Gene Mutations Flashcards
What are some of the physical characteristics exhibited by Vincent?
Arched eyebrows, extra-long lashes, bluish eye whites, offset ears, additional teeth, webbed neck, small lower jaw, elastic skin, brittle hair
What developmental and medical conditions does Vincent have?
Developmental delay
Autistic behaviors
Learning disability
How did Marc recognize a syndrome in his son, Vincent?
Marc, having an interest in genetics, recognized a syndrome in Vincent due to his unusual combination of characteristics.
What was the result of the exome sequencing done on Vincent?
Vincent was found to have a de novo mutation in the gene RPS23, which encodes one of the proteins that make up ribosomes.
What organisms did researchers use to study Vincent’s mutation?
Zebrafish and mice were among the model organisms used to study Vincent’s mutation.
How did Marc eventually find other individuals with similar conditions to Vincent?
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.
What was the outcome of using GeneMatcher for Vincent’s case?
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.
What broader impacts did Vincent’s case have on scientific research?
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.
What is a mutation?
A mutation is a change in a DNA sequence that is rare in a population and typically affects the phenotype.
What are the different types of mutations?
Mutations range from substitution of a single DNA base to deletion or duplication of entire chromosomes.
What effects can mutations have?
Mutations may impair a function, have no effect, or even be beneficial, altering protein production, secretion, location, or interaction.
How do mutation, polymorphism, and variant differ?
Mutation refers to rare genetic changes, polymorphism indicates common variations, and variant encompasses both based on frequency and impact.
What is the difference between germline and somatic mutations?
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.
Which parts of the genome can mutations affect?
Mutations can affect sequences encoding proteins or controlling transcription, introns, repeats, and sites critical to intron removal and exon splicing.
Are all DNA sequences equally likely to mutate?
No, not all DNA sequences are equally likely to mutate, with factors such as gene function, environmental influences, and genetic background playing a role.
Can mutations ever be beneficial?
Yes, some mutations can confer advantages, such as resistance to certain diseases, providing insights into evolutionary processes.
How often do somatic mutations occur?
Somatic mutations occur roughly every 300 mitotic cell divisions and are more common in cells that divide frequently.
How is somatic mosaicism clinically relevant?
Somatic mosaicism is implicated in certain genetic diseases, with varying degrees of severity depending on the affected cells.
What challenges arise in genetic testing?
Identifying and interpreting variants of uncertain significance can complicate clinical decisions based on genetic testing results.
Can you provide an example of a beneficial mutation mentioned in the text?
The mutation in the CCR5 gene, which confers resistance to HIV infection, is an example of a beneficial mutation.
Why are some DNA sequences more prone to mutation than others?
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.
How does understanding mutations contribute to medical practice and genetics?
Knowledge of mutations is essential for diagnosing genetic disorders, developing targeted therapies, and understanding evolutionary processes.
What are some broader implications of somatic mosaicism?
Somatic mosaicism plays a role in cancer development, personalized medicine, and our understanding of genetic diversity within individuals.
What are some ethical dilemmas related to genetic testing mentioned in the text?
Ethical challenges include identifying and reporting variants of uncertain significance, protecting patient privacy, and ensuring informed consent in genetic testing procedures.
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.
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.
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.
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.
What was the first genetic illness understood at the molecular level?
Sickle cell disease
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.
What is the DNA level change in sickle cell disease?
A CTC is changed to a CAC, corresponding to RNA codons GAG and GUG.
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.
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.
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.
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.
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.
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.
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.
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.
How many collagen genes encode different types of collagen molecules?
More than 35 collagen genes encode more than 20 types of collagen molecules.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
What disease is associated with mutations in the cystic fibrosis transmembrane regulator (CFTR) protein?
Cystic fibrosis
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.
What are the signs and symptoms associated with cystic fibrosis?
Frequent lung infections and pancreatic insufficiency.
Which protein is affected by mutations in Duchenne muscular dystrophy?
Dystrophin
What are the signs and symptoms of Duchenne muscular dystrophy?
Gradual loss of muscle function.
What is the consequence of deficient LDL receptors in familial hypercholesterolemia?
Accumulation of cholesterol in the blood.
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.
Which protein is affected in familial hypercholesterolemia?
LDL receptor
What are the signs and symptoms associated with familial hypercholesterolemia?
High blood cholesterol levels and early heart disease.
What protein is affected in hemophilia B?
Factor IX
What is the consequence of absent or deficient Factor IX in hemophilia B?
Slow or absent blood clotting.
What are the signs and symptoms of hemophilia B?
Hard-to-control bleeding.
Which protein is affected in Huntington’s disease?
Huntingtin
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.
What are the signs and symptoms of Huntington’s disease?
Uncontrollable movements and personality changes.
What proteins are affected in Marfan syndrome?
Fibrillin or transforming growth factor β receptor
What are the consequences of deficient proteins in Marfan syndrome?
Cataracts in the lenses and aneurysms in the wall of the aor
What are the signs and symptoms associated with Marfan syndrome?
Long limbs, weakened aorta, spindly fingers, sunken chest, lens dislocation.
Which protein is affected in Neurofibromatosis type 1?
Neurofibromin
What is the consequence of defects in neurofibromin protein?
Abnormal growths due to the suppression of activity of a gene that causes cell division.
What are the signs and symptoms of Neurofibromatosis type 1?
Pigmented skin patches and benign tumors of nervous tissue beneath the skin.
What concept is changing the description of single-gene diseases?
Analysis of human genomes is changing the way we describe single-gene diseases.
What were geneticists inconsistent with in the past regarding disease names?
Geneticists were inconsistent when assigning disease names to mutations.
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.
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.
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.
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.
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.
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.
How are researchers reclassifying cystic fibrosis?
Some researchers are reclassifying cystic fibrosis as two allelic diseases based on whether the lungs are affected.
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.
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.
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.
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.
What is the gene associated with Menkes disease and peripheral neuropathy?
ATP7A
What diseases are associated with the DMD gene?
Duchenne and Becker muscular dystrophy
Which gene encodes fibrillin-1 and is associated with Marfan syndrome?
FBN1
What diseases are associated with the FGFR3 gene?
Two types of dwarfism
Which gene is associated with Gaucher disease and Parkinson’s disease?
GBA
What diseases are associated with the PSEN1 gene?
Acne inversa and Alzheimer’s disease
Which oncogene is associated with multiple endocrine neoplasia and Hirschsprung disease?
RET
What diseases are associated with the TRPV4 gene?
Peripheral neuropathy and spinal muscular atrophy
What is a spontaneous mutation?
A spontaneous mutation is one that occurs naturally, often as a result of errors in DNA replication.
What can trigger a spontaneous mutation?
Spontaneous mutations can be triggered by errors in DNA replication, such as the insertion of unstable DNA bases.
