Gene Mutations Flashcards
(235 cards)
1
Q
What are some of the physical characteristics exhibited by Vincent?
A
Arched eyebrows, extra-long lashes, bluish eye whites, offset ears, additional teeth, webbed neck, small lower jaw, elastic skin, brittle hair
2
Q
What developmental and medical conditions does Vincent have?
A
Developmental delay
Autistic behaviors
Learning disability
3
Q
How did Marc recognize a syndrome in his son, Vincent?
A
Marc, having an interest in genetics, recognized a syndrome in Vincent due to his unusual combination of characteristics.
4
Q
What was the result of the exome sequencing done on Vincent?
A
Vincent was found to have a de novo mutation in the gene RPS23, which encodes one of the proteins that make up ribosomes.
5
Q
What organisms did researchers use to study Vincent’s mutation?
A
Zebrafish and mice were among the model organisms used to study Vincent’s mutation.
6
Q
How did Marc eventually find other individuals with similar conditions to Vincent?
A
Marc entered Vincent’s information into GeneMatcher, an online tool part of the Matchmaker Exchange, which connects parents, researchers, and healthcare professionals to identify mutations behind rare diseases.
7
Q
What was the outcome of using GeneMatcher for Vincent’s case?
A
Within three months of entering Vincent’s mutation, Marc learned of another child with the same phenotype and genotype, leading to a better understanding of the condition and potential avenues for treatment.
8
Q
What broader impacts did Vincent’s case have on scientific research?
A
Vincent’s case led to potential advancements in understanding autism and ribosomes, as well as the development of therapies for rare diseases with similar genetic mutations.
9
Q
What is a mutation?
A
A mutation is a change in a DNA sequence that is rare in a population and typically affects the phenotype.
10
Q
What are the different types of mutations?
A
Mutations range from substitution of a single DNA base to deletion or duplication of entire chromosomes.
11
Q
What effects can mutations have?
A
Mutations may impair a function, have no effect, or even be beneficial, altering protein production, secretion, location, or interaction.
12
Q
How do mutation, polymorphism, and variant differ?
A
Mutation refers to rare genetic changes, polymorphism indicates common variations, and variant encompasses both based on frequency and impact.
13
Q
What is the difference between germline and somatic mutations?
A
Germline mutations occur in cells before meiosis, affecting all cells in an individual and can be passed on to offspring. Somatic mutations occur in non-reproductive cells after fertilization, affecting only a portion of the individual’s body.
14
Q
Which parts of the genome can mutations affect?
A
Mutations can affect sequences encoding proteins or controlling transcription, introns, repeats, and sites critical to intron removal and exon splicing.
15
Q
Are all DNA sequences equally likely to mutate?
A
No, not all DNA sequences are equally likely to mutate, with factors such as gene function, environmental influences, and genetic background playing a role.
16
Q
Can mutations ever be beneficial?
A
Yes, some mutations can confer advantages, such as resistance to certain diseases, providing insights into evolutionary processes.
17
Q
How often do somatic mutations occur?
A
Somatic mutations occur roughly every 300 mitotic cell divisions and are more common in cells that divide frequently.
18
Q
How is somatic mosaicism clinically relevant?
A
Somatic mosaicism is implicated in certain genetic diseases, with varying degrees of severity depending on the affected cells.
19
Q
What challenges arise in genetic testing?
A
Identifying and interpreting variants of uncertain significance can complicate clinical decisions based on genetic testing results.
20
Q
Can you provide an example of a beneficial mutation mentioned in the text?
A
The mutation in the CCR5 gene, which confers resistance to HIV infection, is an example of a beneficial mutation.
21
Q
Why are some DNA sequences more prone to mutation than others?
A
Factors such as gene function, environmental influences, and genetic background can influence mutation frequency, leading to variability in mutation rates across different regions of the genome.
22
Q
How does understanding mutations contribute to medical practice and genetics?
A
Knowledge of mutations is essential for diagnosing genetic disorders, developing targeted therapies, and understanding evolutionary processes.
23
Q
What are some broader implications of somatic mosaicism?
A
Somatic mosaicism plays a role in cancer development, personalized medicine, and our understanding of genetic diversity within individuals.
24
Q
What are some ethical dilemmas related to genetic testing mentioned in the text?
A
Ethical challenges include identifying and reporting variants of uncertain significance, protecting patient privacy, and ensuring informed consent in genetic testing procedures.
25
How do mutations contribute to evolutionary processes?
Mutations introduce genetic variation within populations, which serves as raw material for natural selection and evolutionary change over time.
26
What role does genetic counseling play in the context of mutations and genetic testing?
Genetic counselors provide guidance and support to individuals and families regarding the implications of genetic test results, including the interpretation of variants of uncertain significance and the risk of inherited conditions.
27
How do cells mitigate the effects of mutations?
Cells have DNA repair mechanisms that help correct DNA damage and errors, reducing the likelihood of mutations and maintaining genomic stability.
28
What are the long-term implications of genetic variation within populations?
Genetic variation allows populations to adapt to changing environments and can contribute to the survival and evolutionary success of species.
29
What was the first genetic illness understood at the molecular level?
