC OR GERM LINE: Occurs in reproductive cells
GERM
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SOMATIC OR GERM LINE: common in sperm cells
GERM
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SOMATIC OR GERM LINE: Inherited
GERM
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What kind of mutations are common in sperm cells?
de novo
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T or F: In germ line mutations, not all inherit or have the mutation
F, all have the mutations
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In somatic mutations do all offspring have the mutation?
No, it is not inheritable
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Mutations based on expression?
Conditional
Unconditional
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TYPE OF MUTATION BASED ON EXPRESSION: Expressed only under restrictive conditions
CONDITIONAL
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TYPE OF MUTATION BASED ON EXPRESSION: Effect of mutation can be turned on or off by experimenter
CONDITIONAL
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Effect of mutation can be turned on or off by experimenter through the use of?
Transcription factors that turn off/on the gene
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TYPE OF MUTATION BASED ON EXPRESSION: Expressed under permissive conditions as well as restrictive conditions
UNCONDITIONAL
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"Normal conditions"
Permissive conditions
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What precipitates conditional expressions?
Restrictive conditions
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Types of mutations based on effect on function?
Loss of/amorphic (Knockout or null)
Hypermorphic (Leaky) -- loss of
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WHAT TYPE OF MUTATION BASED ON EFFECT ON FUNCTION: Eliminates normal function
LOSS OF
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WHAT TYPE OF MUTATION BASED ON EFFECT ON FUNCTION: Results in complete gene inactivation or in a completely nonfunctional gene product
LOSS OF
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Loss of function results in complete gene inactivation or in a completely nonfunctional gene product through?
Deletion of all or part of a gene or deletion of the part of the gene that helps in its expression
Amino acid replacement that inactivates the protein
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Example of amoprhic gene?
Bombay phenotype
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WHAT TYPE OF MUTATION BASED ON EFFECT ON FUNCTION: still has level of expression but it is severely reduced
LOSS OF
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WHAT TYPE OF MUTATION BASED ON EFFECT ON FUNCTION: Reduces normal function, but does not eliminate, the level of expression of a gene or the activity of the gene product
LOSS OF
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Individuals with loss of function may have enough enzyme activity to ____ to produce a quasi- normal phenotype
“leak through”
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LOSS OF OR GAIN OF: Hypermorphic
GAIN
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LOSS OF OR GAIN OF: Increases normal function; produces a greater than normal level of gene expression
GAIN
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LOSS OF OR GAIN OF: ectopic expression
GAIN OF
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WHAT MUTATION BASED ON EFFECT OF FUNCTION: Expressed at incorrect time or in inappropriate cell types
NEOMORPHIC
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WHAT MUTATION BASED ON EFFECT OF FUNCTION: Qualitatively alters the action of a gene
NEMORPHIC
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LOSS OF OR GAIN OF: Neomorphic
GAIN OF
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WHAT MUTATION BASED ON EFFECT OF FUNCTION: Mutant gene product interferes with normal gene product
ANTIMORPHIC
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LOSS OF OR GAIN OF: Antimorphic
LOSS OF
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WHAT MUTATION BASED ON EFFECT OF FUNCTION: creating abnormal proteins that replaces the normal one
ANTIMORPHIC
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Recessive mutations are usually (gain of/loss of) function.
LOSS OF
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Dominant mutations are usually (gain of/loss of) function.
BOTH
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MUTATIONS BASED ON MOLECULAR CHANGE?
Substitutions
* Deletions
* Insertions
* Duplications
Inversions
* Translocations
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In molecular genetics,
base pair substitutions are also termed?
point mutations
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In classical genetics, point mutations denote?
any mutation small enough to be unobservable under a microscope
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MUTATIONS Based on Molecular Change: Most common type of mutation
SUBSTITUTIONS
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MUTATIONS Based on Molecular Change: Replacement of a single nucleotide by another
SUBSTITUTIONS
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TYPES OF SUBSTITUTIONS?
