Mouse Physical Map Completed

Impact on analysis of human genome information and health-care research

Vancouver, BC, Canada | A UK-US-Canada consortium - including the Genome Sciences Centre at the BC Cancer Agency - coordinated at the Wellcome Trust Sanger Institute today, publishes in Nature online the most comprehensive map of the mouse genome, containing an estimated 98 percent of the DNA sequence. The map has already proven a valuable resource in the hunt for mouse and - even more importantly - human genes.

If we are really going to maximize the utility of these data, they have to be generally available. We want biologists and health researchers everywhere to be able to think about this stuff and start imagining how this DNA sequence can be used to impact positively on the quality of life. Marco Marra Director Genome Sciences Centre

The genome of the mouse is widely regarded as one of the keys to understanding the human genome sequence. For example, comparing two sequences can highlight regions that act to control genes. Such control regions, which are very difficult to find using current methods, are crucial in understanding the role of genes in health and disease. An accurately drawn mouse genome map is vital in helping to turn human DNA sequence into a research tool for biomedicine.

"The mouse is one of the most important animal models for studying cancer and many other human diseases," explains Dr. Marco A. Marra, Director of the Genome Sciences Centre in Vancouver. "Rapid and accurate mapping of the mouse genome and linking the map to the human genome sequence will accelerate world-wide efforts to understand the molecular basis of cancer, and will provide an important genomic resource for the international research community."

The mouse map resembles an atlas of a country: it provides an overview of the genome landscape and, because all locations are indexed, it allows the user to focus rapidly on the region of interest. Any page of the mouse genome can be selected and any piece of information - or any remaining uncertainty or problem in the sequence - can be examined by concentrating the effort exclusively on the relevant place, while excluding all the other parts.

"By investing in a large-scale collaborative effort, we have been able to generate an exceptional resource that covers almost 100 percent of the mouse genome," says Simon Gregory, leader of the project at the Wellcome Trust Sanger Institute. "The map allows us to pick out the regions that are lacking in the whole genome assembly, to focus on genes and to highlight regions of similarity between mouse and human."

We've had the human genome for some time and now we have something to compare it to. This is really important for human health care and it will accelerate the pace of everything. Steven Jones Head of Bioinformatics Genome Sciences Centre

Without a map, it is not possible with current technology to sequence a large genome finished to the standards demanded by the international research community. All large genomes are finished using mapped DNA clones.

"As we move forward to interpreting the code of life, the Wellcome Trust Sanger Institute will provide a suite of resources that will accelerate discovery by biomedical researchers around the world," states Professor Allan Bradley, Director of the Wellcome Trust Sanger Institute. "The map of the mouse genome is one example of the collaborative work we do to put enabling research tools as swiftly as possible into the hands of those who need them - scientists working to understand and defeat disease."

In the two-year project, more than 300,000 randomly selected individual genomic fragments were overlapped to establish unlocalized coverage of the mouse genome - fewer than 8,000 genome segments. In a final mapping step, unique mouse chromosome data was incorporated to reduce that number still further: the published map contains fewer than 300 gaps.

"The publication of the mouse physical map represents a major milestone in our study of the function of genes in both human and mouse," says Dr. Steven Jones, Director of Bioinformatics at the Genome Sciences Centre in Vancouver. "Together with the mouse draft sequence, it is transforming the science of mouse genetics and will enormously enhance our ability to understand the role of genes in human disease."

The map will continue to be improved and developed. The value of the publication also lies in the way in which the methods developed for this project can be exploited in the future. The laboratories involved have been at the forefront of exploring technologies to provide genomic information as rapidly as possible and the mouse map is a benchmark for future work.

Very rapidly, and with little DNA sequencing, a biological repository can be produced for a species that allows researchers to home in on the regions of the genome that interest them and provides the materials to take biomedical research forward.

Dr. Marco Marra, Director, Genome Sciences Centre
photo: Nick Didlick (National Post)

In comparative genomics, new sets of information for each species are being used to improve analysis and accuracy of existing sequence sets. A major role of genomics and bioinformatics is to manage and exploit these large datasets through collaborative work and exchange.

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