NIH-funded Genotype-Tissue Expression (GTEx) project describes how differences in DNA affect gene activity, disease onset


GRAND RAPIDS, Mich. (May 26, 2015)—Van Andel Research Institute (VARI) is playing a key role in a National Institutes of Health (NIH)-funded project to establish a resource to describe how differences in an individual’s genetic makeup affect gene expression and regulation.

The Institute’s Biorepository serves as the Comprehensive Biospecimen Resource for the Genotype-Tissue Expression (GTEx) project, a multi-institutional effort that provides scientists with a comprehensive database to better study the relationships between an individual’s genetic makeup, or genome, and tissue-specific gene expression. The project sheds light on how differences in the genome affect which genes are turned on or off and to what degree, and how these variations may contribute to disease onset and progression.

VARI’s Biorepository has an integral role in biospecimen collection for the project, including developing and shipping the kits used by investigators around the country to collect tissue samples. Collaborators at these Biospecimen Source Sites are collecting up to the 35 different sample types from 900 organ, tissue and autopsy donors, and then sending the samples to VARI for processing and biobanking. From there, tissue samples are sent to the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University for nucleic acid isolation, and DNA and RNA sequencing. Electronic images of microscope slides also are sent for evaluation to pathologists at the National Cancer Institute (NCI), part of NIH. Investigators from around the world are participating in the data analysis.

The data garnered from the samples are available to qualified researchers through the database of Genotypes and Phenotypes (dbGaP) at the National Library of Medicine, NIH. Biospecimens from the project also are available to qualified researchers. Additional information is available online at www.gtexportal.org and www.genome.gov/gtex.

“In the future, as medicine further harnesses the power of an array of genomic profiles, we’ll look back on the GTEx project as an integral step on the road to enhancing personalized medicine,” said Scott Jewell, Ph.D., director of VARI’s Biorepository. “These data are an absolutely invaluable resource for scientists studying the origins of disease as well as working to develop new treatments for conditions like cancer, neurodegenerative diseases and cardiovascular diseases, among others.”

VARI’s work on GTEx is funded by NCI and NIH, with overall funding for GTEx provided by the NIH Common Fund. VARI was selected as the Comprehensive Biospecimen Resource for NCI in 2010 after a rigorous and competitive application process. The Institute’s Biorepository is nationally and internationally recognized, and is accredited through the College of American Pathologists.

“The NIH-GTEx program has truly been a collaborative effort from start to finish,” Jewell said. “The spirit of teamwork was evident not only within the GTEx Consortium, but also within our own Institute, from the biospecimen and pathology teams to grant support, logistics, operations and security. It was an all-hands-on-deck process and I’m extremely proud of the work we’ve accomplished.”

The first papers from the project were published May 7 in Science, and May 8 in Bioinformatics, PLoS Computational Biology and Genome Research. In one of the three papers published in Science, scientists analyzed gene expression data from more than 1,600 tissue samples derived from 43 tissue types from 175 individuals. Although all of an individual’s cells have the same set of genes, which genes are expressed and to what degree varies across tissues. By analyzing these differences, scientists found certain groups of genes that had the same effect regardless of tissue type as well as subtypes of genes that exhibited tissue-specific effects. Investigators also found that although certain genes may be expressed across multiple tissue types, they can be up- or down-regulated differently among tissues depending on local genetic variation.

“The project allows us a unique look at gene expression and regulation across individuals and tissues at the same time,” said Kristin Ardlie, Ph.D., principal investigator of the Laboratory, Data Analysis, and Coordinating Center at Broad Institute and corresponding author on two of the Science papers. “It’s a tremendous undertaking to obtain these valuable samples, yet the teams involved, such as VARI, have made it appear seamless.”

GTEx was launched in 2010, and is managed by the National Human Genome Research Institute, NCI, the National Institute of Mental Health, and the NIH Common Fund.


Van Andel Institute (VAI) is an independent biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 270 scientists, educators and staff. Van Andel Research Institute (VARI), VAI’s research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson’s and other diseases and translating those findings into effective therapies. The Institute’s scientists work in on-site laboratories and participate in collaborative partnerships that span the globe. Learn more about Van Andel Institute or donate by visiting www.vai.org. 100% To Research, Discovery & Hope®


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