Epigenetics of Human Health and Disease

Summary

The study of epigenetics/epigenomics has garnered much attention in the biological research community recently. The National Institutes of Health (NIH) took the opportunity to hold a workshop on March 18-19, 2007, to examine the possibility of supporting a project to further understand the field of epigenetics/epigenomics, potentially through the NIH Roadmap program. The workshop brought together national and international experts in the field, as well as NIH staff interested in further exploring the field.

After presentations of current views of and activities relating to epigenetics/epigenomics, the participants discussed possible scientific strategies and addressed potential challenges relevant to an Epigenomics Project. The group covered such topics as: application to human health and disease, identification of tools and resources, technology and bioinformatic development, and data analysis requirements. Overall, the participants endorsed the concept of an NIH-supported Epigenomics Project because of its potential for providing significant insights into the relationship between epigenetic mechanisms and their affect on human health and disease.

The recommendations from the workshop are summarized as follows:

Application to Human Health and Disease

Obtain a comprehensive map of the epigenome, comparing undifferentiated stem cells to differentiated cells. Understanding the epigenetic basis of stem cells will determine what makes a stem cell different from a somatic cell and will be needed to understand the molecular basis of tissue types, as well as the molecular basis of pluripotency and phenotypic variation among tissue types.

The long term goal is to lay a foundation for understanding epigenetic alterations associated with human health and disease, illuminating the pathway on which the epigenetic basis of normal development, common disease, susceptibility, and environmental exposure can be explored. Many complex diseases remain intractable, as do the nature of environmental influences on human health. The integration of epigenetics with genetics provides the promise for new avenues for discovery.

Tool and Resources

Develop an epigenetics toolbox including existing/new tools (standardized protocols, platforms, reagents, antibodies, and wiki-site) and resources (genetically engineered model systems, biological materials, and clinical samples that will be acquired through existing NIH investigative groups [CTSAs and tissue banks]). Compile/inventory the available tools nationally and internationally and identify the needs. Define the performance standards (quality, reproducibility, validity, sensitivity, specificity, etc). Focus on antibody acquisition/production, genetically engineered model systems, and access to banks of human cells/tissue (renewable resources that are key to these experiments).

Facilitates access and availability of standardized tools would enable investigators to measure epigenetic and epigenomic changes, facilitating the construction of reference epigenomes and application of epigenetic marks to several diseases. This base should provide the expertise to evaluate the epigenome of a single cell, leading to diagnosis, prevention (risk assessment/stratification), and management of disease, based on epigenetic marks. The overall goal is to provide the tools and resources that move epigenetics from the bench to the clinic.

Technology / Bioinformatics Development

Develop tools, probes, reagents, and/or technology that would allow remote imaging of epigenetic activity in tissues or whole animal. This would allow for identification of measurable targets, pathways, and markers, and ultimately lead to imaging of cells or complex tissues in humans to scan for specific analytes relevant to epigenetics.

Form a consortium of biologists to collect data and informaticians to develop algorithms, to build the infrastructure (maps and algorithms) needed to model epigenetic processes and incorporate epigenetic information in genetic studies. Develop methods to integrate the various types of epigenetic and genetics data. Current studies, such as the twin studies, could be leveraged for additional epigenomic data. The ultimate goal is to begin to model epigenetic processes and their effect on genetics of disease.

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