Epigenetic Reprogramming
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Questions and Answers

What is the outcome of genomic imprinting?

  • Expression of genes from only one parental chromosome homologue (correct)
  • Expression of genes from neither parental chromosome homologue
  • Expression of genes from both parental chromosome homologues
  • Random expression of genes from both parental chromosome homologues

    • How do imprinted genes differ from non-imprinted genes?

  • They are regulated by genetic differences
  • They are often involved in placental and embryonic development (correct)
  • They are always inherited from the mother
  • They are expressed from both parental chromosome homologues

    • What is the function of an imprinting control region (ICR)?

  • To establish epigenetic marks in the germline
  • To regulate the expression of multiple imprinted genes in a cluster (correct)
  • To regulate the expression of a single imprinted gene
  • To prevent the expression of imprinted genes

    • What is the cause of imprinting disorders?

    <p>All of the above</p> Signup and view all the answers

    What is the outcome of UPD?

    <p>Inheritance of both copies of a chromosome from the same parent</p> Signup and view all the answers

    Why do familial cases of imprinting disorders arise from mutation rather than from chromosomal nondisjunction and UPD?

    <p>DNA methylation is reset between generations</p> Signup and view all the answers

    What is the relationship between environmental factors and the genome?

    <p>Environmental factors can cause epigenetic changes</p> Signup and view all the answers

    What is a challenge in determining whether an observed epigenetic change is causal or secondary to the phenotype?

    <p>Both a and b</p> Signup and view all the answers

    What is the outcome of the two waves of epigenetic reprogramming?

    <p>Erasure and re-establishment of epigenetic marks</p> Signup and view all the answers

    Why is it important to understand mechanisms conferring non-genetic effects?

    <p>To understand the mechanisms underlying disease</p> Signup and view all the answers

    What is the term for the critical level of mutant mtDNA in a cell that must be exceeded before a biochemical effect is detected?

    <p>Threshold Effect</p> Signup and view all the answers

    Why is the level of heteroplasmy not fixed in an individual?

    <p>Because mitochondrial DNA replicates stochastically</p> Signup and view all the answers

    What is the term for the random distribution of mitochondria to daughter cells during cytoplasmic division?

    <p>Stochastic segregation</p> Signup and view all the answers

    Why do the levels of heteroplasmy vary widely between mother and child?

    <p>Because of the bottleneck effect</p> Signup and view all the answers

    What is the term for the phenomenon where a person with a mtDNA mutation does not show the associated phenotype?

    <p>Reduced penetrance</p> Signup and view all the answers

    What is the environmental factor that triggers the hearing loss phenotype in individuals with the mtDNA mutation?

    <p>Aminoglycoside antibiotics</p> Signup and view all the answers

    Which tissues are primarily affected by mitochondrial disorders?

    <p>Muscle and brain</p> Signup and view all the answers

    What is the name of the technique allowed by the UK government in 2015 to prevent the transmission of mitochondrial disease?

    <p>Mitochondrial therapy</p> Signup and view all the answers

    Why are mitochondrial diseases genetically and phenotypically diverse?

    <p>Because of the interaction with the nuclear genome and environment</p> Signup and view all the answers

    What is the purpose of the bottleneck effect in germline development?

    <p>To randomly sample the mitochondrial population</p> Signup and view all the answers

    When do epigenetic marks in male germline cells typically get established?

    <p>During foetal development</p> Signup and view all the answers

    What mechanism is not involved in the erasure of epigenetic marks after fertilisation?

    <p>Genetic inheritance</p> Signup and view all the answers

    Which type of cell marks the beginning of epigenetic reprogramming in primordial germ cells?

    <p>Prospermatogonia</p> Signup and view all the answers

    Which cells are marked by new epigenetic patterns in females after birth?

    <p>Growing oocytes</p> Signup and view all the answers

    What is the ultimate goal of resetting DNA to a stem cell state post-fertilization?

    <p>To produce all cell types needed for the embryo and extraembryonic tissue</p> Signup and view all the answers

    What are genomic imprints resistant to?

    <p>Second wave of epigenetic reprogramming</p> Signup and view all the answers

    Which process is involved in the progressive re-establishment of epigenetic marks around the time of implantation?

