Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Mental retardation is often due to fragile X syndrome. DNA analysis shows abnormal trinucleotide CGG repeats (cytosine-guanine-guanine) on the X chromosome near the end of its long arm. The incidence of fragile X syndrome (about 1 in 2,000 males) is second only to that of Down's syndrome among sources of mental retardation.

Besides the salient intellectual impairment seen in fragile X children, the syndrome features a long, narrow face with large ears, prominent jawbones, an abnormally large head and a high-arched palate. Macroorchidism - large testes - appears at puberty. Besides low I.Q. and motor incoordination, neuropsychiatric findings include hyperactivity, short attention span, poor eye contact, autistic-like behavior, jocular speech and echolalia (parrot-like echoing an interlocutor's conversation).

Now genomicists at the Wistar Institute in Philadelphia have described the discovery of a new family of gene-silencing molecular complexes in the mechanism of fragile X. Their discovery relates to a family of molecular complexes involved in repressing extensive sets of tissue-specific genes throughout the body. Additionally, one member of the family involved in repressing brain-specific genes in other tissue types include a gene thought to be responsible for X-linked mental retardation when mutated - the fragile-X syndrome.

The Wistar scientists report their research in the current issue of The Journal of Biological Chemistry, dated Feb. 28, 2003. The article is titled: "A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes." Its senior author is Ramin Shiekhattar, an associate professor at the Wistar.

"Our new findings, he observed, "may have relevance for understanding diseases characterized by uncontrolled or inappropriate gene activation and growth, with cancer perhaps the most significant of these. Other components of these complexes have been associated with leukemia.

"What really controls this?" Shiekhattar asked BioWorld Today rhetorically, and added: "For a long time, people have been looking for the factors that activate these genes, but what we and others are learning is that the critical mechanism used to regulate entire sets of genes is actually repression. In some ways," he observed, "it's like driving a car. Much of driving relies on braking rather than acceleration. Without the brake, you can't control the vehicle.

"Most of the time," Shiekhattar explained, "most of the estimated 35,000 genes in the human genome are silent - snugly stored away in the tightly coiled structure of chromatin, the raw material of chromosomes. Inside chromatin, the DNA is wound around small proteins called histones. These amino acid-rich molecules make up half of the mass of chromosomes in eukaryotic cells. Histones render DNA unavailable to the cellular machinery that would otherwise read its coded genetic information. Specific cell and tissue types are characterized," he concluded, "by the carefully controlled activation of selected sets of signature genes."

Analysis Of Affected Pedigree Members Found Mutant Gene-Causing Motor Neuron Disease

By studying a family with members suffering from an inherited form of motor neuron disease (MND) that affects the vocal cords and muscles of the face, hands and feet, scientists at the National Institute of Neurological Disorders and Stroke have identified the genetic cause of the disorder.

Their brief communication in the April 2003 issue of Nature Genetics, released online March 10, 2003, bears the title: "Mutant dynactin in motor neuron disease."

Mutation in a gene that encodes a protein involved in transporting materials within nerve cells causes muscle weakness and wasting, according to the co-authors' report. Their findings could help hone in on the causes of related ailments.

If motor neurons - nerve cells along which the brain sends instructions to muscles - become damaged, muscles start to weaken, and eventually stop working. The scientists found a mutation in a gene that codes for a component of dynactin - a protein that is part of the molecular engine that shunts materials, including nutrients, vesicles and organelles required for proper functioning and survival of nerve cells - along "tracks" within the nerve cells. The mutation reduces the ability of dynactin to bind to these microtubules, thereby disrupting axonal transport within nerve cells, and causing them, eventually, to degenerate.

Onset of MND is in early adulthood, with breathing difficulty due to vocal cord paralysis, progressive facial weakness and muscle atrophy in the hands. These symptoms in the distal lower extremities develop later. Mutation analysis in the affected family showed a single base-pair change resulting in an amino acid substitution of serine for glycine. This mutation was not found in unaffected family members or in the 200 unaffected control individuals of European descent.

Long-Abandoned Idea Of Inserting Anti-Parasite Genes Into Malarial Mosquito Vectors Revived

The idea that malaria might be controlled by introducing genes into mosquito populations to hinder or block parasite transmission was proposed more than three decades ago, but only in the past two years has it become a possibility.

New research shows that current lines of genetically modified mosquitoes do not compete well against unaltered mosquitoes in laboratory populations. The introduced genes disappeared within 16 generations. Nevertheless, transformed mosquitoes still offer hope in the battle against malaria, states a paper in Science dated Feb. 21, 2003. Its title: "Impact of genetic manipulation on the fitness of Anopheles stephensi mosquitoes." (A. stephensi is the major malaria vector in India.)

The paper's authors are at the Imperial College, London. Their findings highlight the importance of ensuring the fitness of modified mosquito populations before they are released into the wild. They evaluated various causes of the gene loss and concluded that the likeliest culprits were the foreign gene itself and severe inbreeding during engineering of the modified populations. A solution to the predicament? Simply release larger populations of transgenic insects to ensure survival of adequate numbers, the authors propose.