NIH will expand existing gene expression resources to include developmental tissues

Eleven years ago, researchers at the National Institutes of Health (NIH) saw a gap in the availability of high-quality tissue samples and information on gene expression — important resources that scientists needed to understand how differences in our genes directly affect the makeup and function of our bodies.

In response to this realization, they began the Genotype-Tissue Expression (GTEx) consortium, which successfully obtained high-quality tissue samples from over 900 adult postmortem donors. It also established a resource for researchers to explore gene expression in many different tissues to understand the impact of genomic variation on complex traits and diseases.

 But gaps in our knowledge still remain as gene expression varies at time points in an individual’s life and is largely unstudied in childhood. However, the database and tissue bank established by GTEx only includes tissue samples from adult postmortem donors. Researchers require information on developmental body tissues not only to understand how gene expression is regulated over time from birth to adulthood, but also to help children who are currently living with genomic diseases.

To work toward completing the resource, NIH will award $38.5 million over five years to the Developmental Genotype-Tissue Expression (dGTEx) project, which aims to build a widely available tissue bank and database with information about human developmental gene expression in many types of tissues from children for use in basic and clinical research.

“There’s still so much we don’t know about how our gene expression evolves and changes over time,” says Jyoti Dayal, M.S., a program director in the National Human Genome Research Institute (NHGRI) Division of Genomic Medicine. “We hope this project will lend more insight into how our genes are expressed at each stage in our lives.”

Multiple types of tissues from at least 120 postmortem pediatric donors will be collected for the study. Analyzing these samples will help researchers understand gene expression and function through different stages of development in the pediatric population. 

There is often a shortage of “normal” tissue against which to compare tissues donated from children with pediatric diseases. Knowledge gained from this database could potentially provide hope for children with some of those diseases.

There’s still so much we don’t know about how our gene expression evolves and changes over time. We hope this project will lend more insight into how our genes are expressed at each stage in our lives.

“It’s tragic when children die, but this type of project actually can provide meaning for grieving families," says Melissa Parisi, M.D., Ph.D., chief of the Intellectual and Developmental Disabilities Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

NHGRI will fund two awards, and NICHD will fund one award, each contributing a total of $14.25 million to the project over five years. In addition, the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH) will each contribute $5 million to fund the procurement and genomic analyses of developmental brain tissues.

The NICHD award will establish a Biospecimen Procurement Center that will collaborate with organ donor organizations and medical examiners to identify the pediatric donors. It will also support research on the ethical, legal and social implications of collecting tissues from deceased pediatric donors to explore the impact of tissue donation and genetic analysis on the families of the donors. 

The two NHGRI awards will establish Laboratory, Data Analysis and Coordinating Centers (LDACC) modeled closely after the adult GTEx project. These centers will perform the genome sequencing and analyze gene expression in tissues that the Biospecimen Procurement Center collects. The LDACC centers will also oversee and manage the project. 

“The resource created by the dGTEx project could have huge implications for genomic medicine as we understand the changes that occur during human development,” says John Ilekis, Ph.D., a program director in the pregnancy and perinatology branch at NICHD.

The newly awarded study sites include:

• Thomas Bell, Ph.D., National Disease Research Interchange, Philadelphia (funded by NICHD, NINDS, NIMH)

• Kristin Ardlie, Ph.D., Broad Institute, Cambridge, Massachusetts (funded by NHGRI)

• Nenad Sestan, M.D., Ph.D., Yale University, New Haven, Connecticut (funded by NHGRI, NINDS, NIMH)