08:50am Thursday 19 October 2017

Gene expression is key to understanding differences between individuals and predisposition to disease

Although the genetic blueprint of every cell is the same, each cell has the potential to become specific for a tissue or organ by controlling its gene expression. Scientists involved in the GTEx project have been working for two years on a pilot study described in three papers published in Science. Miquel Calvo points out that the UB research group has contributed to “the development of a new method for the statistical treatment of project’s transcriptomics data”.

One of these articles investigates the variation of gene expression between individuals and, in particular, between organs and tissues. “We realized that gene activity differed much more across organs or tissues than across individuals. Variation between individuals accounted only for about 5% of the total variation in gene activity”, explains Roderic Guigó, researcher in the Centre for Genomic Regulation (CRG) and professor at the Pompeu Fabra University, who led the article.

Surprisingly, the relationship between gene expression and tissue specificity was found to be less straightforward than expected. For example, considering that cells are more similar within each tissue type, scientists expected to find gene expression patterns that are tissue-specific. However, Ferran Reverter, professor in the Department of Statistics of the UB and CRG researcher, affirms that “even though tissues and organs have a specific gene expression pattern, we have found surprisingly few genes expressed exclusively in a particular tissue or organ”.

Genes exhibiting high inter-individual expression variation are related to sex, ethnicity, and age. Experts have found differences linked to sex in more than 750 genes, with the vast majority in breast tissue. In the same way, gene expression differences between individuals with African or European roots are concentrated in the skin. It has been also observed that there are about 2,000 genes, which would represent 10% of human genes, which vary with age, including genes related to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease.

The GTEx project, a step forward to understanding the human genome

Launched by the North-American National Institutes of Health (NIH) in 2010, the GTEx project aims to create a reference database and tissue bank for scientists to study how genomic variants affect gene activity and disease susceptibility. Researchers have collected more than 30 tissue types from autopsy or organ donations and tissue transplant programs and are analysing both DNA and RNA from these samples. The project is supported by the NIH and administered by the National Human Genome Research Institute (NHGRI), the National Institute of Mental Health (NIMH), and the National Cancer Institute (NCI).

“The number of tissues examined in GTEx provides an unprecedented depth of genetic variation. It gives us unique insights into how people differ in gene expression in tissues and organs from both genomic and environmental causes”, highlights Emmanouil Dermitzakis, professor of Genetics at the University of Geneva Medical School (Switzerland) and one of the project leaders.


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