TRANSITION
TRANSVERSION
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TYPE OF SUBSTITUTION: Replacement by the same type of nucleotide
TRANSITION
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TYPE OF SUBSTITUTION: pyrimidine for a pyrimidine (C for T or vice versa)
TRANSITION
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TYPE OF SUBSTITUTION: Most frequent due to CpG dinucleotides
TRANSITION
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TYPE OF SUBSTITUTION: purine for a purine (A for G or vice versa)
TRANSITION
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TYPE OF SUBSTITUTION: Substitution of a pyrimidine by a purine or vice versa
TRANSVERSION
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TYPE OF SUBSTITUTION: More silent
TRANSITION
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TRANSITION VS TRANSVERSION: Most common type of point mutation
TRANSITION
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TRANSITION VS TRANSVERSION: 2 possible
TRANSVERSION
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TRANSITION VS TRANSVERSION: One possible only
TRANSITION
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TRANSITION VS TRANSVERSION: more likely to cause amino acid sequence changes, more pronounced effect on the resulting protein
TRANSVERSION
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TRANSITION VS TRANSVERSION: Less likely to cause AA sequences, silent mutation
TRANSITION
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TRANSITION VS TRANSVERSION: Interchanges between bases within single ring structures
TRANSITION
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MUTATIONS Based on Molecular Change: Involves the loss of one or more nucleotides
DELETIONS
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TYPES OF DELETION PATTERNS?
MULTIPLES OF 3 NUCLEOTIDES (CODON)
NOT MULTIPLE OF 3
LARGE DELETION
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WHAT DEL PATTERN: Deletion of amino acids that may affect protein function or stability
Multiple of 3 nucleotides (codon)
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WHAT DEL PATTERN: Likely results to frameshift mutation
Not multiple of 3
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WHAT DEL PATTERN: May arise through unequal crossover between repeat sequences
Large deletion
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WHAT DEL PATTERN: Either: Partial gene deletion or Whole gene deletion
Large deletion
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Three-base deletion in the common cystic fibrosis (CF) allele results in synthesis of a protein that lacks amino acid ______
508 (phenylalanine).
115
MUTATION Based on Molecular Change: Involves the addition of one or more nucleotides into a gene
INSERTION
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TYPES OF INSERTION PATTERNS?
Multiple of 3 nucleotides (codon)
Not multiple of 3
Large insertion
Expansion of trinucleotide repeat (most contain C and/or G)
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WHAT TYPES OF INSERTION PATTERNS: Insertion of amino acids that may affect protein function or stability
Multiple of 3 nucleotides (codon)
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WHAT TYPES OF INSERTION PATTERNS: Likely results to frameshift mutation
Not multiple of 3
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WHAT TYPES OF INSERTION PATTERNS: Results from unequal crossover (e.g., hereditary sensory and motor neuropathy type 1a) or the insertion of transposable elements
Either: Partial gene duplication or Whole gene duplication
Large insertion
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WHAT TYPES OF INSERTION PATTERNS: Amplification of a sequence of three nucleotides, which prevents normal expression of the gene
Expansion of trinucleotide repeat (most contain C and/or G)
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WHAT TYPES OF INSERTION PATTERNS: Involves dynamic mutations wherein the repeat sequence becomes more unstable as it expands in size
Expansion of trinucleotide repeat (most contain C and/or G)
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Possible causes of Expansion of trinucleotide repeat (most contain C and/or G)?
Unequal sister chromatid exchange on nonreplicating DNA
Slipped-strand mispairing and polymerase slippage in replicating DNA
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Examples of disorders on the Expansion of trinucleotide repeat (most contain C and/or G)?
Fragile X syndrome (FMR1 gene) – CGG
Mutation
repeats
Huntington disease (HTT gene) – CAG repeats
Myotonic dystrophy (DMPK gene) – CTG repeats
Friedreich ataxia (FXN1 gene) – GAA repeats
124
MUTATIONS Based on Effect on Protein Products?
