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Genomic Imprinting.docx

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Department
Biology
Course
BIOLOGY 2C03
Professor
Bhagwati Gupta
Semester
Fall

Description
October 17 , 2013 Biology 2C03: Genetics Genomic Imprinting Case Study: Genomic Imprinting - Genomic imprinting: epigenetic process that involves DNA methylation and histone modifications in order to achieve monoallelic gene expression without altering the genetic sequence - Epigenetic marks established in the germline and are maintained throughout all somatic cells of an organism - The expression of genes is determined by whether the gene is inherited from the mother or the father - This is an example of an inherited form of DNA modification that alters gene expression or epigenetics - Not changing the nucleotide sequence or the genetic sequence of the DNA - Genomic imprinting: the expression of genes is determined by whether the gene is inherited from the mother or father - This is an example of an inherited form of DNA modification that alters gene expression or epigenetics - Observation:  Igf2 = insulin-like growth factor  Mice inheriting a deletion of this gene from their father were small (60% of normal birthweight)  Mice inheriting the deletion from their mother were normal  Not the sex of the offspring but the sex of the parents that determine whether the phenotype will be expressed  H19 (functional RNA) is expressed only from maternal genome (chromosome inherited by the mom)  Enhancer region producing activator protein which will activate other genes  Insulator is a regulatory element which blocks the enhancer  Not able to interact with Igf2 so it is not expressed  Activator: sister trans-element, protein factor that is moving  Igf2 (insulin-like growth factor) is expressed only from paternal genome  Methylation of the chromosome causes chromosome compaction and does not allow insulator to bind or activate H19  Activator can activate Igf2 transcription  Insulator: regulatory element that blocks enhancers Methylated State is Heritable During Mitosis - Nonmethylated homolog remains nonmethylated - Methylated homolog remains methylated Methylated State is Reset Prior to Meiosis - Epigenetically equivalent - Completely active in primordial germ cells = epigenetically equivalent - Begin to reinitiate the marks of methylation - Methylation reappears based on whether we are producing sperm or oocyte - During fertilization you inherit the specific paternal and maternal marks - IMPORTANT in understanding genomic imprinting is inherited from the parents and not dependent on the offspring What Might happen if there is No Methylase? - No methylase: H19 would be produced as the enhancer does now travel to Igf2 What Phenotypic Effect can this have? - Deletion inherited from mother:  Normal levels of Igf2 expres
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