Mutations Flashcards
1
Q
refer to the differences in DNA sequences among individuals, which lead to phenotypic differences in one or more characteristics.
These variations can be inherited from parents or occur spontaneously due to______ or ______
A
Genetic variants
mutations and recombination.
2
Q
– A permanent alteration in the DNA sequence of a gene.
This change may be small (affecting a single base) or large (involving entire chromosomes).
A
Mutation
3
Q
– The process by which genetic material is shuffled during meiosis, creating new combinations of alleles that contribute to genetic diversity.
A
Recombination
4
Q
is any alteration in the DNA sequence from the normal reference genome.
It can have a wide range of effects, from no impact at all to causing severe or even lethal consequences.
A
mutation
5
Q
are the smallest type of mutations, where a single nucleotide is altered.
Despite their small size, these mutations can have profound effects on protein function and phenotype
A
Point mutations
6
Q
occurs when one nucleotide is replaced by another.
This can lead to different consequences depending on how it affects protein translation.
A
base substitution
7
Q
is any alteration in the DNA sequence from the normal reference genome.
It can have a wide range of effects, from no impact at all to causing severe or even lethal consequences.
A
mutation
8
Q
Base Insertions and Deletions
A
INDELS
9
Q
INDELS
– Addition of one or more nucleotides into the DNA sequence.
– Removal of one or more nucleotides from the DNA sequence.
A
• Insertion
• Deletion
10
Q
These mutations can cause a frameshift, altering the entire reading frame of the gene, potentially leading to a nonfunctional protein.
A
INDELS
11
Q
Types of Base Substitutions
A
Transitions
Tansversions
12
Q
occurs when:
• A purine (A or G) is substituted by another purine.
• A pyrimidine (C or T) is substituted by another pyrimidine.
A
transition mutation
13
Q
Example:
• A → G (Purine to Purine)
• C → T (Pyrimidine to Pyrimidine)
A
Transition
14
Q
occurs when:
• A purine (A or G) is substituted by a pyrimidine (C or T), or vice versa.
A
transversion mutation
15
Q
Example:
• A → T (Purine to Pyrimidine)
• C → G (Pyrimidine to Purine)
A
transversion mutation
16
Q
The genetic code is______, meaning multiple codons can code for the same amino acid.
This redundancy provides some tolerance for mutations, reducing their harmful effects.
A
degenerate
17
Q
Degeneracy of the Genetic Code (_______)
• Many amino acids are coded by more than one codon.
• Exceptions: (2)
A
Wobble Hypothesis
• Tryptophan (Trp, W) → UGG
• Methionine (Met, M) → AUG
18
Q
A
19
Q
Stop Codons and Translation Termination
• Three codons serve as stop codons, signaling the end of protein synthesis:
A
• UAA
• UAG
• UGA
20
Q
The Wobble Hypothesis by…
A
(Francis Crick, 1996)
21
Q
explains how some tRNAs can recognize multiple codons that differ only in their third nucleotide position.
A
The Wobble Hypothesis
22
Q
The ribosome has two subunits:
– Responsible for mRNA decoding and proofreading at the first and second codon positions.
– Facilitates peptide bond formation.
A
• Small subunit
• Large subunit
23
Q
The____ of the codon is less strictly checked, allowing flexibility (or “wobbling”).
A
third position
24
Q
UCC, UCU, UCG → All code for_____, despite differences in the third base.
This flexibility allows the same amino acid to be produced even if a mutation occurs in the third nucleotide of a codon, reducing the impact of point mutations.
A
serine
25
arise due to mutations and recombination.
Genetic variants
26
Consequences of Point Mutations
1. Synonymous Mutations (Silent Mutations)
2. Missense Mutations (Nonsynonymous Mutations)
3. Nonsense Mutations
4. Indel Mutations (Insertions & Deletions)
5. Noncoding Region Mutations
27
occurs when a nucleotide substitution ***does not change the amino acid in the protein sequence.***
• This happens because the genetic code is degenerate, meaning multiple codons can code for the same amino acid.
A synonymous mutation
28
The third nucleotide in a codon is often flexible in pairing (Wobble Hypothesis), so mutations in this position frequently do not affect the final amino acid.
Synonymous Mutations (Silent Mutations)
29
occurs when a nucleotide substitution changes the codon to **£code for a different amino acid.***
• This can significantly alter protein structure and function.
A missense mutation
30
missense mutation
2 types
Conservative
Non conservative
31
• The new amino acid is chemically similar to the original.
• Protein function may not be significantly affected.
Conservative Missense Mutation
32
• Lysine → Histidine
(Both are basic amino acids).