Sickle cell disease
30
What substitution mutation occurs in sickle cell disease?
The substitution of valine for the normal glutamic acid as the sixth amino acid in the beta globin polypeptide chain.
31
What is the DNA level change in sickle cell disease?
A CTC is changed to a CAC, corresponding to RNA codons GAG and GUG.
32
How does the substitution of valine affect hemoglobin molecules in sickle cell disease?
It changes the surfaces of hemoglobin molecules, causing them to attach at more points in low-oxygen conditions.
33
What do aggregated hemoglobin molecules form in sickle cell disease?
Ropelike cables that make red blood cells sticky and able to deform, bending them into rigid, fragile sickle shapes.
34
What are some symptoms of sickle cell disease?
Pain in blocked body parts (particularly hands, feet, and intestines), bone ache, and fatigue due to anemia.
35
What is thalassemia, and why was it named so?
Thalassemia is a condition resulting from mutations in the beta globin gene. It was named from the Greek for "sea" due to its high prevalence in the Mediterranean area.
36
What are the two forms of thalassemia, and how do they differ?
Thalassemia major results from a homozygous mutation in the beta globin gene, while thalassemia minor affects individuals who are heterozygous for the mutation.
37
What is the molecular basis of beta thalassemia?
It results from too few beta globin chains, leading to insufficient assembly of hemoglobin molecules to deliver oxygen effectively to tissues.
38
How does severe beta thalassemia progress, and what complications arise?
Excess alpha globin chains prevent the formation of hemoglobin molecules, leading to organ damage from liberated iron. Periodic blood transfusions can control anemia but hasten iron buildup and organ damage.
39
What is collagen, and what is its significance in the body?
Collagen is a major component of connective tissue, providing structural support to various body parts such as bone, skin, ligaments, and tendons.
40
How many collagen genes encode different types of collagen molecules?
More than 35 collagen genes encode more than 20 types of collagen molecules.
41
What happens to procollagen to form mature collagen?
Procollagen is trimmed, and enzymes snip off the ragged ends of the procollagen polypeptides to form mature collagen.
42
What are some consequences of mutations affecting collagen?
Mutations affecting collagen can lead to various medical conditions, including osteogenesis imperfecta (brittle bone disease) and disruptions in connective tissue integrity.
43
What is Marfan syndrome, and how does it relate to collagen?
Marfan syndrome is a genetic disorder affecting connective tissue, characterized by mutations in the genes that encode collagen. It can lead to aortic aneurysm and other connective tissue abnormalities.
44
How can mutations in collagen genes affect the triple helix structure of collagen?
Mutations in collagen genes can remove procollagen chains, kink the triple helix, or disrupt aggregation outside the cell, leading to structural abnormalities in collagen.
45
Why are mutations affecting collagen particularly devastating?
Mutations affecting collagen are particularly devastating because collagen has an extremely precise conformation that is easily disrupted, even by slight alterations, due to its widespread presence and crucial role in maintaining tissue integrity.
46
What is the significance of the amino acid glycine in collagen?
Glycine plays a crucial role in collagen structure as it is the only amino acid small enough to fit within the very tight helical structure of collagen.
47
How can Marfan syndrome be detected before symptoms arise?
Marfan syndrome can be detected before symptoms arise through genetic testing to identify mutations associated with the condition. Additionally, frequent ultrasound exams can detect aortic weakening early, potentially preventing life-threatening complications.
48
What genes encode the polypeptide chains of collagen?
The α1 collagen gene encodes the two blue polypeptide chains, while the α2 procollagen gene encodes the third (red) chain.
49
How is the procollagen triple helix modified before becoming functional?
The procollagen triple helix is shortened before it becomes functional, forming the fibrils and networks that comprise much of the human body.
50
What is the consequence of collagen mutations on the skin in Ehlers-Danlos syndrome type I?
Collagen mutations in Ehlers-Danlos syndrome type I cause highly extensible joints and stretchy skin due to the inability of collagen molecules to assemble properly.
51
What disease is associated with mutations in the cystic fibrosis transmembrane regulator (CFTR) protein?
Cystic fibrosis
52
What is the consequence of missing amino acid or other variants in the CFTR protein?
Altered conformation of chloride channels in certain epithelial cell plasma membranes, leading to the drying out of secretions.
53
What are the signs and symptoms associated with cystic fibrosis?
Frequent lung infections and pancreatic insufficiency.
54
Which protein is affected by mutations in Duchenne muscular dystrophy?
Dystrophin
55
What are the signs and symptoms of Duchenne muscular dystrophy?
Gradual loss of muscle function.
56
What is the consequence of deficient LDL receptors in familial hypercholesterolemia?
Accumulation of cholesterol in the blood.
56
What is the consequence of deletion in the dystrophin protein?
Elimination of dystrophin, which normally binds the inner face of muscle cells to the plasma membrane, leading to muscle weakening.
57
Which protein is affected in familial hypercholesterolemia?
LDL receptor
58
What are the signs and symptoms associated with familial hypercholesterolemia?
High blood cholesterol levels and early heart disease.
59
What protein is affected in hemophilia B?
Factor IX
60
What is the consequence of absent or deficient Factor IX in hemophilia B?
