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

Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Researchers Identify Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Saturday, October 31, 2015
Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Friday, October 23, 2015
Charting Genetic Variation Across the Globe
An international team of scientists has created the world’s largest catalog of human genetic differences in populations around the globe.
Tuesday, October 20, 2015
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Tuesday, October 20, 2015
Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Thursday, October 01, 2015
Scientists Create World’s Largest Catalog of Human Genomic Variation
An international team of scientists from the 1000 Genomes Project Consortium has created the world’s largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why some people are susceptible to various diseases.
Thursday, October 01, 2015
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Tuesday, September 29, 2015
Scientific News
Tardigrade's Are DNA Master Thieves
Tardigrades, nearly microscopic animals that can survive the harshest of environments, including outer space, hold the record for the animal that has the most foreign DNA.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
GMO Food Animals Should be Judged by Product, Not Process
In a world with a burgeoning demand for meat, milk and eggs, regulatory policies around the use of biotechnologies in agriculture need to be based on the safety and attributes of those foods rather than on the methods used to produce them, says a UC Davis animal scientist.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
Gene Drive Reversibility Introduces New Layer of Biosafety
Ability to introduce or reverse the spread of genetic traits through populations could one day improve pest management and disease control.
RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
University of Glasgow Researchers Make An Impact in 60 Seconds
Early-career researchers were invited to submit an engaging, dynamic and compelling 60 second video illuminating an aspect of their research.
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.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
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