Genomic Imprinting

1
Genomic Imprinting

• Tradeoffs in communication between maternal and
  paternal genetic effects

2
Genomic Imprinting

• Differential expression of genes depending on
  parental inheritance
• Imprints epigenetic instructions laid down in
  the parental germ cells
• Transfer of nutrients from mother to fetus
• Genetic disorders

3
Evidence

• Uniparental embryos
• Uniparental disomy
• Differences in maternal and paternal
  gene function

4
How does imprinting work?

• DNA methylation
• differentially methylated regions (DMRs)
• Imprinting centers or imprinting
  control elements (ICs)

5
How does imprinting work?
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Methylation and Expression
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Life Cycle of an Imprint
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Evolution

• Found in eutherian mammals, marsupials, and
  flowering plants
• 45 imprinted genes in mouse
• Maternal resources
• maternal-paternal conflicts
• arms races?

9
Imprinting andSignal Detection Theory

• Maternal-offspring communication
• conflicts
• deception/exploitation
• countermeasures

10
Phenotypic effects

• In utero effects
• Insulin and insulin-like growth factors
• Placental growth
• Postnatal effects
• Hyperkinetic/hypokinetic
• Lactation?
• Brain development and function

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Genetic Disorders

• Epimutations
• Prader-Willi syndrome
• Angelman syndrome

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Experiments

• Jena Costs to the mother in expression of the
  imprinted gene Pref1
• Jun Test for polymorphism in imprinted genes
• Tim Uses of genomic imprinting for medical
  diagnoses of neurobehavioral disorders

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Introduction

• Preadipocyte factor 1 (Pref-1)
• adipogenesis differentiation of fat cells
• Functions as a pre-natal growth regulator

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Relation to Genomic Imprinting

• Paternally expressed
• Arms Race
• Based on phenotypic expression
• i.e. size

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Hypothesis

• There is a cost to the mother associated with
  the expression of Pref-1.

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Experimental Design

• Wild-type (/) vs. null (/-)
• Use of knock-out mice
• Differences in size
• Small beneficial for mom
• Large beneficial for dad
• Resource use

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Potential Outcomes

• If cost is found
• This supports Arms Race Theory
• If neutral or beneficial
• Further research is warranted

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The Expression Profiles of IGF2 in the vetebrate
animals

• Test the theory of arm race
• tug-of-war between IGF2 and IGF2R

19
Background for the experiment

• The IGF2 and M6P/IGF2R were the first two
  endogenous genes which contribute embryonic
  growth.
• IGF2 paternal, pro-growth IGF2R maternal,
  anti-growth
• IGF2 signaling is not mediated by M6P/IGF2P, but
  IGF1 receptor or insulin receptor
• The reciprocal imprinting of the two genes show
  tug-of-war
• 80 genes are physically linked in the cluster on
  some chromosomes.
• The functions and linkage of the two genes
  suggest that there is co-evolution. arm race?

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The evolution of the genomic imprinting gene IGF2R

• The gene was found only in the eutherian,
  marsupial but not monotremes
• The IGF2R/M6P shows polymorphism
• IGF2R binding ability to IGF2
• mammalian , marsupial , monotremes-
• Molecular cell, 2000, 5707-716

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Experiment Design

• Choosing the animals
• IGF2 Polymorphism detecting
• Gene expression profiles of IGF2 and M6P/IGF2R
• Gene sequence compare and analysis
• Epimutate the two genes to test their interaction
  
• Test the coevolution theory arm race

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Choosing the animals

• According the evolutionary history
• invetebrate
• Monotremes
• Marsupial
• eutherial

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Polymorphism and expression profile detecting

• RT-PCR reverse transciption PCR
• SNP single-nucleotide polymorphism
• Western Bolt

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Gene sequence compare and analysis

• Cloning and sequencing
• Phylogenetic analysis
• Functional domain and binding domain prediction
  try to give an explanation for the change of the
  binding ability

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Epimutation Analysis

• To test their interaction
• Change the methylation or chromatin pattern
• Interaction?
• IGF2(P) M6P/IGF2R (M)
• IGF2(P) M6P/IGF2R (P)
• IGF2(M) M6P/IGF2R (M)
• IGF2(M) M6P/IGF2R (P)

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Test the theory

• tug-of-war between IGF2 and IGF2R