Slow or absent blood clotting.
61
What are the signs and symptoms of hemophilia B?
Hard-to-control bleeding.
62
Which protein is affected in Huntington's disease?
Huntingtin
63
What is the consequence of extra bases adding amino acids to the huntingtin protein in Huntington's disease?
Impairment of certain transcription factors and proteasomes, leading to uncontrollable movements and personality changes.
64
What are the signs and symptoms of Huntington's disease?
Uncontrollable movements and personality changes.
65
What proteins are affected in Marfan syndrome?
Fibrillin or transforming growth factor β receptor
66
What are the consequences of deficient proteins in Marfan syndrome?
Cataracts in the lenses and aneurysms in the wall of the aor
67
What are the signs and symptoms associated with Marfan syndrome?
Long limbs, weakened aorta, spindly fingers, sunken chest, lens dislocation.
68
Which protein is affected in Neurofibromatosis type 1?
Neurofibromin
69
What is the consequence of defects in neurofibromin protein?
Abnormal growths due to the suppression of activity of a gene that causes cell division.
70
What are the signs and symptoms of Neurofibromatosis type 1?
Pigmented skin patches and benign tumors of nervous tissue beneath the skin.
71
What concept is changing the description of single-gene diseases?
Analysis of human genomes is changing the way we describe single-gene diseases.
72
What were geneticists inconsistent with in the past regarding disease names?
Geneticists were inconsistent when assigning disease names to mutations.
73
What term describes different clinical phenotypes caused by mutations in the same gene?
Different clinical phenotypes caused by mutations in the same gene are termed allelic diseases.
74
Can you provide examples of allelic diseases?
Mutations in the CFTR gene cause cystic fibrosis, while different mutations in the beta globin gene cause sickle cell disease and beta thalassemia.
75
What gene illustrates how different mutations cause different diseases in different tissues?
The lamin A gene illustrates how different mutations cause different diseases in different tissues.
76
How do mutations in some genes correspond to many diseases?
Mutations in some genes correspond to many diseases, such as the gene lamin A, where different mutations cause different diseases in different tissues.
77
How do allelic diseases arise from mutations?
Allelic diseases may result from mutations in different parts of the gene, including localized mutations or catastrophic mutations, or mutations altering the protein's interactions with other proteins.
78
What are some examples of diseases caused by mutations in the lamin A gene?
Diseases caused by mutations in the lamin A gene include Hutchinson-Gilford progeria syndrome, muscular dystrophies, and heart disease.
79
How are researchers reclassifying cystic fibrosis?
Some researchers are reclassifying cystic fibrosis as two allelic diseases based on whether the lungs are affected.
80
What variability exists in disease manifestations caused by mutations in the CFTR gene?
Mutations in the CFTR gene can result in cystic fibrosis with varying manifestations, ranging from respiratory and digestive issues to male infertility or frequent bronchitis.
81
How do mutations in the beta globin gene contribute to allelic diseases?
Mutations in the beta globin gene can lead to sickle cell disease and beta thalassemia.
82
What roles do mutations play in the occurrence of allelic diseases?
Allelic diseases can arise from mutations in different parts of the gene, including localized mutations or catastrophic mutations, or mutations altering the protein's interactions with other proteins.
83
What diseases illustrate the concept of allelic diseases?
Cystic fibrosis and sickle cell disease are examples of diseases that illustrate the concept of allelic diseases.
84
What is the gene associated with Menkes disease and peripheral neuropathy?
ATP7A
85
What diseases are associated with the DMD gene?
Duchenne and Becker muscular dystrophy
86
Which gene encodes fibrillin-1 and is associated with Marfan syndrome?
FBN1
87
What diseases are associated with the FGFR3 gene?
Two types of dwarfism
88
Which gene is associated with Gaucher disease and Parkinson's disease?
GBA
89
What diseases are associated with the PSEN1 gene?
Acne inversa and Alzheimer's disease
90
Which oncogene is associated with multiple endocrine neoplasia and Hirschsprung disease?
RET
91
What diseases are associated with the TRPV4 gene?
Peripheral neuropathy and spinal muscular atrophy
92
What is a spontaneous mutation?
A spontaneous mutation is one that occurs naturally, often as a result of errors in DNA replication.
93
What can trigger a spontaneous mutation?
Spontaneous mutations can be triggered by errors in DNA replication, such as the insertion of unstable DNA bases.
94
What is the spontaneous mutation rate?
The spontaneous mutation rate varies among genes, with some having higher rates than others. It is estimated based on observations of new dominant conditions, such as achondroplasia.
95
How can the spontaneous mutation rate for autosomal genes be estimated?
The spontaneous mutation rate for autosomal genes can be estimated using the formula: number of de novo cases divided by 2 times the number of individuals examined.
96
What are mutational hot spots?
Mutational hot spots are regions within genes where mutations are more likely to occur, often due to repetitive sequences.
97
How do palindromes affect the spontaneous mutation rate?
Palindromes can increase the spontaneous mutation rate by disturbing DNA replication, leading to small additions or deletions of DNA bases.
98
What is induced mutation?
Induced mutation is when mutations are deliberately caused by exposure to mutagens such as chemicals or radiation.
