|Genomics Meets Medicine on New Gene Map|
By Kate Dalke
April 18, 2003
A new map of chromosome 7, one of the best-studied and medically important human chromosomes, has just been published. The map, created with the help of some 90 researchers around the world—including those at Celera Genomics in Rockville, Maryland—reveals the locations of genes and mutations associated with diseases such as cystic fibrosis, leukemia, obesity, and autism, among others.
What distinguishes this map from the maps of other recently published chromosomes are first, the combination of data from the public and private groups, and second, the extent to which the map incorporates information about patients.
Chromosome 7 is the largest human chromosome to be sequenced and “finished,” which means that it is highly accurate and complete. The map is significant because the researchers sought to transform the sequence from raw information into a tool that, as it is further refined, can be used by physicians.
“The chromosome sequence is just a means to an end,” says Stephen W. Scherer, of the University of Toronto, who led the research. “We wanted to get the sequence in a form that was most usable by the medical genetics community.”
The map, reported in Science, is part of a larger project to represent chromosome abnormalities, genes, and mutations associated with specific diseases in an accessible way. A database and Web site have been established to continually improve the map as new data are incorporated.
In four days following the map’s publication, the Canadian group had nearly 14,000 hits to their Chromosome 7 Genome Browser.
The project’s creators say that the map will be considered a success when “an equal number of molecular biologists, medical geneticists, and physicians use the information.”
“This is really the first paper to integrate patient data and medically relevant data into the story of the chromosome structure,” says Richard J. Mural of Celera. “And this is how we envisioned the sequence being used.”
The map shows the locations of 440 disease-related chromosomal rearrangements—locations where the DNA has shifted.
For example, the map includes chromosomal rearrangements from three autism patients. One patient’s rearrangement mapped near the FOXP2 gene, which has been linked to a speech and language disorder. Another patient’s rearrangement overlapped with a "breakpoint" associated with a speech and language disorder. And the third patient’s was near a gene involved in neuron synapses.
The scientists are now investigating whether mutations in these genes and regions are found in autism families.
The Canadian government funded the new map of chromosome 7. Analysis of genome sequence, chromosome by chromosome, was largely set aside in the United States in the mid-1990s as efforts and funding went towards whole-genome sequencing.
“Fortunately for us, however, we were able to convince our Canadian funding agencies about the value of continuing this work,” says Scherer.
Among their findings, Scherer and his many colleagues discovered a high percentage of long stretches of DNA present in more than one copy that have been associated with diseases such as Williams-Beuren syndrome and Shwachman-Diamand syndrome.
Only smaller chromosomes, such as 20, 21 and 22, have been comparably sequenced and analyzed. Chromosome 7 makes up five percent of the human genome.
The Human Genome Project will publish its version of a finished sequence of chromosome 7 later this year. As an author of the forthcoming and competing paper, Eric D. Green, of the US National Human Genome Research Institute in Bethesda, Maryland, said he could not comment on the present study.
However, David Schlessinger of the National Institute of Aging at the National Institutes of Health in Bethesda, Maryland, says, “It’s a more refined version of chromosome 7 that is more useful to the community."
Martin Godbout, President and CEO of Genome Canada said, “It exemplifies how genetic, genomic, and clinician scientists in the public and private sectors worldwide can work together in a common goal to understand the human genome and its role in health and disease.”
Diseases and abnormalities on chromosome 7
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