Podcast
Questions and Answers
In Angelman syndrome, which of the following molecular mechanisms would least likely result in the presentation of the syndrome?
In Angelman syndrome, which of the following molecular mechanisms would least likely result in the presentation of the syndrome?
- Imprinting defect on the maternal chromosome, causing silencing of the AS gene.
- Deletion of the maternal AS gene region.
- Mutation that causes over-expression of the paternal imprinted gene. (correct)
- Uniparental disomy where both copies of chromosome 15 are inherited from the father.
A child is diagnosed with Prader-Willi syndrome (PWS). Genetic testing reveals that the child has inherited both copies of chromosome 15 from their mother and none from their father. Which of the following molecular mechanisms is the most likely cause of PWS in this case?
A child is diagnosed with Prader-Willi syndrome (PWS). Genetic testing reveals that the child has inherited both copies of chromosome 15 from their mother and none from their father. Which of the following molecular mechanisms is the most likely cause of PWS in this case?
- Paternal deletion
- Uniparental disomy (correct)
- Maternal deletion
- Imprinting defect
A researcher is studying the epigenetic modifications in a cell line. They observe a significant increase in DNA methylation within the promoter region of a particular gene. Which of the following outcomes is most likely to occur?
A researcher is studying the epigenetic modifications in a cell line. They observe a significant increase in DNA methylation within the promoter region of a particular gene. Which of the following outcomes is most likely to occur?
- Unaffected transcription of the gene.
- Decreased transcription of the gene. (correct)
- Increased mutation rate of the gene.
- Increased transcription of the gene.
A geneticist is studying a novel gene that exhibits genomic imprinting. They observe that the gene is only expressed from the maternal allele and is silenced on the paternal allele. Which of the following mechanisms is most likely responsible for the silencing of the paternal allele?
A geneticist is studying a novel gene that exhibits genomic imprinting. They observe that the gene is only expressed from the maternal allele and is silenced on the paternal allele. Which of the following mechanisms is most likely responsible for the silencing of the paternal allele?
A clinical geneticist is counseling the parents of a child newly diagnosed with Angelman syndrome. The genetic testing reveals a deletion in the region of chromosome 15q11.2-q13 that includes the UBE3A gene. What is the most appropriate information for the geneticist to convey regarding recurrence risk in future pregnancies, assuming no other family history?
A clinical geneticist is counseling the parents of a child newly diagnosed with Angelman syndrome. The genetic testing reveals a deletion in the region of chromosome 15q11.2-q13 that includes the UBE3A gene. What is the most appropriate information for the geneticist to convey regarding recurrence risk in future pregnancies, assuming no other family history?
A researcher is investigating potential therapeutic interventions for Prader-Willi syndrome (PWS). Considering the epigenetic nature of the disorder, which of the following approaches would least likely be effective in treating PWS?
A researcher is investigating potential therapeutic interventions for Prader-Willi syndrome (PWS). Considering the epigenetic nature of the disorder, which of the following approaches would least likely be effective in treating PWS?
A patient presents with intellectual disability, seizures, inappropriate laughter, and an ataxic gait. Based on these symptoms, Angelman syndrome is suspected. Which of the following genetic tests would be most useful in confirming the diagnosis?
A patient presents with intellectual disability, seizures, inappropriate laughter, and an ataxic gait. Based on these symptoms, Angelman syndrome is suspected. Which of the following genetic tests would be most useful in confirming the diagnosis?
In a research study, scientists are investigating the effects of a novel drug on genomic imprinting in mice. They treat pregnant mice with the drug and observe that the offspring exhibit altered expression patterns of imprinted genes. Which of the following mechanisms is most likely affected by the drug?
In a research study, scientists are investigating the effects of a novel drug on genomic imprinting in mice. They treat pregnant mice with the drug and observe that the offspring exhibit altered expression patterns of imprinted genes. Which of the following mechanisms is most likely affected by the drug?
A family seeks genetic counseling after their first child is diagnosed with Prader-Willi syndrome (PWS) due to a deletion on the paternal chromosome 15. Both parents have normal chromosome studies. What is the most appropriate explanation of the risk of recurrence for PWS in future pregnancies?
A family seeks genetic counseling after their first child is diagnosed with Prader-Willi syndrome (PWS) due to a deletion on the paternal chromosome 15. Both parents have normal chromosome studies. What is the most appropriate explanation of the risk of recurrence for PWS in future pregnancies?
An investigator is studying the role of non-coding RNAs in epigenetic regulation. They discover a novel microRNA (miRNA) that specifically targets a gene involved in histone methylation. What is the most likely effect of this miRNA on gene expression?
An investigator is studying the role of non-coding RNAs in epigenetic regulation. They discover a novel microRNA (miRNA) that specifically targets a gene involved in histone methylation. What is the most likely effect of this miRNA on gene expression?
Flashcards
Epigenetics
Epigenetics
Mechanisms that change gene expression without modifying the DNA code itself.
Genomic Imprinting
Genomic Imprinting
Silencing of a gene allele depending on parental origin, occurring during gametogenesis.
Deletion
Deletion
The most common molecular mechanism in both Prader-Willi and Angelman syndromes.
