A. Roger Little

Neuroepigenomics: resources, obstacles, and opportunities

Long-lived post-mitotic cells, such as the majority of human neurons, must respond effectively to ongoing changes in neuronal stimulation or microenvironmental cues through transcriptional and epigenomic regulation of gene expression. The role of epigenomic regulation in neuronal function is of fundamental interest to the neuroscience community, as these types of studies have transformed our understanding of gene regulation in post-mitotic cells. This perspective article highlights many of the resources available to researchers interested in neuroepigenomic investigations and discusses some of the current obstacles and opportunities in neuroepigenomics.

Meeting Research Needs with Postmortem Biospecimen Donation: Summary of Recommendations for Postmortem Recovery of Normal Human Biospecimens for Research

Normal human tissues, bodily fluids, and other biospecimens of known quality are essential for research to understand the development of cancer and other diseases and to develop new diagnostics and therapies. However, obtaining normal biospecimens appropriate for contemporary large-scale molecular and genomic research is one of the most challenging biospecimen acquisition problems for scientists and biospecimen resources that support research. Recognizing this challenge, the U.S. National Cancer Institute recently convened a series of workshops and meetings focused on the acquisition of normal tissues for research and produced an extensive document, Recommendations for Postmortem Recovery of Normal Human Biospecimens for Research. This article summarizes these recommendations, addressing key ethical, operational, and scientific elements for collecting normal reference biospecimens from postmortem donors in the U.S. Awareness of these recommendations can foster more effective collaborations and mitigate potential logistical challenges, while promoting postmortem biospecimen donation options for families and increasing the availability of high quality normal biospecimens for research. The recommendations have been put into practice in the collection of normal human biospecimens for the NIH Genotype-Tissue Expression Program (GTEx), a pilot study of human gene expression and regulation in multiple tissues which will provide valuable insights into the mechanisms of gene regulation and, in the future, its disease-related perturbations (http://commonfund.nih.gov/GTEx/).

Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease

Genetic variants have been associated with myriad molecular phenotypes that provide new insight into the range of mechanisms underlying genetic traits and diseases. Identifying any particular genetic variants cascade of effects, from molecule to individual, requires assaying multiple layers of molecular complexity. We introduce the Enhancing GTEx (eGTEx) project that extends the GTEx project to combine gene expression with additional intermediate molecular measurements on the same tissues to provide a resource for studying how genetic differences cascade through molecular phenotypes to impact human health.

The NIH NeuroBioBank: creating opportunities for human brain research

The National Institutes of Health (NIH) NeuroBioBank is a federally funded research resource for human neurologic diseases and disorders. This chapter will discuss the principles that guided the creation of the NIH NeuroBioBank and the rationale for the resource model selected. In addition, we will describe some performance metrics in the first 2 years and highlight recent advances in biomedical neuroscience that could only have been achieved using postmortem human tissues. The NIH NeuroBioBank was created in order to increase availability of high-quality postmortem human brain tissues to the research community across a broad spectrum of neurologic diseases and disorders, and to achieve economies of scale over previous funding and organizational models. In addition, we aim to increase public awareness about the value of human tissue donation for research by providing web-based information to the public and through active outreach to disease advocacy communities. Studies with human brain tissue have led to a rapid increase in our knowledge of the biologic differences between humans and are bridging the divide between humans and model organisms. Studies of human brain are beginning to give us a glimpse not only into what makes us uniquely human as well as how individual biology may be connected to health and disease.

Development of a consensus approach for return of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project

The active debate about the return of incidental or secondary findings in research has primarily focused on return to research participants, or in some cases, family members. Particular attention has been paid to return of genomic findings. Yet, research may generate other types of findings that warrant consideration for return, including findings related to the pathology of donated biospecimens. In the case of deceased biospecimen donors who are also organ and/or tissue transplant donors, pathology incidental findings may be relevant not to family members, but to potential organ or tissue transplant recipients. This paper will describe the ethical implications of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project, the process for developing a consensus approach as to if/when such findings should be returned, possible implications for other research projects collecting postmortem tissues and how the scenario encountered in GTEx fits into the larger return of results/incidental findings debate.