Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
An international consortium has constructed a map of the mouse (Mus musculus) genome. It provides a framework on which genomicists now will assemble the whole-genome shotgun sequence data. "A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA, "the team explains in Nature, dated July 31, 2002. Their paper is titled: "A physical map of the mouse genome."
The co-authors comprise the usual genome-sequencing suspects - Sangar Institute in Cambridge, U.K.; Genome Sequencing Center at Washington University in St. Louis; British Columbia Cancer Center in Vancouver; The Institute for Genome Research in Rockville, Md. - et al.
Large blocks of correspondence between the mouse and human genome chromosomal sequences enabled the researchers to correctly place how the chunks of mouse sequence that have been decoded might be laid out. "The human sequence," they write, "may be used to facilitate construction of other mammalian genome maps using the same strategy." As an added bonus, the mouse map may now serve as a reference to close gaps in the map of the human genome.
"When it is complete, the sequence of the mouse genome will have a huge impact on biological research and human health," the authors foresee. "It will provide critical information and reagents for use in mouse experimental models, making it possible to unravel the mechanisms of complex mammalian biological processes and human disease. The mouse genome sequence will provide the first opportunity to compare the complete sequence and organization of the human genome with that of another mammalian species."
The map contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches. Completion of the entire sequence is scheduled for 2005. "It will also be possible," the Nature paper concludes, "to identify the evolutionary events at the sequence level that have occurred since divergence of the two species."
Unexpected Epilepsy Occurring In Laboratory Rats Points To Mechanism Of Possible Human Relevance
Interested in how and why nerve cells die in neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), neuroscientists at Johns Hopkins University in Baltimore found themselves with a new rat model of epilepsy. This disorder in man and beast is marked not by death but by rapid and uncontrolled firing of brain cells.
The authors' unexpected animal finding is reported in the current Journal of Neuroscience, dated Aug. 1, 2002. Their article is titled: "A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy."
Aware that excess amounts of glutamate, a neuronal messenger, can kill brain cells by overstimulating them, the co-authors thought that preventing it from getting into cells might lead to apoptosis. But blocking one of glutamate's main transporters did no such thing. Instead of apoptotic nerve cells, the rats developed epilepsy. In this animal mode it takes the behavioral form of fixed staring and bodily freezing, with occasional forepaw spasms.
"We wanted to see how reducing transport of this messenger affected other brain chemicals and the brain itself," recounted the paper's senior author, Jeffrey Rothstein. He added, "Now we have to track it down in people to see if the same mechanism is involved in the human condition."
Epilepsy has long been tied to reduced levels of the neurotransmitter GABA (gamma-aminobutyric acid), which damps down a cell's likelihood of firing - as in an epileptic seizure. However the stimulating messenger glutamate had never been linked to epilepsy in people or animals.
The authors discovered that the glutamate transporter they inhibited imports glutamate molecules used by cells to make new GABA. The rats couldn't do that, so during the course of 10 days, their GABA levels dropped and epileptic seizures occurred. "Previously," Rothstein observed, "only glutamate made inside the cell - rather than being imported - was thought to contribute to GABA manufacture. While glutamate transport problems may not contribute to human epilepsy," he concluded, "our finding may provide novel therapeutic modalities for the treatment of epilepsy."
Quixotic Nasopharyngeal Sarcoma Reveals Its Chromosomal Secrets To Chinese Geneticists
Nasopharyngeal carcinoma (NPC) has a puzzling epidemiology. It accounts for 18 percent to 25 percent of the NPC cancers diagnosed in southern China, Hong Kong, Singapore, Kenya, Tunisia and Sudan - but only 0.2 percent in the U.S. Emigrants from high-prevalence areas to low-prevalence areas continue to carry a high risk of contracting NPC, but in first- and second-generation descendants these risks decline progressively. Environmental factors are thought to include Epstein-Barr infection, smoky surroundings and eating salted fish and smoked meat.
Partly because of the large environmental component, geneticists have had a hard time getting a handle on NPC. A perseverant group of scientists at Sun-Yat-sen University in the Guangzhou Province of mainland China now report the first chromosomal locus linked with this type of malignancy. Their report appears in Nature Genetics, released online July 15, 2002. The paper's title: "Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4."
The co-authors scanned the genomes of 32 Cantonese-speaking Guangzhou families and found a small region on chromosome 4 significantly associated with NPC. They discovered an even stronger linkage when they factored in the presence of antibodies to Epstein-Barr virus - evidence of prior infection - providing a useful lead to gene hunters.