SEP 11, 2020 8:45 PM PDT

How Variants Affect Gene Expression Across Cell Types

WRITTEN BY: Carmen Leitch

A multitude of peer-reviewed studies has come out of the Genotype-Tissue Expression (GTEx) Consortium, a multi-institutional effort that aims to shed new light on various aspects of human genetics. One recent study from the consortium members examined how small changes in the genome, or genetic variants, affect the activity of a gene. Another paper examined a person's risk of developing certain diseases or characteristics because of such variants it is one of fifteen studies involving GTEx that have been recently reported in Science.

Image credit: Pixabay

The GTEx dataset was generated from RNA sequencing, which provides a snapshot of the genes that are active in a cell. It was performed on 49 post-mortem tissues collected from 838 volunteers: 15,201 RNA-sequencing samples in all.

This final set of studies completes the GTEx project, and now there is an atlas of genetic variants that influence gene expression, cellular changes that may be occurring due to these variations, and how they affect the risk of developing both common and rare diseases.

Since many genetic variants that have been associated with an increased risk of disease do not sit in portions of the genome that code for protein, it's been suggested that these disease risk-associated variants are acting by changing gene regulation. GTEx has helped provide some insight into this hypothesis.

"This study is a crowning collaborative achievement, in which dozens of scientists combined their expertise to build a map of genetic regulatory variation and to understand the core biology of genetic variation," said Dr. Tuuli Lappalainen, Ph.D., Core Faculty Member at the New York Genome Center. "GTEx resources also empower other studies by the genomics community, including disease-specific research, the identification of targets for drug development, and understanding genome function."

The researchers applied a tool called expression quantitative trait locus (eQTL) analysis to find changes in the genetic sequence, or variants, which affect the expression of a gene. They included QTLs that affect how RNA is spliced, which creates different instructions for making a protein. This approach has identified eQTLs and sQTLs for most human genes that are expressed in 49 tissues. The GTEx data was integrated with genome-wide association studies to gain insight into the mechanistic changes induced by alterations in regulation or splicing that promote disease development.

Another GTEx study reported in Science assessed how genetic variants affect gene expression levels in different tissue types. "Our approach allowed mapping genetic variants that affect gene regulation in different cell types for a large number of tissues. This enables better discovery of mechanisms behind genetic variants that affect disease risk," said Sarah Kim-Hellmuth, M.D., Ph.D., a former Postdoctoral Fellow in the Lappalainen lab and first study author.

Sources: AAAS/Eurekalert! via New York Genome Center, Science

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 16, 2020
Microbiology
Newly Discovered Gut Enzyme Could Function as Disease Biomarker
AUG 16, 2020
Newly Discovered Gut Enzyme Could Function as Disease Biomarker
Bacteria in the gut have a powerful influence on our health, in part because all of those microbes have genes of their o ...
SEP 05, 2020
Cardiology
Psoriasis and Hyperlipidemia May Put You at Risk for Chronic Kidney Disease
SEP 05, 2020
Psoriasis and Hyperlipidemia May Put You at Risk for Chronic Kidney Disease
The sad truth is that many diseases not only carry their own symptoms but can also increase the risk of the onset of ano ...
SEP 14, 2020
Health & Medicine
Direct Amplification: Rapid, Extraction-Free RT-qPCR Results
SEP 14, 2020
Direct Amplification: Rapid, Extraction-Free RT-qPCR Results
As the SARS-CoV-2 pandemic continues to rage across the United States and around the globe, the demand for COVID-19 test ...
SEP 13, 2020
Cell & Molecular Biology
RNA Found on the Surface of Human Cells
SEP 13, 2020
RNA Found on the Surface of Human Cells
The surface of a cell carries many features to help it carry out its functions, communicate with other cells, gather inf ...
SEP 20, 2020
Cell & Molecular Biology
Revealing the Structure of Hallucinogens Bound to Their Receptor
SEP 20, 2020
Revealing the Structure of Hallucinogens Bound to Their Receptor
Recent studies have demonstrated that hallucinogenic drugs like LSD, psilocybin, and mescaline have therapeutic potentia ...
OCT 22, 2020
Cell & Molecular Biology
How a Gene Variant Raises the Risk of Multiple Sclerosis
OCT 22, 2020
How a Gene Variant Raises the Risk of Multiple Sclerosis
Now that sequencing the whole human genome is easier, faster, and cheaper than it used to be, scientists have been able ...
Loading Comments...