99
What are alkylating agents and how do they induce mutations?
Alkylating agents are chemicals that remove a DNA base, leading to mismatches when the base is replaced during DNA replication.
100
What is the Ames test used for?
The Ames test is used to assess the mutagenicity of substances by observing their effects on rapidly reproducing bacteria, particularly their ability to enable growth on deficient medium.
101
What is site-directed mutagenesis?
Site-directed mutagenesis is a technique used to intentionally introduce changes to a gene in a desired way, allowing for precise manipulation of DNA sequences.Site-directed mutagenesis is a technique used to intentionally introduce changes to a gene in a desired way, allowing for precise manipulation of DNA sequences.
102
How do acridines induce mutations?
Acridines add or remove a single DNA base, which can disrupt the DNA sequence and alter the amino acid sequence of the encoded protein
103
What are some examples of mutagens used to induce mutations?
Mutagens used to induce mutations include alkylating agents, acridines, and various chemicals or forms of radiation that alter DNA sequences.
104
How do X-rays induce mutations?
X-rays and other forms of radiation can delete a few bases or break chromosomes, leading to mutations.
105
What are the limitations of using mutagens to induce mutations?
Mutagens cannot cause specific mutations, and their effects can be unpredictable. Additionally, many mutagens are also carcinogens, increasing the risk of cancer.
106
What is the impact of mutagens on human health?
Mutagens can contribute to various health issues, including cancer. Common products containing mutagens include hair dye, smoked meats, flame retardants used in children's sleepwear, and certain food additives.
107
What are some examples of techniques for gene editing?
Gene editing techniques such as those described in sections 19.4 and 20.4 are mentioned, which can rapidly introduce changes to DNA sequences.
108
How do researchers infer a gene's normal function?
Researchers infer a gene's normal function by observing the effects of mutations that alter it, often using model organisms such as mice and fruit flies.
109
How do researchers test the mutagenicity of substances?
Researchers use various methods to test the mutagenicity of substances, including the Ames test, which assesses the ability of substances to induce mutations in rapidly reproducing bacteria.
110
What are some examples of mutagenic substances identified?
Examples of mutagenic substances include chemicals used in hair dye, certain food additives, and components of cigarette smoke.
111
What are some examples of accidental exposures to mutagens?
Accidental exposures to mutagens can occur through workplace contact before the danger is known, industrial accidents, medical treatments like chemotherapy and radiation, exposure to radiation-emitting weapons, and natural disasters damaging radiation-emitting equipment.
112
Can you provide an example of an accidental mutagen exposure incident?
One notable incident occurred on April 25, 1986, when Reactor 4 at the Chernobyl Nuclear Power Station in Ukraine exploded, releasing a plume of radioactive isotopes into the air, leading to acute radiation exposure and subsequent deaths.
113
How did the Chernobyl disaster affect nearby residents?
Evidence suggests a mutagenic effect, such as a 10-fold increase in thyroid cancer rates among children living near the Chernobyl plant in Belarus. Thyroid glands absorbed radioactive iodine released during the disaster.
114
How do researchers track mutation rates following the Chernobyl explosion?
Researchers compare the lengths of short DNA repeats, called minisatellite sequences, in children born after the accident and their parents who lived in the exposed area. Differences in minisatellite sizes indicate mutations in parental gametes.
115
What are some sources of natural exposure to mutagens?
Natural sources of mutagen exposure include cosmic rays, sunlight, and radioactive substances in the Earth’s crust, such as radium, which produces radon. Medical X rays and occupational radiation hazards add risk.
116
What are the major types of ionizing radiation?
The major types of ionizing radiation are alpha, beta, and gamma rays. Alpha radiation is least energetic and absorbed by the skin; beta radiation penetrates farther into the body, and gamma rays are highly penetrating.
117
How does ionizing radiation affect DNA?
Ionizing radiation breaks the DNA sugar-phosphate backbone, potentially leading to mutations. Alpha and beta radiations are generally less harmful, while gamma rays, being highly penetrating, can damage tissues deeply.
118
What is the significance of X-rays in mutagenic exposure?
X-rays, a major source of human-made radiation, have less energy compared to gamma rays but can still cause damage, particularly in medical settings where they are commonly used for diagnostics.
119
What are the effects of radiation damage to DNA?
Radiation damage to DNA can lead to mutations, especially in oncogenes or tumor suppressor genes, potentially causing cancer. It can also cause genome-wide destabilization, leading to mutations even after cell division.
120
What complicates the evaluation of chemical mutagens' risk?
Evaluating the risk of chemical mutagens is difficult due to variations in individual susceptibilities and exposure to multiple chemicals. The risk from chemical exposure may be less than the natural variability in susceptibility within a population, making tracking mutational events challenging.
121
What are mutations classified by?
Mutations are classified by whether they remove, alter, or add a function, or by how they structurally alter DNA.
122
How can a single-gene disease result from different types of mutations?
The same single-gene disease can result from different types of mutations.
123
Point mutations
Changes in a single DNA base.
124
What is a transition in terms of point mutations?
A transition is a point mutation that replaces a purine with a purine or a pyrimidine with a pyrimidine.
