Epigenetics of Celiac Disease by HC120430175219


									Epigenetics of
Celiac Disease

   Malta 2011
              Why this project?
• Epigenetics is the first level of integration of genetic and
  environmental factors.

• It may translate the effects of risk factors in terms of
  molecular events.

• It is feasable with the recent development of micro
  arrays/Si RNA knowledge.

• There is no data published to date on this topic (pubmed
  september 2011).
        What is epigenetics?
• Epigenetics is the a way to transmit gene
  regulatory signals through mitosis. It is
  required for maintenance of cell

• It is based on
  – DNA methylation
  – Histone acetylation and phosphorylation
  – RNA silencing
Histone acetylation
DNA methylation
RNA silencing
Epigenetics and complex diseases
• Epigenetics is the reflect of
   – Environmental factors
   – Stochastic events
   – Aging

• It is less stable than DNA variations but it is stable
  enough to explain chronic diseases. It may add to or
  reverse the effect of DNA variations explaining
  uncomplete penetrances.

• It may explain
   – Altered sex ratio in complex diseases
   – Incomplete concordance in monozygotic twins
   – Cancers                                    Ptak et al. 2008
             Key questions
• To describe the epigenome of CD (DNA
  methylation and Si RNA expression).

• To integrate this information with genetic
  and environmental data (disease

• To provide disease associated biomarkers
  (predictive markers?).
                  Study design

• 500 CD and 500 controls

• Data collection:
  – Clinical data
  – Environmental factors

• Biobanquing
  – Blood (stored at 20°C)
  – Intestinal biopsies (stored at -20°C).
  – Intestinal biopsies (stored at -80°C in RNA
    later) for few centres.
          Procedures design
• Genetic profiling of participants for the 30
  known CD polymorphisms.

• DNA methylation (Illumina 450k arrays) on
  blood and intestinal samples.

• RNA analyses (siRNA and functional
  validation of DNA methylation data for the
  most relevant genes).

• Biostatistics/ Mathematical modeling.
 Main deliverables/perspectives
• A set of epigenetic biomarkers associated
  with the disease to be tested in
  prospective studies.

• A comprehensive model of
  gene/environment integration at the
  epigenetic level.

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