    <p>Gene regulation for early embryonic lineages</p> Signup and view all the answers

    What best describes the inheritance of epigenetic information?

    <p>Not inherited through generations</p> Signup and view all the answers

    What is a known effect of undernourishment of the embryo in utero in mice?

    <p>Developmental delay</p> Signup and view all the answers

    In what generation would effects need to be observed for an environmentally-induced trait to be considered a true inherited transgenerational effect?

    <p>F3</p> Signup and view all the answers

    Which historical event provides data on how in utero nutritional compromise can lead to adult onset disease in humans?

    <p>The Dutch Hunger Winter</p> Signup and view all the answers

    How many genes does the mitochondrial genome contain?

    <p>37</p> Signup and view all the answers

    Which hypothesis suggests how the mitochondrial genome arose?

    <p>Endosymbiont Theory</p> Signup and view all the answers

    How is mitochondrial DNA inherited?

    <p>Maternally</p> Signup and view all the answers

    What happens to sperm mitochondria upon fertilization?

    <p>They are degraded</p> Signup and view all the answers

    What is the term for cells containing a mixed population of normal and mutant mtDNAs?

    <p>Heteroplasmy</p> Signup and view all the answers

    What type of transcript is generated from a single promoter in mitochondrial genomes?

    <p>Multigenic</p> Signup and view all the answers

    What characterizes the mitochondrial genome compared to the nuclear genome?

    <p>All but 1kb of it makes a functional gene product</p> Signup and view all the answers

    Study Notes

    Epigenetic Reprogramming

    • Epigenetic information is not inherited from one generation to the next, unlike genetic information.
    • During germ cell development, epigenetic marks are erased early in primordial germ cell (PGC) development, allowing new marks to be established.
    • In the male germline, epigenetic marks are established during fetal development, while in the female germline, marks are established after birth, during the growing oocyte phase.
    • There are two phases of genome-wide epigenetic erasure and re-establishment: the first occurs during germ cell development, and the second occurs immediately after fertilization.

    Genomic Imprinting

    • Genomic imprints are DNA methylation marks that are established in different places in the male and female germlines and are resistant to epigenetic reprogramming.
    • These imprints allow for the retention of a memory of parental origin on chromosomal regions containing imprinted genes.
    • Imprinted genes are often involved in placental and embryonic development, as well as postnatal metabolism and behavior.
    • The monoallelic expression of an imprinted gene is regulated by DNA methylation that differs on the two parental chromosomes.

    Imprinting Disorders

    • Imprinting disorders arise from the mis-expression of imprinted genes and can be caused by mutation, uniparental disomy, or epimutation.
    • Epimutation causes the imprinting control region (ICR) to lose its appropriate differential methylation status, leading to abnormal imprinting.
    • Most cases of imprinting disorders are sporadic, but occasionally they can be passed on in families and show parental origin effects in their pattern of inheritance.

    Transgenerational Epigenetic Inheritance

    • There is evidence that the environment can influence phenotype in ways that do not appear to arise from genetic mutation.
    • However, it is challenging to determine whether an observed epigenetic change associated with an environmental influence is causal or a secondary consequence of the phenotype.
    • Studies have shown that the environment a conceptus is exposed to in utero can have an influence on adult onset diseases after birth.
    • However, it remains unclear whether an environmentally-induced trait can be inherited across generations.

    Mitochondrial Inheritance and Disease

    • The mitochondrial genome is 16.5kb, circular, and contains 37 genes with no introns.
    • Mitochondrial genetics displays unusual features, including matrilineal inheritance and the ability to have a mixed population of normal and mutant mtDNAs (heteroplasmy).
    • Mitochondrial disorders can show reduced/incomplete penetrance of the phenotype in individuals with the same mutation due to factors such as variable levels of heteroplasmy and interactions with the nuclear genome and environment.
    • Mitochondrial replacement therapy (MRT) has been approved in the UK and involves the transfer of nuclear genetic material into a donor egg containing healthy mitochondria to generate a healthy baby free of mitochondrial disease.

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    Description

    Learn about the process of epigenetic reprogramming, where epigenetic marks are erased and re-established during germ cell development.

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