125
Explain transversion in point mutations.
A transversion replaces a purine with a pyrimidine, or vice versa.
126
How is addition or deletion of a single DNA base considered in point mutations?
Addition or deletion of a single DNA base is also considered a point mutation.
127
What are the consequences of a point mutation?
A point mutation can have several consequences, including no effect on phenotype (silent mutation).
128
What is a missense mutation?
A missense mutation changes a codon specifying a particular amino acid into one that codes for a different amino acid.
129
How does a nonsense mutation differ from a missense mutation?
A nonsense mutation changes a codon specifying an amino acid into a "stop" codon.
130
Describe the consequence of a premature stop codon.
A premature stop codon shortens the protein product, potentially influencing the phenotype.
131
What is nonsense-mediated decay, and how does it relate to mutations?
Nonsense-mediated decay is a response that destroys mRNAs with premature stop codons, which is protective against harmful shortened proteins.
132
What is the opposite of a nonsense mutation?
The opposite of a nonsense mutation is when a normal stop codon mutates into a codon specifying an amino acid, resulting in a longer protein.
133
How can point mutations affect transcription?
Point mutations can control transcription, affecting the quantity rather than the quality of a protein.
134
What is a splice-site mutation?
A splice-site mutation greatly affects a gene's product by altering a site where introns are normally removed from the mRNA.
135
How can a splice-site mutation affect the phenotype?
A splice-site mutation can affect the phenotype by translating introns into amino acids or skipping exons, shortening the protein.
136
What is the consequence of retaining an intron due to a mutation?
Retaining an intron adds bases to the protein-coding part of mRNA, potentially affecting protein structure and function.
137
How can a missense mutation create an intron splicing site?
A missense mutation can create an intron splicing site, leading to exon skipping and removal of contiguous amino acids from the protein product.
137
Describe the impact of exon skipping mutation on protein production.
An exon skipping mutation causes deletion at the mRNA level but is a single-base mutation at the DNA level, resulting in removal of entire exons during translation.
138
Explain the phenomenon observed in some diseases caused by exon skipping mutations.
Some cells may ignore the mutation and produce a normal protein from the affected gene, resulting in a less severe phenotype depending on which cells make the full encoded protein.
139
How does exon skipping inspire drug development for certain diseases?
Exon skipping observed in diseases inspired the development of drugs to restore retention of skipped exons in mRNAs, potentially mitigating disease symptoms.
140
What is a frameshift mutation?
A frameshift mutation results from the addition or deletion of bases that are not a multiple of three, disrupting the gene's reading frame.
141
How does a frameshift mutation affect protein production?
A frameshift mutation leads to a shortened protein due to alteration of the reading frame.
142
Explain the impact of a deletion mutation.
A deletion mutation removes DNA, potentially altering the phenotype.
143
Describe the consequence of an insertion mutation.
An insertion mutation adds DNA, offsetting the reading frame and potentially affecting protein production.
144
What is a tandem duplication mutation?
A tandem duplication mutation occurs when part of a gene's sequence is repeated adjacent or close to the original sequence.
145
Provide an example of a disease caused by a tandem duplication mutation.
Charcot-Marie-Tooth disease, which causes numb hands and feet, can result from a tandem duplication mutation.
146
What is a pseudogene?
A pseudogene is a DNA sequence similar to a protein-encoding gene but not translated into protein, potentially descended from a duplicated gene sequence that mutated to become non-functional.
147
How do pseudogenes form?
Pseudogenes can form when DNA strands misalign during meiosis, leading to duplication of a gene sequence. Mutations in one of the duplicated genes render it non-functional, resulting in a pseudogene.
148
How can pseudogenes interfere with gene expression?
Pseudogenes can interfere with gene expression by causing mutations or crossovers with functional genes, leading to diseases like Gaucher disease.
149
What are transposons?
Transposons, also known as "jumping genes," are DNA sequences capable of changing their positions within a genome, potentially disrupting gene function or causing mutations.
150
How do transposons affect gene function?
Transposons can disrupt genes they jump into, alter gene expression, or affect reading frames, leading to changes in protein synthesis and potentially causing diseases like hemophilia.
151
What is an expanding repeat mutation?
An expanding repeat mutation is a type of mutation where a gene grows due to the addition of repeated DNA sequences, leading to worsening symptoms over generations.
152
What diseases are associated with expanding triplet repeats?
More than 15 diseases are associated with expanding triplet repeats, including myotonic dystrophy and fragile X syndrome.
153
How do expanding triplet repeats cause disease?
Expanding triplet repeats can form abnormal DNA structures that interfere with replication and protein synthesis, leading to cell dysfunction and diseases through a "dominant toxic gain-of-function" mechanism.
154
What is the difference between CNVs and DNA sequence variants?
CNVs involve variations in the number of copies of specific DNA sequences, while DNA sequence variants involve changes in the actual sequence of DNA bases.
155
How do expanding triplet repeats cause myotonic dystrophy type 1?
In myotonic dystrophy type 1, expanding triplet repeats occur in the untranslated region of the gene on chromosome 19, resulting in the production of abnormal mRNA and subsequent cellular dysfunction.
155
How do CNVs contribute to genetic diversity?
CNVs can vary in size and location, potentially affecting gene function or phenotype. They may have no effect, disrupt gene function directly, or indirectly affect neighboring sequences, contributing to genetic diversity and disease susceptibility.
156
What is myotonic dystrophy, and what distinguishes it from other diseases?
Myotonic dystrophy is a genetic disorder characterized by muscle weakness and wasting. It is distinguished by expanding triplet repeats in the DNA sequence, leading to worsening symptoms over generations.
156
What is anticipation in the context of genetic diseases?
Anticipation refers to the phenomenon where symptoms of a genetic disease worsen or appear at an earlier age in successive generations.
157
How do triplet repeat proteins harm cells in expanding repeat diseases?
Triplet repeat proteins harm cells by binding to transcription factors, blocking proteasomes, triggering apoptosis, and interfering with cellular processes, leading to cellular dysfunction and disease.
158
What is myotonic dystrophy type 2, and how does it differ from type 1?
Myotonic dystrophy type 2 is caused by an expanding quadruple repeat of CCTG in a gene on chromosome 3. It differs from type 1 in terms of the affected gene and the nature of the repeat expansion.
159
What is the mechanism behind triplet repeat diseases?
Triplet repeat diseases result from abnormal DNA sequences forming structures that interfere with DNA replication and protein synthesis, leading to cellular dysfunction and disease pathology.
159
What determines the degree to which a mutation alters a phenotype?
The degree of alteration depends on where in the gene the mutation occurs and how it affects the folding, conformation, activity, or abundance of the encoded protein.
160
How do mutations in globin genes affect phenotype?
Globin gene mutations can cause anemia with or without sickling, cyanosis, or increased oxygen affinity. Some variants may have no effect at all.
161
What caused the "blue people of Troublesome Creek" condition?
An autosomal recessive mutation in the CYP5R3 gene, inherited from Martin Fugate, resulted in methemoglobinemia type I, causing excess oxygen-poor hemoglobin and a blue complexion.
162
Explain the difference between hemoglobin S and hemoglobin C mutations.
Both result from mutations affecting the sixth amino acid in the beta globin polypeptide. However, hemoglobin S leads to sickle cell disease, while hemoglobin C does not cause health issues.
163
How is "blue person disease" treated?
Treatment involves administering methylene blue or ascorbic acid to convert methemoglobin back into normal hemoglobin.
164
What factors lessen the negative effects of mutations on phenotypes?
Factors include synonymous codons, which can maintain protein function despite mutations, conditional mutations that only affect phenotype under specific circumstances, and segregation of DNA in stem cell division to protect against mutations in specialized daughter cells.
165
How do synonymous codons protect against mutations?
Synonymous codons may not change the encoded amino acid, preserving protein function, although they can affect mRNA stability and splicing.
166
What is a conditional mutation, and how does it affect phenotype?
A conditional mutation affects phenotype only under certain conditions, providing protection if those conditions are avoided.
167
How does DNA segregation in stem cell division protect against mutations?
Stem cells segregate older DNA strands with mutations into cells that will be shed, minimizing mutations in cells that continually regenerate tissues.
168
What is the significance of conditional mutations in protecting against phenotypic effects?
Conditional mutations only manifest their effects under specific circumstances, potentially safeguarding individuals if they avoid the triggers for symptom expression.
168
What are some effects of mutations in globin genes?
Mutations in globin genes can lead to anemia with or without sickling, cyanosis, or increased oxygen affinity. Some variants may have no discernible effect.
169
How do mutations in the second position of a codon minimize disruption of protein shape?
Mutations in the second position may replace one amino acid with another having a similar conformation, such as GCC mutating to GGC, replacing alanine with glycine.
170
How does the genetic code protect against mutation?
Synonymous codons, where mutations do not change the encoded amino acid, and conditional mutations that only affect phenotype under certain conditions are mechanisms through which the genetic code minimizes the negative effects of mutations.
171
How does methemoglobinemia type I, or "blue person disease," affect affected individuals?
Methemoglobinemia type I leads to excess oxygen-poor hemoglobin, resulting in a blue complexion. Severe cases may cause seizures, heart failure, or death.
172
What mutation causes Clinically silent Hemoglobin (Hb) Wayne?
Single-base deletion in alpha globin gene causes frameshift, changing amino acids 139–141 and adding amino acids.
172
How do stem cells contribute to mutation protection?
During stem cell division, the oldest DNA strands segregate with the stem cell, reducing the likelihood of mutations in specialized daughter cells that will soon be shed.
173
What mutation is associated with Hb Grady?
Nine extra bases add three amino acids between amino acids 118 and 119 of alpha chain.
174
What mutation results in Hb McKees Rocks?
Change from tyrosine to STOP codon at amino acid 145 in beta chain.
174
What mutation leads to Oxygen binding Hb Chesapeake?
Change from arginine to leucine at amino acid 92 of beta chain.
175
What mutation is found in Hb Leiden?
Amino acid 6 deleted from beta chain.
176
Which mutation causes Anemia?
Change from STOP codon to glutamine elongates alpha chain, associated with Hb Constant Spring.
