Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

GTEx Project to Expand Functional Studies of Genomic Variation

Published: Wednesday, August 06, 2014
Last Updated: Wednesday, August 06, 2014
Bookmark and Share
Larger set of human tissues to be analyzed to contribute to a database and tissue bank that researchers can use to study how genomic variants influence gene activity.

The National Institutes of Health has awarded eight grants as part of the Genotype-Tissue Expression (GTEx) project to explore how human genes are expressed and regulated in different tissues, and the role that genomic variation plays in modulating that expression. The GTEx awards will contribute to a resource database and tissue bank that researchers can use to study how inherited genomic variants – inherited spelling changes in the DNA code – may influence gene activity and lead to disease. The grants will add data from analyses of tissue samples whose collection began in 2010, as well as expand the resource database and tissue bank.

The research groups will receive approximately $9 million in the first year, and nearly $15 million over three years pending the availability of funds. The project is funded by the NIH Common Fund, the National Institute of Mental Health (NIMH) and the National Heart, Lung, and Blood Institute (NHLBI).

“The new studies complement the current GTEx project in assessing genomic variation and gene expression,” explained Simona Volpi, Pharm.D., Ph.D., GTEx program director in the Division of Genomic Medicine at the National Human Genome Research Institute (NHGRI), which helps administer the program. “They delve deeper into what is happening in tissues on a molecular basis to explain how genomic variation affects how genes work. Ultimately, GTEx will provide an atlas of human gene expression.”

The groups plan to further characterize gene activity in tissues by analyzing several molecular phenotypes, or properties of cells – such as which genes are turned on and off, the various ways genes are regulated and the proteins that cells produce based on such regulation. To do this, scientists will examine part of the more than 30 tissue types available, which were collected through autopsies or organ and tissue transplant programs. The project will eventually include samples from about 900 deceased donors. Researchers will analyze DNA and RNA from the samples to identify and catalog genomic variants and gene expression.

For the last decade, scientists have used genome-wide association studies (GWAS) to study the role that genomic variation plays in complex diseases and traits. In GWAS, researchers compare thousands of genomic variants in individuals with a disease with those without the disease, establishing associations with particular variants and the disease being studied. But understanding what specific genomic variants do and how they influence the development of disease has been much more difficult to pinpoint.

By detailing certain features of cells and tissues, such as methylation patterns, protein levels and other characteristics, Dr. Volpi said that the new studies will “help paint a clearer picture of how genomic variation leads to particular diseases.” In methylation, one way that cells control gene expression is by adding chemicals, such as methyl groups.

“A scientist who is studying asthma or kidney cancer might be particularly interested in studying how genomic variants influence gene expression in the lungs or the kidneys, and the GTEx resource will provide this opportunity,” said Jeffery Struewing, M.D., GTEx program director in the NHGRI Division of Genomic Medicine.

The following research groups have been awarded grants (pending available funds)

University of Washington, Seattle, $1.85 million
Principal Investigator: Joshua Michael Akey, Ph.D.

Somatic mutations – genetic mutations that are not inherited, but instead occur randomly or are caused by environmental factors – can play important roles in many diseases and conditions, especially in cancer. But how these mutations contribute to genetic variability and disease susceptibility is not well understood. 

To find out, Dr. Akey and his coworkers plan to sequence the protein-coding genome regions of more than 15 tissue types and look for variations in DNA sequences and structures. Proteins are the working elements within a cell. They are vital for cellular growth, differentiation and repair. They catalyze chemical reactions and provide defense against disease, among myriad other housekeeping functions. The researchers will develop a comprehensive catalog of somatic mutations, which they hope will aid in identifying and interpreting mutations that cause human disease.

Johns Hopkins University, Baltimore, $3.24 million (including co-funding from NIMH)
Principal Investigator: Andrew Feinberg, M.D., M.P.H.

The investigators plan to analyze DNA methylation patterns across the entire genome, though their main focus is on brain regions that are important in schizophrenia, depression and addiction. Methylation is a process by which cells add chemicals – methyl groups – to genes to control their expression. The work will help researchers understand the relationship between DNA methylation, gene expression and gene sequences in human health and disease.

Massachusetts Institute of Technology, Cambridge, $1.25 million
Principal Investigator: Manolis Kellis, Ph.D. 

Most genetic variants linked to disease don’t code for proteins, but instead have subtle gene regulatory roles, such as altering gene activity levels, or affecting the chemical modifications — epigenomic marks — made to DNA that influence which genes are active in which cells. To better understand the effects of these regulatory variants, researchers plan to characterize the epigenomic effects of genetic variation in nine peripheral tissues with roles in diabetes, heart disease, and cancer. The research will help explain how genetic variation leads to changes in gene expression across tissues, and ultimately how these differences affect a person’s predisposition to disease.

Stanford University, Palo Alto, California, $1.22 million
Principal Investigator: Jin Billy Li, Ph.D.

