Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
Williams-Beuren Syndrome (WBS) is a much-studied, highly multigenic, congenital childhood disease. Two pediatric cardiologists, J.C.P. Williams of New Zealand (1900-?) and Alois J. Beuren of Germany (1919-1984) share the syndrome's eponym. WBS is a developmental disorder caused by a microdeletion of chromosome 7's long arm.
The genomic sequence and analysis of human chromosome 7 is revealed in Nature dated July 10, 2003, under the title "The DNA sequence of human chromosome 7." Most of its precisely 100 co-authors are at the Genome Sequencing Center of Washington University in St. Louis. This is one of the three such centers that announced sequencing of the draft human genome in mid-February 2001.
Chromosome 7 is the largest of the 24 human chromosomes to have been unraveled so far. Besides WBS, number 7 has been linked to many intensively studied human diseases including cystic fibrosis, hereditary deafness and cancer. The new sequence data, which is 99.4 percent complete, show extremely good concordance with previous physical and genetic maps. Chromosome 7 is now known to contain 153 million base pairs and 1,150 protein-coding genes. Of these, 605 have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes.
The WBS region presented the single greatest challenge to the mapping and sequencing of chromosome 7. Unusually large amounts of 7's sequence are duplicated, the Nature paper reports. The repetitions may play a role in helping new genes to evolve, and may also be linked with disease. Duplicated segments were found in a region of chromosome 7 known to be associated with Williams-Beuren Syndrome. This congenital condition endows WBS children with characteristic elfin-like facial features, as well as mental retardation, growth deficiency and cardiovascular anomalies. Indeed, geneticists have an official alternative moniker for WBS: Elfin Facies Syndrome.
When Williams first defined the syndrome, he noticed that many children entering his hospital with cardiovascular problems (especially aortic stenosis) shared other traits in common. Among them, pediatricians have noted of WBS "their unusual personality, whereby the affected children are overly friendly and loquacious" - main neurological features.
Although WBS manifestations are mild, they embrace mental retardation, growth deficiency and idiopathic infantile hypercalcemia, various degrees of hypertonia (extreme tension of muscles or arteries), easy fatigability, occasional syncope (fainting due to lack of brain blood flow), bilateral corneal opacities, tooth enamel hypoplasia and cavities, and low, hoarse voices. WBS affects both sexes, with onset at birth or early infancy. In adulthood, they have prematurely aging skin and graying hair.
"The sequence we report here for chromosome 7," the Nature paper concluded, "has directly facilitated the identification of a number of genes associated with human disease. But these examples, although highly gratifying, simply represent the beginning of efforts to capitalize on the knowledge provided by finished genome sequence for better understanding the genetic bases for human health and disease."
Lancet Reports 3,000-Cohort Trial Results In Beneficial Effects Of One Drug Over Another
Results of a European study in The Lancet dated July 5, 2003, suggest that the beta-blocker agent carvedilol offers substantial survival benefit compared with another widely used beta-blocker for the treatment of chronic heart failure. The paper bears the title "Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial 9 (COMET): randomized controlled trial." Its co-authors are at the National Heart & Lung Institute at Imperial College, London.
Beta blockers reduce death in patients who are also taking diuretics and ACE inhibitors for chronic heart failure. In the COMET clinical trial, some 3,000 patients with chronic heart failure were assigned to receive twice-daily doses of carvedilol or metoprolol for about five years. Carvedilol, the paper noted, had a striking effect on reducing mortality compared with metoprolol. Average life expectancy was eight years for patients given carvedilol compared with 6.6 years for patients assigned the alternative drug. Of patients assigned carvedilol, 34 percent died during the five-year study compared with 40 percent of those assigned metoprolol.
Another study in the same issue of The Lancet highlights how carvedilol is effective in improving ventricular function for patients with heart failure due to coronary artery disease. The investigators comment how a positive response to carvedilol could obviate the need for invasive coronary revascularization in some patients with heart failure.
From Fingertips To Brain Neurons, Here's How To Sharpen Tactile Acuity Plus/Minus Drugs
German scientists improved the sense of touch in the tips of the right index fingers of human subjects without the use of drugs. Under placebo, tactile two-point discrimination was improved on the co-activated side but not on the left index finger. Then the co-authors administered drugs that either doubled or deleted these temporary gains in tactile acuity. Similar skin stimulation/drug treatment combinations may eventually help stroke victims button shirts and pianists perform more musically.
These offbeat findings occur in Science dated July 11, 2003. The paper is titled "Pharmacological modulation of perceptual learning and associated cortical reorganization." The co-authors are at the Institute for Neuroinformatics at the Ruhr-University in Bochum, Germany.
The article explained that finger stimulation and drugs can temporarily reorganize parts of the human brain. This co-activation, as it's called, shuffles the synapses that link cerebral neurons. Through changes in synapse connectivity, co-activation increases the number of neurons involved in processing tactile information.
The co-authors showed that amphetamine (a psychostimulant substance that can be abused) doubles these gains in tactile accuracy. In the presence of a second agent, a blocker of NMDA, which is an excitotoxic amino acid used to identify a subset of glutamate, the improvements in tactility gained after the finger stimulations were lost.