Uniparental Disomy (UPD)
Uniparental Disomy (UPD)
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Prader-Willi Syndrome
Prader-Willi Syndrome
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Angelman Syndrome
Angelman Syndrome
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FISH (Fluorescence in situ Hybridization)
FISH (Fluorescence in situ Hybridization)
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Methylation Testing
Methylation Testing
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DNA Methylation
DNA Methylation
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Chromosome or Histone Modifications
Chromosome or Histone Modifications
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Study Notes
Introduction to Epigenetics
- Epigenetics involves mechanisms altering gene expression without changing the DNA sequence
- Epigenetic mechanisms include X-inactivation, chromosome/histone modifications, DNA methylation, and RNA-associated silencing
- X-inactivation randomly silences one X chromosome in females to balance gene dosage
- Chromosome or histone modifications like acetylation, methylation, or phosphorylation affect DNA accessibility for transcription by altering how tightly DNA is wound
Role of DNA Methylation in Gene Expression
- DNA methylation involves adding a methyl group to DNA, often at cytosine bases
- Multiple methylations in a gene's promoter region prevent transcription factor binding, blocking gene expression and leading to decreased gene expression
- Improper methylation can lead to gene silencing and loss of function
Imprinting and Genomic Imprinting
- Imprinting is an epigenetic modification where gene expression depends on whether it's inherited from the mother or father
- During gametogenesis, one allele is silenced, ensuring only one allele of certain genes is expressed based on parental origin
- Imprinting doesn't alter the DNA sequence but uses chemical marks like DNA methylation
- Some genes are expressed only from the maternal allele, while others are expressed only from the paternal allele
Prader-Willi Syndrome and Angelman Syndrome
- Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS) are distinct conditions with different clinical features but a similar molecular basis: genetic deletions or methylation defects
- Each chromosome contains one Prader-Willi gene and one Angelman gene
Molecular Basis of PWS and AS:
- Involves the Prader-Willi gene (expressed from the father's chromosome) and the Angelman gene (expressed from the mother's chromosome)
- Deletion is the most common mechanism: deleting a segment of the chromosome containing a critical gene
- Prader-Willi Syndrome occurs when the paternal gene is deleted, leading to loss of function
- Angelman Syndrome occurs when the maternal gene is deleted or silenced, leading to loss of function
- Imprinting can cause these conditions if one of the alleles is silenced when it should be active
Mechanisms Leading to PWS and AS:
- Prader-Willi Syndrome results from deletion on the paternal chromosome
- If the paternal Prader-Willi gene is deleted and the maternal gene is silenced, the Prader-Willi gene cannot be expressed
- Angelman Syndrome results from deletion on the maternal chromosome
- If the maternal Angelman gene is deleted and the paternal allele is silenced, the Angelman gene cannot be expressed
Additional Causes of PWS and AS:
- Uniparental Disomy (UPD) occurs in 20-25% of cases
- UPD is when both copies of a chromosome are inherited from one parent, while the other parent's copy is missing
- UPD is not an aneuploidy because the total number of chromosomes remains 46
- Imprinting defects occur in UPD cases, causing the affected gene to be silenced because both copies are marked to not function properly
- Example: inheriting both copies of a chromosome from the mother and none from the father leads to a lack of the functioning Prader-Willi gene from the father's side
- Defective imprinting is rare; both paternal and maternal chromosomes are imprinted inappropriately
- Mutations in the genes themselves can lead to ineffective protein production, contributing to the syndromes
Clinical Features of Prader-Willi and Angelman Syndromes
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Prader-Willi Syndrome features intellectual disability, low stature, and hyperphagia, which causes increased overeating and obesity
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Mnemonic: "Father" or "Padre" for the paternal gene loss, emphasizing the loss of the functioning paternal Prader-Willi gene
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There are also small hands and feet, as well as hypogonadism
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Angelman Syndrome features intellectual disability, seizures, and speech development disorders
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Those with Angelman Syndrome express a cheerful demeanor that includes inappropriate laughter and ataxic gait
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Often have a posture where the arms are bent upwards
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Sometimes called the "happy puppet"
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Mnemonic: "Mama’s little angel" for maternal gene loss, highlighting the absence of the functioning maternal Angelman gene
Diagnosis of Prader-Willi and Angelman Syndromes
- FISH (Fluorescence in situ Hybridization) is used to detect deletions on specific chromosomes
- Methylation testing identifies abnormal methylation patterns at the Prader-Willi and Angelman gene loci, helping to confirm the diagnosis
Summary of Key Concepts
- Deletion is the most common cause of both Prader-Willi and Angelman syndromes
- Uniparental Disomy is where both copies of a chromosome are inherited from one parent, leading to imprinting defects
- Imprinting Defects are cases where imprinting marks fail to be established properly
- Clinical features of Prader-Willi Syndrome: intellectual disability, hyperphagia, obesity, short stature, small hands and feet, hypogonadism
- Clinical features of Angelman Syndrome: intellectual disability, seizures, speech delays, cheerful demeanor, inappropriate laughter, ataxic gait
- Diagnosis: FISH and methylation testing are essential for diagnosing these syndromes
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