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

The Genotype-Tissue Expression (GTEx) project consortia, which includes scientists from the Centre for Genomic Regulation (CRG) in Barcelona, have now published their results from their first pilot study in three Science papers. These finding will contribute to a better understanding of genomic variation and give us new clues about disease susceptibility.

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. Thus, every cell “reads” or “switches on” a particular set of genes according to whether it should become a skin, heart, or liver cell. Launched by the 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.

Following their two-year pilot study, GTEx scientists—including scientists from the CRG—have now published their initial results in three articles in the May 8 issue of Science. These breakthrough studies provide new insight into how genomic variants control the how, when, and how many aspects of genes being turned on and off in different tissues, and how this can predispose people to diseases such as cancer, heart disease, and diabetes.

One of these articles investigates the variation of gene expression between individuals and, in particular, between organs and tissues. This research was led by Dr. Roderic Guigó (coordinator of the Bioinformatics and Genomics Programme at the CRG and Professor at the UPF) and involved scientists from the Broad Institute (Harvard University and MIT, Cambridge, Massachusetts) “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,” said Dr. Guigó.

Genes exhibiting high inter-individual expression variation are related to sex, ethnicity, and age. “We 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,” said Dr. Pedro Ferreira, part of the CRG team and currently working at the Institute of Molecular Pathology and Immunology at the University of Porto (Portugal). “We also observed that there are about 2,000 genes, which would represent 10% of human genes, that vary with age, including genes related to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease”, said lead author Dr. Marta Melé, part of the CRG team who is now working at the Harvard University.