June 26, 2017 Credit: CC0 Public Domain

The first results from a functional genetic catalogue of the laboratory mouse has been shared with the biomedical research community, revealing new insights into a range of rare diseases and the possibility of accelerating development of new treatments and precision medicine.

The research, which generated over 20 million pieces of data, has found 360 new disease models and provides 28,406 new descriptions of the genes' effects on mouse biology and disease. The new disease models are being made available to the biomedical community to aid their research.

The International Mouse Phenotyping Consortium (IMPC) is aiming to produce a complete catalogue of mammalian gene function across all genes. Their initial results, now published in Nature Genetics, is based on an analysis of the first 3,328 genes (15 per cent of the mouse genome coding for proteins).

Lead author Dr Damian Smedley from Queen Mary University of London (QMUL) and a Monarch Initiative Principal Investigator, said: "Although next generation sequencing has revolutionised the identification of new disease genes, there is still a lack of understanding of how these genes actually cause disease.

"These 360 new disease models that we've identified in mice represent the first steps of a hugely important international project. We hope researchers will be able to use this knowledge to develop new therapies for patients, which is ultimately what we're all striving to achieve."

With its similarity to human biology and ease of genetic modification, the laboratory mouse is arguably the preferred model organism for studying human genetic disease. However, the vast majority of the mouse genome remains poorly understood, as scientists tend to focus their research on a few specific areas of the genome linked to the most common inherited diseases.

Development of therapies for rare disease lags far behind, with over half of diagnosed rare diseases still having no known causative gene. This is why the IMPC is aiming to build a complete database that systematically details the functions of all areas of the mouse genome, including neurological, metabolic, cardiovascular, respiratory and immunological systems.

Terry Meehan, IMPC Project Coordinator at European Bioinformatics Institute (EMBL-EBI) said: "Mouse models allow us to speed up patient diagnosis and develop new therapies. But before that can work, we need to understand exactly what each gene does, and what diseases it is associated with. This is a significant effort in data collection and curation that goes well beyond the capabilities of individual labs. IMPC is creating a data resource that will benefit the entire biomedical community."

The project involves going through the mouse genome systematically and knocking out a particular gene, one by one, in different mice. By looking at the mouse's resulting characteristics in a variety of standardised tests, the team then see if and how the gene knockout manifests itself as a disease, and link their findings to what is already known about the human version of the disease. The 'one by one' knockout approach lends itself to rare gene discovery, as often these diseases are caused by variants of a single gene.

More than half of the 3,328 genes characterised have never been investigated in a mouse before, and for 1,092 genes, no molecular function or biological process were previously known from direct experimental evidence. These include genes that have now been found to be involved in the formation of blood components (potentially involved in a type of anaemia), cell proliferation and stem cell maintenance.

For the first time, human disease traits were seen in mouse models for forms of Bernard-Soulier syndrome (a blood clotting disorder), Bardet-Biedl syndrome (causing vision loss, obesity and extra fingers or toes) and Gordon Holmes syndrome (a neurodegenerative disorder with delayed puberty and lack of secondary sex characteristics).

The team also identified new candidate genes for diseases with an unknown molecular mechanism, including an inherited heart disease called 'Arrhythmogenic Right Ventricular Dysplasia' that affects the heart muscle, and Charcot-Marie-Tooth disease, which is characterised by nerve damage leading to muscle weakness and an awkward way of walking.

Dr Smedley added: "In addition to a better understanding of the disease mechanism and new treatments for rare disease patients, many of the lessons we learn here will also be of value to precision medicine, where the goal is to improve treatment through the customisation of healthcare based on a patient's genomic information."

Explore further: Major mouse study reveals the role of genes in disease

More information: 'Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium' by Meehan et al., Nature Genetics. DOI: 10.1038/ng.3901

The functions of around 150 genes have been discovered by scientists across Europe in a major initiative to try to understand the part they play in disease and biology.

Roughly a third of all genes in the mammalian genome are essential for life. A new article in Nature, from an international, multi-institutional research team, including Baylor College of Medicine, describes the large-scale ...

The first known identification of two genes responsible for hypoplastic left heart syndrome (HLHS), a severe congenital heart defect, has been reported by researchers at the University of Pittsburgh School of Medicine. The ...

An international team of researchers has discovered that mutations in the human gene CWC27 result in a spectrum of clinical conditions that include retinal degeneration and problems with craniofacial and skeletal development. ...

An international team of researchers from institutions around the world, including Baylor College of Medicine, has discovered that mutations of the OTUD6B gene result in a spectrum of physical and intellectual deficits. This ...

Researchers have created a large new resource of more than 900 genes switched off one-at-a-time in mice to discover which genes are important for a wide range of biological functions such as fertility or hearing.

Whole genome sequencing involves the analysis of all three billion pairs of letters in an individual's DNA and has been hailed as a technology that will usher in a new era of predicting and preventing disease. However, the ...

The first results from a functional genetic catalogue of the laboratory mouse has been shared with the biomedical research community, revealing new insights into a range of rare diseases and the possibility of accelerating ...

Researchers have found that genes for coronary heart disease (CAD) also influence reproduction, so in order to reproduce successfully, the genes for heart disease will also be inherited.

When Ricky Ramon was 7, he went for a routine checkup. The pediatrician, who lingered over his heartbeat, sent him for a chest X-ray, which revealed a benign tumor in the top-left chamber of his heart. For Ramon, it was the ...

Gene mutations accumulating in cells are typical of the development of cancer. Finnish researchers have found that a similar accumulation of mutations occurs also in some patients with rheumatoid arthritis.

Up to 90 percent of people with amyotrophic lateral sclerosis (ALS) report that they have no family history of the disease. Now, new research has found approximately 17 percent of such ALS cases may be caused by a gene mutation, ...

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

Read the original here:

Characterizing the mouse genome reveals new gene functions and their role in human disease - Medical Xpress