176
What mutation characterizes Hb S?
Change from glutamic acid to valine at amino acid 6 in beta chain causes sickling.
177
Which mutation provides Protection against malaria?
Change from glutamic acid to lysine at amino acid 6 in beta chain causes sickling, associated with Hb C.are all thes
178
Why is DNA repair important for cells?
DNA repair is crucial for cells because mistakes in DNA replication can lead to errors being passed on to daughter cells, potentially resulting in cancer or other genetic disorders.
179
What are the consequences of damage occurring to DNA during replication?
If damage occurs to DNA during replication, the cell may undergo apoptosis (cell death) or attempt to repair the error. If the error is not repaired, it may lead to cancer.
179
How accurate is DNA replication according to the text?
According to the text, DNA replication is very accurate, with only approximately 1 in 100 million bases being incorrectly incorporated.
180
Which components oversee the accuracy of DNA replication?
DNA polymerase and "DNA damage response" genes oversee the accuracy of replication and help in repairing any damage that may occur.
181
Approximately how many times does DNA replicate during an average human lifetime?
According to the text, DNA replicates approximately 10^16 times during an average human lifetime.
182
Which organism is exceptionally efficient at DNA repair?
Deinococcus radiodurans, a large, reddish microbe, is known for being exceptionally efficient at DNA repair. It can tolerate high levels of radiation and can even live in the intense radiation of a nuclear reactor.
183
What contributes to the higher mutation rate of mitochondrial DNA?
Mitochondrial DNA cannot repair itself, which contributes to its higher mutation rate.
184
How does Deinococcus radiodurans repair its DNA?
Deinococcus radiodurans realigns its radiation-shattered pieces of DNA and then uses enzymes to bring in new nucleotides and assemble the pieces.
185
What are thymine dimers and how do they form?
Thymine dimers are extra covalent bonds formed between adjacent pyrimidines, particularly thymines, due to damage from shorter UVB wavelengths.
186
How do organisms repair UV-induced DNA damage caused by thymine dimers?
Organisms repair UV-induced DNA damage caused by thymine dimers through various mechanisms, including photoreactivation and excision repair.
187
What is photoreactivation and how does it enable DNA repair in fungi?
Photoreactivation is a repair mechanism where enzymes called photolyases absorb energy from visible light to detect and bind to pyrimidine dimers, breaking the extra bonds. This enables UV-damaged fungi to recover with exposure to sunlight.
188
Describe excision repair and its significance in DNA repair.
Excision repair is a DNA repair mechanism where enzymes cut the bond between the DNA sugar and base, excising the damaged portion along with surrounding bases. This mechanism plays a crucial role in repairing UV-induced damage and other errors in DNA.
189
What are the two types of excision repair mechanisms in human cells?
The two types of excision repair mechanisms in human cells are nucleotide excision repair and base excision repair.
190
How does base excision repair differ from nucleotide excision repair?
Base excision repair specifically corrects errors resulting from oxidative damage, replacing one to five nucleotides at a time, whereas nucleotide excision repair replaces up to 30 nucleotides and removes errors caused by various factors including chemical carcinogens and UVB radiation.
191
What is mismatch repair and how does it function in DNA correction?
Mismatch repair is a mechanism where enzymes proofread newly replicated DNA for small loops that emerge from the double helix, excising the mismatched base and replacing it with the correct one.
192
How do double-stranded breaks in DNA occur, and how are they repaired?
Double-stranded breaks in DNA can occur due to exposure to ionizing radiation or oxidative damage. They are repaired by multiprotein complexes that reseal the sugar-phosphate backbone either by rejoining the broken ends or recombining with DNA on the unaffected homolog.
193
What is damage tolerance in DNA repair, and how does it differ from other repair mechanisms?
Damage tolerance is a type of DNA repair where a "wrong" DNA base is left in place, but replication and transcription proceed. This differs from other repair mechanisms where the incorrect bases are actively replaced.
194
Why is the ability to repair DNA crucial to health?
The ability to repair DNA is crucial to health because it helps maintain the integrity of the genetic material and prevents mutations that can lead to disorders and diseases.
195
What happens if both copies of a repair gene are mutant?
If both copies of a repair gene are mutant, a disorder can result, potentially leading to increased susceptibility to environmental factors such as toxins and radiation.
196
What is the role of the p53 protein in DNA repair?
The p53 protein, encoded by a well-studied DNA repair gene, controls whether DNA is repaired and the cell salvaged, or if the cell undergoes apoptosis (cell death).
197
How does p53 respond to DNA damage?
Signals from outside the cell activate p53 proteins to aggregate into complexes of four molecules. These quartets then bind to certain genes that slow the cell cycle, facilitating repair. If the damage is too severe, p53 quartets instead increase the transcription of genes that promote apoptosis, leading to cell death.
198
What is the consequence of mutations in repair genes?
Mutations in repair genes greatly increase susceptibility to certain types of cancer following exposure to ionizing radiation or chemicals that affect cell division. This leads to the accumulation of errors in the DNA sequence, perpetuating the development of cancer.
199
Why are DNA repair disorders termed disorders and not diseases?
