Major European study reveals role of genes in disease

EUMODIC consortium studies functions of over 300 mouse genes

DOI: 10.1038/ng.3360

Large scale study analysed the role of over 300 mouse genes. [DOI: 10.1038/ng.3360]

The role of over 300 mouse genes have been analysed by scientists across Europe in a major initiative to try to understand the part they play in disease and biology.

Since mice share over 90 per cent of their genes with humans they represent one of the best organisms to help us understand human genetics. The European Mouse Disease Clinic (EUMODIC), a consortium that includes the Wellcome Trust Sanger Institute, brought together scientists from across Europe to investigate the functions of 320 genes in mice. These studies involved generating individual mouse lines in which a single gene had been turned off. Over half of these genes had no previously known function and the remaining genes were poorly understood.

Over 80 per cent of the mouse lines assessed had a characteristic that provided a clue to what the missing gene’s role might be. If the mouse failed a hearing test, for example, the suggestion was that the missing gene might have a role in hearing. In total, they carried out over 20 different tests capturing data on 400 characteristics for each mouse line.

“The standardised practices that have been developed through this research allow multiple centres to work in concert to generate robust, reproducible data. In the long term, this streamlined approach and the availability of the data from these studies will significantly reduce the number of animals used in research.”

Dr David Adams Senior Group Leader at the Sanger Institute, a major contributor to the EUDOMIC Consortium

The researchers classified 94 genes out of the 320 studied that were linked to disease into three categories: bone and skeleton, metabolism, and neurological and behavioural disorders.

One of the genes studied, Elmod1, belongs to a large group of genes active in the brain for which no information on function is available. This work revealed that mice with a faulty Elmod1 gene had lower blood glucose levels and lower body weight. It also revealed that this gene was involved in muscle function and the animals had a lower grip strength.

In order to study gene function, the EUMODIC consortium produced mouse lines which each had a single gene turned off. These mouse lines were then analysed in mouse clinics, where each mouse was assessed by a series of tests and investigations, allowing the researchers to establish the functions of the missing genes.

EUMODIC was the first step towards the creation of a database of mouse gene functions, a vision now being realised by the International Mouse Phenotyping Consortium (IMPC).

The IMPC incorporates centres from across the globe with the aim of uncovering the functions of all 20,000 genes in the mouse genome. IMPC builds on the groundwork and achievements of EUMODIC in establishing the procedures and processes to identify and catalogue the functions of genes.

“EUMODIC leaves a powerful legacy that will live on in the IMPC and the data and resources it has provided for scientists. EUMODIC and IMPC will be truly transformative for medical research by revealing the roles that different genes play in disease.”

Professor Steve Brown Director of the MRC Mammalian Genetics Unit at Harwell and the coordinator of the EUMODIC consortium

This was the first time such a project has been attempted on this scale with multiple centres cooperating together from different countries. The consortium had to establish new standardised procedures to generate and assess the mouse lines and a central European database to store all the data.

The aim of the project was to understand more about genes we currently know very little about, and open up new avenues for research into the genetics of human disease. All the findings have been made publically available, allowing other scientists to use them in their own research.

Overall the Sanger Institute has generated and extensively phenotyped over 1,000 mouse lines, making these data available to the community.

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Funding

The EUMODIC project was funded by the European Commission contract number LSHG-CT-2006-037188. The work at TCP was funded under the NorCOMM project by the Government of Canada through Genome Canada and Genome Prairie. ICS been supported by French state funds through the ‘Agence Nationale de la Recherche’ under the frame programme Investissements d’Avenir labelled ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN.