A new light shed on genetic regulation's role in the predisposition to common diseases

September 2, 2012

An international team of researchers from King's College, Oxford University, Wellcome Trust Sanger Institute and Faculty of Medicine of University of Geneva, has discovered several thousands new genetic variants impacting gene expression some of which are responsible for predisposition to common diseases, bringing closer to the biological interpretation of personal genomes.

Genetic disease risk differences between one individual and another are based on complex aetiology. Indeed, they may reflect differences in the genes themselves, or else differences at the heart of the regions involved in the regulation of these same genes.

By we mean the decision that the cell makes as to when, where and at what level to activate or suppress the expression of a gene. In theory, two people could thus share a gene that is perfectly identical and yet show differences in their predisposition to a disease due to concerning the regulation (overexpression or underexpression) of this same gene.

Numerous teams are currently trying to draw up a map of regions involved in gene regulation. Not an easy task, but invaluable since it allows us to understand all the that can explain the predisposition to certain diseases.

Working with twins

Emmanouil Dermitzakis, Louis-Jeantet Professor at the Faculty of Medicine and member of the NCCR Frontiers in Genetics and the Institute of Genetics and Genomics of Geneva (IGE3), is a specialist in what is called the genetics of complex traits. With an international team co-led by Professor Tim Spector (Kings College), Professor Mark McCarthy (Oxford University) and Dr. Panos Deloukas (Wellcome Trust Sanger Institute), he publishes a study highlighting thousands of these genetic variants that seem to explain individual differences in .

For this work, the researchers used samples of three different tissue types (adipose tissue, skin and ) collected from more than 800 homozygotic (identical) and dizygotic twins.

"Identifying variants which control the activity of many genes is a greater challenge than we anticipated but we are developing appropriate tools to uncover them and understand their contribution to disease," comments Panos Deloukas. "Modern human genetics combined with samples donated by the participants in studies such as TwinsUK is making great strides towards finding the genetic culprits behind human disease."

The method researchers followed allowed them to uncover nearly 358 variants apparently involved in the predisposition to certain diseases including quantifying the contribution of rare regulatory variants that was previously not possible to identify by conventional analysis methods.

"Our work adds to those who have previously demonstrated the contribution of common variants in the predisposition to these disorders", explains Emmanouil Dermitzakis. "Thanks to this new level of knowledge, and if we manage to adapt this methodology to search for these variants in each individual, this will be a powerful tool to help prognose the to certain diseases and more importantly understand the biological aetiology in order to develop and employ individualized treatments."

Explore further: New approach to link genome-wide association signals to biological function

Related Stories

New approach to link genome-wide association signals to biological function

June 30, 2011
Researchers have developed a new strategy to improve the outcome of genome-wide association (GWA) studies.

When is a gene not a gene? New catalog helps identify gene variations associated with disease

February 16, 2012
A high-quality reference catalogue of the genetic changes that result in the deactivation of human genes has been developed by a team of researchers. This catalogue of loss-of-function (LoF) variants is needed to find new ...

Mouse genetic blueprint developed

September 14, 2011
Researchers have developed a valuable mouse genetic blueprint that will accelerate future research and understanding of human genetics. The international team, led by researchers at the Wellcome Trust Sanger Institute and ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.