DNA repair disorders are generally termed disorders rather than diseases because the symptoms do not arise directly from the mutations themselves, but rather from the inability to effectively repair DNA damage.
200
How many genes can cause trichothiodystrophy?
Trichothiodystrophy can be caused by at least five genes.
201
What are the severe symptoms associated with trichothiodystrophy?
Trichothiodystrophy can cause dwarfism, intellectual disability, brittle hair, and scaly skin with low sulfur content.
202
What happens as trichothiodystrophy progresses?
As trichothiodystrophy progresses, growth slows dramatically, signs of premature aging appear, and life expectancy decreases. Hearing and vision may also deteriorate.
203
What causes the symptoms of trichothiodystrophy?
The symptoms of trichothiodystrophy reflect accumulating oxidative damage, which is due to faulty nucleotide excision repair, base excision repair, or both.
204
What is hereditary nonpolyposis colon cancer (HNPCC) also known as?
HNPCC is also known as Lynch syndrome.
205
How do trichothiodystrophies differ from many other conditions?
Trichothiodystrophies are unusual in that they do not increase the risk of cancer despite causing severe symptoms and impairments.
206
What led researchers to link HNPCC to a DNA repair defect?
Researchers linked HNPCC to a DNA repair defect when they discovered different-length short repeated sequences of DNA (microsatellites) within affected individuals.
207
What happens in people with HNPCC?
People with HNPCC experience a breakdown of mismatch repair, which normally keeps microsatellites all the same length.
208
How common is HNPCC?
HNPCC affects 1 in 200 people and accounts for 3 percent of newly diagnosed colorectal cancers.
209
Why is genetic testing advised for all people newly diagnosed with colon cancer?
Genetic testing is advised for all people newly diagnosed with colon cancer because if they have a germline mutation, their relatives can be tested to see if they inherited the mutation as well.
210
What is the recommended course of action for healthy relatives who test positive for the mutation associated with HNPCC?
For healthy relatives who test positive for the HNPCC mutation, frequent colonoscopies are recommended to detect disease early, at a more treatable stage.
211
What is the penetrance of HNPCC by age 70?
The penetrance of HNPCC by age 70 is about 45 percent, indicating a high cancer risk associated with the condition.
212
What precautions must a child with Xeroderma Pigmentosum (XP) take regarding sunlight exposure?
A child with XP must stay indoors in artificial light because even brief exposure to sunlight can cause painful blisters. Failure to cover up and use sunblock can lead to skin cancer, which more than half of all children with XP develop before adolescence.
213
What are the two main mechanisms that can malfunction in XP?
XP can reflect malfunction of nucleotide excision repair or deficient "sloppy" DNA polymerase, both of which allow thymine dimers to stay and block replication.
214
How is Xeroderma Pigmentosum inherited?
XP is inherited in an autosomal recessive manner, meaning it results from mutations in any of seven genes.
215
What is the increased risk of developing skin cancer for individuals with XP?
People with XP have a 1,000-fold increased risk of developing skin cancer compared to others, along with a 10-fold increased risk of developing tumors inside the body.
216
How many individuals in the world are known to have XP?
Only about 250 people in the world are known to have XP.
216
How does a mutation in one of the XP genes lead to multiple disorders?
One of the genes that causes XP, when mutant, can also lead to trichothiodystrophy and another disease, Cockayne syndrome. The different symptoms arise from the different ways that mutations disrupt the encoded protein, which is a helicase that helps unwind replicating DNA.
217
What special arrangements are made for children with XP at a summer camp in upstate New York?
A family in upstate New York runs a special summer camp for children with XP, where night is turned into day. Activities take place at night or in special areas where windows are covered, and light comes from low-ultraviolet incandescent lightbulbs.
218
What is Ataxia Telangiectasia (AT)?
Ataxia Telangiectasia (AT) is a multisymptom condition resulting from a defect in a kinase that functions as a cell cycle checkpoint.
219
What happens in cells affected by AT?
In AT, cells proceed through the cell cycle without pausing after replication to inspect the new DNA and repair any mispaired bases. Some cells undergo apoptosis if the damage is too severe to repair.
220
What is the increased risk of cancer associated with AT?
Individuals with AT have a 50 times higher risk of developing cancer, particularly of the blood. About 40 percent of individuals with AT develop cancer by age 30.
221
What are some additional symptoms of AT?
Additional symptoms of AT include poor balance and coordination (ataxia), red marks on the face (telangiectasia), delayed sexual maturation, and a high risk of infection and diabetes mellitus.
222
How rare is AT, and what is notable about carriers of the AT gene?
AT is rare, but carriers are not. Heterozygotes make up 0.5 to 1.4 percent of various populations. Carriers may have mild radiation sensitivity, leading to a two- to sixfold increase in cancer risk over that of the general population.
223
How can dental or medical X rays affect individuals who are carriers of the AT gene?
For people who are carriers of the AT gene, dental or medical X rays may cause cancer due to their increased radiation sensitivity.
224
What is the consequence of DNA's changeability mentioned in the text?
The changeability of DNA, crucial for the evolution of a species, occasionally leads to harm in individuals. Each person harbors about 175 new mutations, many old ones, and many polymorphisms.