Conservative Missense Mutation
33
Proline → Valine
(Both are non-polar amino acids).
Conservative Missense Mutation
34
• The ***new amino acid has different properties from the original.***
• Can lead to major structural and functional changes in the protein.
Non-Conservative Missense Mutation
35
Example:
• Glutamate → Valine
(Glutamate is acidic, Valine is non-polar).
Non-Conservative Missense Mutation
36
Some diseases result from missense mutations, such as…
Sickle Cell Anemia (Glu → Val in hemoglobin).
Non-Conservative Missense Mutation
37
occurs when a nucleotide substitution changes an amino acid codon into a stop codon (UAA, UAG, UGA).
nonsense mutation
38
This leads to premature termination of protein synthesis, creating a shortened, usually nonfunctional protein.
nonsense mutation
39
UAC (Tyrosine) → UAA (Stop codon)
Nonsense
40
• The protein loses its function, leading to severe consequences.
• The closer the mutation is to the 3’ end, the less damage it causes, as most of the protein may already be synthesized.
Nonsense
41
Nonsense mutation example
– Caused by nonsense mutations in the dystrophin gene, leading to loss of muscle function.
Duchenne Muscular Dystrophy
42
Insertion or deletion of nucleotides can lead to:
• ______mutations (if not a multiple of 3 nucleotides).
Frameshift
43
• Indel mutations affect all codons downstream, ***changing the entire amino acid sequence after the mutation.***
• Usually results in a ***nonfunctional protein.***
Frameshift Mutations
44
Example:
• Normal: ATG-TTC-GAA → (Met-Phe-Glu)
• mutation: ATG-GTT-CGA → (Met-Val-Arg)
Frameshift (insertion of G)
45
Most ***frameshift mutations cause complete loss of protein function.***
________is caused by a frameshift mutation in the HEXA gene.
• Tay-Sachs Disease
46
Strand Slippage & Frameshift Mutations
During DNA replication, the enzyme______ may make errors when copying repetitive sequences.
DNA polymerase
47
1. DNA polymerase “slips” on repetitive sequences.
2. The DNA strands loop and realign incorrectly.
3. This causes extra bases to be inserted or deleted.
Strand slippage
48
_____ occurs if slippage happens in the newly synthesized strand.
_____occurs if slippage happens in the template strand.
• Insertion
• Deletion
49
Example:
•______ is caused by expansion of CAG repeats (slippage in the newly synthesized strand).
Huntington’s Disease
50
Mutations in _______may or may not have an effect, depending on where they occur.
noncoding regions
51
1. No effect if it occurs in a non-functional region.
2. Disrupts regulatory elements (e.g., promoters, enhancers) → May increase or decrease gene expression.
3. Affects RNA splicing → Can lead to incorrect mRNA and protein formation.
Noncoding Region Mutations
52
● Functional consequences in this region depend on whether it disrupts or creates a binding site
● Many elicit little to no phenotypic change
● Can affect DNA processing if it happens on the
regulatory portion of the DNA
Noncoding Region Mutations
53
Naturally occurring mutations that
arise in all cells
SPONTANEOUS
54
Arise through the action of
mutagens that increase the rate of
mutations
INDUCED
55
• Naturally occurring mutations that happen in all cells due to DNA replication errors or chemical changes.
Spontaneous Mutations
56
• Mispairing of bases occurs (e.g., G-T instead of G-C).
• Can lead to transitions, transversions, or frameshifts.
Errors in DNA Replication
Spontaneous Mutations
57
• Bases exist in rare structural forms (tautomers), leading to incorrect base pairing.
Tautomeric Shifts
58
● Illegitimate nucleotide pairs form in DNA synthesis
(e.g. G-T instead of G-C)
● May lead to transitions and transversions, or frameshifts
SPOTANEOUS: ERRORS IN DNA REPLICATION
59
● Structual isomers of the bases and can co-exist in a solution, and would just interchange with one another at any point
● If they would become tautomers (imino/enol) → no longer become the normal bases
● Instead of paring adenine with thymine → Becomes
Adenine and Cytosine
TAUTOMERS
60
● Loss of a purine base
● Interruption of the N-glycosidic bond by hydrolysis
● The resulting apurinic sites cannot specify a base complementary to the original purine
DEPURINATION
61
● Loss of an amino group (NH2) from cytosine
Deamination
62
● Reactive oxygen species are produced by normal aerobic metabolism
● Causes oxidative damage to DNA and its precursors (e.g. GTP)
OXIDATIVE DAMAGE
63
Spontaneous Lesions
– Loss of a purine base (A/G), causing DNA damage.
– Removal of an amino group from cytosine, converting it to uracil.
– Reactive oxygen species (ROS) cause DNA mutations.
• Depurination
• Deamination
• Oxidative Damage
64
INDUCED MUTATIONS
→ T akes something that looks
like a base
→ changes the base → not
functional
→ destroy the base
● Base replacement
● Base alteration
● Base damage
65
● Base replacement
● Some chemical compounds are ***sufficiently similar to the normal bases of DNA*** and are called.…
● Does not behave like normal bases
● Incorrect base pairing
INDUCED: BASE ANALOG INCORPORATION
66
● Base alteration
● Alteration of a base such that it will form a specific mispair
E.g. ethylmethanesulfonate and nitrosoguanidine
INDUCED: SPECIFIC MISPAIRING
67
● Planar molecules that ***mimic base pairs***
● Can slip in between stacked nitrogen bases
● E.g. acridine orange (fluorescent stain)
INDUCED: INTERCALATING AGENTS
68
● Damage to one or more bases
● No specific base pairing is possible, resulting in a
replication block
● E.g. UV light, ionizing radiation, aflatoxins
INDUCED: BASE DAMAGE
69
Example: 2-Aminopurine (mimics adenine but pairs with cytosine)
Base Replacement (Base Analogs)
70
Example: Alkylating agents (e.g., EMS) modify guanine, making it pair with thymine.
Base Alteration (Specific Mispairing)
71
Example: Acridine orange (fluorescent stain that can mutate DNA).
Intercalating Agents
72
Examples:
• UV light → Forms thymine dimers, distorting DNA.
• Ionizing radiation → Breaks DNA strands.
• Aflatoxins (from fungi) → Cause bulky DNA adducts.
Base Damage (Replication Block)
73
involve alterations in either the number or structure of chromosomes.
These changes can significantly affect an organism’s development, survival, and overall function
Chromosomal changes
74
: A genetic variant that controls a specific trait.
Different... can exist for the same gene, affecting characteristics such as eye color, blood type, or disease susceptibility.
Allele
75
: Organisms that have the normal number of complete chromosome sets for their species.
Euploid
76
: Individuals with missing or extra chromosomes that do not form a complete set.
Aneuploid
77
: Individuals with one or more extra sets of chromosomes.
Polyploid
78
Chromosome number variations arise due to errors in cell division. These errors can lead to (2)
aberrant euploidy (whole chromosome set changes)
aneuploidy (changes in individual chromosome number).
79
• Occurs when the ***entire set of chromosomes is increased or decreased*** from the normal diploid (2n) number.
• These changes affect an organism’s viability and reproductive ability.
ABERRANT EUPLOIDY
80
Types of Aberrant Euploidy:
Monoploidy
Polyploidy
81
• _____have only one complete set of chromosomes instead of two.
• In diploid species, it is typically lethal, as a single chromosome set cannot provide backup copies of essential genes.
Monoploids
82
• In some insects, such as male bees, ants, and wasps, monoploidy is normal because males develop from unfertilized eggs and have only one chromosome set.
Monoploid
83
(3n, 4n, etc.)
• Occurs when an organism has extra complete sets of chromosomes.
• More common in plants than in animals.
Polyploidy
84
Example:
• Strawberries are octoploid (8n), meaning they have eight sets of chromosomes, making them larger and more robust.
• Wheat has different ploidy levels, with some varieties being hexaploid (6n).
Polyploidy
85
occurs when an individual has an abnormal number of chromosomes—either missing or extra chromosomes.
Aneuploidy
86
Unlike________, which affects entire sets,_____ alters only a part of the chromosome set.
aberrant euploidy
aneuploidy
87
● Chromosome number differs from the wild type by a
part of the chromosome set
● Can have a number greater or smaller than the
wildtype
Aneuploidy
88
________occurs when chromosomes fail to separate properly during cell division (either meiosis I, meiosis II, or mitosis).
• This results in gametes (sperm or egg cells) with abnormal chromosome numbers, which, when fertilized, can lead to aneuploid offspring.
Nondisjunction
89
● Cause of most aneuploidy in the course of meiosis or mitosis
NONDISJUNCTION
90
● Missing one copy of a chromosome
● Monosomic autosomes = die in utero
● e.g. Turner syndrome (XO)
MONOSOMY (2n-1)
91
● Has one extra copy of a chromosome
Abnormality/death
● e.g. Klinefelter syndrome (XXY)
TRISOMY (2n+1)
92
Types of Aneuploidy Caused by Nondisjunction:
Monosomy
Trisomy
93
→ Missing one chromosome
• Results in severe developmental issues and is often lethal in autosomal chromosomes.
Monosomy (2n - 1)
94
Turner syndrome (XO) → Affected individuals have only one X chromosome instead of two (45 chromosomes instead of 46).
Monosomy (2n - 1)
95
→ One extra chromosome
• Causes developmental abnormalities and can be lethal in some cases.
Trisomy (2n + 1)
96
Trisomy (2n + 1)
Down Syndrome (Trisomy____)
Edwards Syndrome (Trisomy____)
Patau Syndrome (Trisomy____)
Klinefelter Syndrome (____)
21
18
13
XXY
97
refers to the ratio of gene products (proteins and RNA) that are necessary for maintaining normal cellular and physiological function.
This balance is critical because any disruption in the ratio of gene expression can lead to abnormalities and diseases.
Gene balance
98
• ______have a gain or loss of specific chromosomes, disrupting the gene balance significantly.
Aneuploids
99
• ______, on the other hand, have additional entire sets of chromosomes, which keeps the gene ratio relatively balanced.
Polyploids
100
• ______has extra copies of genes on the affected chromosome, increasing the production of certain proteins.
• ______lacks one chromosome, reducing the amount of proteins made by the missing genes.
• This imbalance leads to severe developmental defects because the body cannot regulate processes properly
A trisomic individual (2n + 1)
A monosomic individual (2n - 1)
101
Why Are Monosomics More Severely Affected Than Trisomics?
• Monosomics (2n - 1) have only one copy of the genes on the missing chromosome, which can be lethal because essential genes may be lost entirely.
• Trisomics (2n + 1) still have extra copies of genes, which disrupt the gene balance but are often more tolerable than a complete loss of genes.
102
• Affected females lack one X chromosome.
• Symptoms include short stature, heart defects, infertility, and developmental issues.
Turner Syndrome (Monosomy X - 45, XO)
103
• Individuals have an extra chromosome 21.
• Causes intellectual disabilities, characteristic facial features, and heart problems.
Down Syndrome (Trisomy 21 - 47, XX or XY, +21)
104
Mechanism:…
• In females (XX), one X chromosome is randomly inactivated in each cell to balance gene expression between males and females.
• The inactivated X chromosome becomes a Barr body and is not transcribed.
X-Chromosome Inactivation (Lyonization)
105
→ Change the gene dosage (increasing or decreasing the amount of genetic material).
→ Change the gene order only (without altering gene dosage).
Unbalanced rearrangements
Balanced rearrangements
106
107
• A segment of the chromosome is reversed (flipped 180°) within the same chromosome.
Inversions
108
Types of Inversions:
______
• Does not involve the centromere.
• The inverted segment is away from the centromere.
______
• Includes the centromere within the inverted region.
• Can lead to problems during meiosis, causing unbalanced gametes.
1. Paracentric Inversion
2. Pericentric Inversion
109
• Involves the exchange of genetic material between ***two non-homologous chromosomes.***
• This means that pieces of two different chromosomes swap places without a net gain or loss of genetic material.
Reciprocal Translocation
110
Clinical Example: Chronic Myeloid Leukemia (CML)
• Caused by a ______ between chromosomes 9 and 22, forming the Philadelphia chromosome.
• This translocation creates a fusion gene (BCR-ABL1), leading to uncontrolled cell division and leukemia.
Reciprocal Translocation
111
Cancer-promoting mutations:
○ Increase in proliferation ability
○ Decrease susceptibility to apoptosis
○ Increase general mutation rate of the cell
○ Increased longevity
112
Proto-Oncogenes → Oncogenes (Gain-of-Function Mutation)
• _______are normal genes that regulate cell growth and division.
• When mutated, they become____, which overstimulate cell division and lead to cance
Proto-oncogenes
oncogenes
113
(Loss-of-Function Mutation)
Tumor-Suppressor Genes
114
• normally prevent uncontrolled cell growth.
• If mutated or lost, these genes fail to stop abnormal cell division, leading to cancer.
Tumor-suppressor genes
115
“Guardian of the Genome” – The…
p53 Tumor-Suppressor Gene
116
is a tumor-suppressor
that detects DNA damage and stops the cell cycle to allow repairs.
p53
117
If damage is too severe,_____ triggers apoptosis (programmed cell death).
• 50% of all human cancers involve mutations in the this gene, making it one of the most critical tumor-suppressor genes.
p53
118
→ A translocation between chromosomes 9 and 22 creates the BCR-ABL fusion gene, leading to uncontrolled cell division in leukemia
Philadelphia Chromosome (CML)