Synonymous
Nonsynonymous
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SYNO OR NONSYNO: Silent
SYNO
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Types of non synonymous mutations?
Missense mutations
Nonsense mutations Frameshift mutations
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SYNO OR NONSYNO: Mutation does not alter the polypeptide product of the gene
SYNO
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WHAT IS REFERRED TO AS "Base substitution occurs but does not change the amino acid sequence"
Silent mutations
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SYNO OR NONSYNO: Mutation leads to an alteration in the encoded polypeptide
NONSYNO
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SYNO OR NONSYNO: Likely to result in abnormal function, which is usually associated with disease,
or lethality
NONSYNO
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WHAT TYPE OF NONSYNO: Base-pair substitutions that produce a change in a single amino acid
MISSENSE
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WHAT TYPE OF NONSYNO: Change in amino acid may affect the protein structure
MISSENSE
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WHAT TYPE OF NONSYNO: Sickle cell anemia
MISSENSE
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Sickle cell anemia affects?
β-globin chain of hemoglobin at the position G
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What happens with the AA sequence changes in hemoglobin?
Hb crystallizes when O2 levels are low, causing RBCs to sickle and get stuck in small blood vessels
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WHAT TYPE OF NONSYNO: Base-pair substitutions that produce a stop codon in the mRNA
Nonsense mutations
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WHAT TYPE OF NONSYNO: Result in a premature termination of the polypeptide chain
Nonsense
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Base-pair substitutions that produce a stop codon in the mRNA results in?
premature termination of the polypeptide chain
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WHAT TYPE OF NONSYNO: Unlikely to retain normal biological activity, especially when there is a loss of an important functional domain(s) of the protein
Nonsense
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What is an example of nonsense mutation?
β0-thalassemia
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β0-thalassemia affects what in hemoglobin?
β-globin chain wherein codon for glutamine (CAG) creates a stop codon (UAG) as U is substituted for C
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WHAT TYPE OF NONSYNO: When a mutation involves the insertion or deletion of nucleotides that are not a multiple of three, it will disrupt the reading frame
Frameshift mutations
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WHAT TYPE OF NONSYNO: Resulting amino acid sequence bears no resemblance to the normal sequence and may have an adverse effect on its function
Frameshift mutations
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Example of frameshift mutation?
Single-base deletion at the ABO (glycosyltransferase) locus, leading to a frameshift mutation responsible for the O allele.
Tay-Sachs disease
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How is there frameshift in Tay-Sachs disease?
Four-base insertion in the hexosaminidase A gene
146
What is caused by greater than or equal to 40-121 CAG repeats?
HD
147
What level of penetrance of HD is 36-39 CAG repeats?
Reduced penetrance
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What level of penetrance of HD is 27-35 CAG repeats?
Mutable Normal Allele
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What level of penetrance of HD is less than or equal to 26 CAG repeats?
Normal alleles
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Types of splice site mutations?
Exon Skipping
Intron inclusion
Cryptic splice site use
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T OR F: All polymorphisms are equally detrimental for all populations
F, can be harmless to another and harmful to one
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When do somatic mutations usually occur?
Before mitosis
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When do germ line mutations usually occur?
DNA replication preceding meiosis
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Most mutations are spontaneous or induced?
Spontaneous
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"Surprise" mutation
Spontaneous
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Spontaneous mutation usually originates as an error in?
DNA replication
157
What triggers spontaneous mutations?
DNA bases existing in tautomers which can be inserted into the newly formed DNA causing errors
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T or F: Different genes have different spontaneous mutation rates
T
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Spontaneous mutation lies behind many instances of? Give an example disease
Somatic mutation
Proteus syndrome
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Spontaneous mutation also manifests as?
Gonadal mosaicism
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Why can mitochondrial genes mutate at a higher rate than the nucleus?
Mitochondria cannot repair their DNA
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Spontaneous mutation rate can be computed by?
de novo cases / 2X (X = individuals examined)
*2 is for non mutated homologous chromosome
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T or F: Spontaneous mutations are hard to assess
T
164
Where are mutations more likely to occur?
Hotspots
165
What dyes remove or add a single DNA base for induced mutations?
Acridine
166
Best known test for mutagenicity of substance?
Ames test - uses a strain of Salmonella that cannot grow when histidine is absent
167
T or F: Chemical mutagens are only artificial
F, can be seen in the environment
168
What mutation is seen only in certain conditions?
Conditional mutation
169
How to avoid conditional mutation?
Avoid exposure to certain triggers
170
T or F: Point mutations are visible under the microscope
F, unobservable
171
Until how many base pair inversions are NOT seen in karyotypes?
~500 pairs
172
Who are resistant to malaria?
Homozygous HbS and HbC individuals
173
Who is (+) for sickle cell anemia? HbS or HbC?
HbS
174
HbS and HbC result from?
Mutation in the 6th amino acid in the beta-globin polypeptide
175
If the beta-globing chain is dysfunctional, what happens?
RBC will crystallize and become sickle cell
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Detects numerical and gross structural aberrations
Karyotypes
177
Detects trisomies, monogamies, and microdeletions
FISH
178
Detects copy number variations of genetic material
CGH
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Depends on the melting point of DNA to detect its ability to stick
PCR testing
180
Detects missense mutations
PTT
181
A specific DNA sequence that varies in number of copies from person to person
Copy Number Variant
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What causes exon skipping?
A missense mutation that includes intron splicing sites in places where it should not be
183
Point mutation that alters the site where introns are normally removes from the mRNA
Splice-site mutation
184
Why is retaining an intron unusual?
Because it has stop codons
185
What are predictable because we are able to identify which codons can mutate to become a stop codon?
Nonsense mutations
186
What kind of mutagen: Halouracil and nitrogen mustard
Chemical
187
What kind of mutagen: Virus and bacteria
Biological
188
What kind of mutagen: X-rays and gamma rays
Physical
189
A point mutation can greatly affect a gene's product if it alters a site where introns are normally removed from the DNA. This is called a ____ mutation
Splice site
190
Thymine and cytosine dimerization are seen in ____ exposure in direct sunlight
UV-C
191
What is the most energetic ionizing radiations?
Gamma rays
192
A missense mutation that created an intron splicing site where there should not be one can cause ____, which removes a few contiguous AAs from the protein product
Exon skipping/ Frameshift
193
Major source of exposure to human-made radiation
X rays
194
Biological agent implicated in t8;14
Virus (EBV)
195
Mutagen used to label cells are like thymine but can pair up with either adenine or guanine which causes DNA replication
Bromouridine
196
The BS allele combined with a ____ HBB allele results in HbSB thalassemia disorder which is generally milder than sickle cell anemia
Leaky
197
Cytosines in ____ dinucleotides can be methylated to form 5-methylcytosines
CpG
198
Mutation of p53 gene is common in tobacco cancers, with a variation in the amount of G to T _____ in lung cancer from smokers and non-smokers
Transversions
199
T or F: Germ line mutation is the most common cause of cancers
F, somatic
200
T or F: Germ line mutation happens in egg and sperm cells
T
201
T or F: Genetic mutation have no effect on the individual at all
T
202
T or F: Silent mutations are not associated with any diseases
T
203
The methylation of __________ results in stable silencing of gene expression
CpG islands
204
The _____________ of CpG islands results in __________________ of gene expression
methylation
stable silencing
205
When do somatic mutations occur?
Before mitosis
206
When do germ line mutations occur?
During DNA replication before meiosis
207
How many CGG repeats in Fragile X syndrome is still viable for wild type phenotype?
30
208
How many CGG repeats in fragile X syndrome cause pre-mutation?
50-200
209
How many CGG repeats in fragile X syndrome cause the mutant allele?
>230, heavy methylation prevents normal transcription
210
What amino acid is affected in the missense mutation of sickle cell anemia?
Glutamic acid