To gauge the influence of genetic variation on gene regulation and expression in different cells and tissues, researchers can attempt to correlate gene expression with the degree to which a gene is turned on or off. One way to do this is to measure allele-specific expression (ASE). Genes come in pairs, or alleles, and sometimes one allele is expressed to a different degree than the other gene allele. 

Dr. Li, co-investigator Stephen Montgomery, Ph.D., and their colleagues plan to examine ASE in different tissue types to try to better understand the interaction between genetic variants that regulate gene expression and potential disease-causing variants.

University of Washington, Seattle, $2.24 million
Principal Investigator: John Stamatoyannopoulos, Ph.D.

Dr. Stamatoyannopoulos and his group plan to study genetic variants in non-protein coding regions of the genome, where most variants reside. They hope to explore how genetic variation in different types of tissues affects regulatory regions in the genome that control gene activity patterns. To do this, they will use a technique called DNase I-sequencing to examine certain areas in the genome and gauge gene regulation within tissue samples from various ethnic groups.

Stanford University, Palo Alto, California, $2.475 million (including co-funding from NHLBI)
Principal Investigators: Michael P. Snyder, Ph.D., and Hua Tang, Ph.D.

The large-scale project aims to characterize the many different ways in which proteins normally vary, across more than nine tissue types. Scientists will catalog protein variants by mass spectroscopy (a technique to identify chemicals by mass and charge), which will help them understand the genetic basis for protein variation. This will be a valuable resource for researchers to understand the genetic basis of complex traits, and ultimately, in predicting individual disease susceptibility. These research results may also help clinicians design individual prevention and treatment strategies.

University of Chicago, $1 million
Principal Investigator: Barbara Stranger, Ph.D.

Investigators plan to characterize the proteome — the entire set of proteins produced by a genome — in several tissue types to determine the genetic basis of variation in protein expression. They will measure the levels of certain types of proteins that are responsible for sending signals in cells, and another group of proteins that act as switches, affecting which genes are turned on. The researchers will then look for variation associated with differences in protein levels to see if variants associated with protein expression have been previously linked to complex diseases. This may enable them to pinpoint specific proteins or protein networks that may underlie such disease.

University of Chicago, $1.375 million
Principal Investigator: Brandon L. Pierce, Ph.D.

Telomeres are DNA caps at the end of chromosomes that are thought to protect cells from aging. The length of telomeres plays an important role in cell division, growth and genome stability, and evidence suggests that telomere shortening over a lifetime may be involved in disease, including heart disease, dementia and cancer. Interestingly, new research suggests that two common gene variants that lead to longer telomeres may actually increase the risk for deadly brain cancers called gliomas. To better determine the role of telomere length in disease development, Dr. Pierce and his colleagues will ask if telomere length in blood reflects its length in tissues usually associated with cancer, and whether telomere length in specific tissues indicates DNA damage and chromosomes that are unstable. They also will try to gauge the role of variants in genes known to affect telomere length and cancer risk in specific tissues.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
NIH Framework Points The Way Forward For Developing The President’s Precision Medicine Initiative
The NIH Advisory Committee to the Director has presented to NIH Director Francis S. Collins, M.D., Ph.D., a detailed design framework for building a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine.
Monday, September 21, 2015
Beth Israel Cardiology Team Awarded $3 Million by NIH
Work will help predict outcomes in patients with heart disease.
Friday, September 18, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Scientists Uncover Nuclear Process in the Brain that May Affect Disease
NIH-funded study highlights the possible role of glial brain cells in neurological disorders.
Tuesday, August 18, 2015
PINK1 Protein Crucial for Removing Broken-Down Energy Reactors
NIH study suggests potential new pathway to target for treating ALS and other diseases.
Thursday, August 13, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Researchers Identify Protein in Mice that Helps Prepare for Healthy Egg-sperm Union
Protein RGS2 plays a critical role in preserving the fertilizability of the ovulated egg.
Wednesday, August 05, 2015
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Tuesday, August 04, 2015
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
Monday, August 03, 2015
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Monday, July 27, 2015
NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
Scientific News
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Novel Proteins Linked to Huntington's Disease
University of Florida Health researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Long-Sought Protein Sensor for the ‘Sixth Sense’ Discovered
In a study led by scientists from The Scripps Research Institute (TSRI)the sensor protein for propioception has been identified.
How Viruses Commandeer Human Proteins
Researchers have produced the first image of an important human protein as it binds with ribonucleic acid (RNA), a discovery that could offer clues to how some viruses, including HIV, control expression of their genetic material.
Tracking How Herpes Simplex Virus Moves Through Cells
In a recent study, Derek Walsh, PhD, associate professor of Microbiology-Immunology, and his team showed how the herpes simplex virus (HSV) exploits microtubule plus-end tracking proteins to initiate transport and infection in human cells.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos