Caenorhabditis elegans expressed sequence tags identify gene families and potential disease gene homologues.

A database containing mapped partial cDNA sequences from Caenorhabditis elegans will provide a ready starting point for identifying nematode homologues of important human genes and determining their functions in C. elegans. A total of 720 expressed sequence tags (ESTs) have been generated from 585 clones randomly selected from a mixed-stage C. elegans cDNA library. Comparison of these ESTs with sequence databases identified 422 new C. elegans genes, of which 317 are not similar to any sequences in the database. Twenty-six new genes have been mapped by YAC clone hybridization. Members of several gene families, including cuticle collagens, GTP-binding proteins, and RNA helicases were discovered. Many of the new genes are similar to known or potential human disease genes, including CFTR and the LDL receptor.     

The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication.

Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy.     

Isolation of a candidate gene for Norrie disease by positional cloning.

The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein.     

Telomere-associated chromosome fragmentation: applications in genome manipulation and analysis.

Telomere-associated chromosome fragmentation (TACF) is a new approach for chromosome mapping based on the non-targeted introduction of cloned telomeres into mammalian cells. TACF has been used to generate a panel of somatic cell hybrids with nested terminal deletions of the long arm of the human X chromosome, extending from Xq26 to the centromere. This panel has been characterized using a series of X chromosome loci. Recovery of the end clones by plasmid rescue produces a telomeric marker for each cell line and partial sequencing will allow the generation of sequence tagged sites (STSs). TACF provides a powerful and widely applicable method for genome analysis, a general way of manipulating mammalian chromosomes and a first step towards constructing artificial mammalian chromosomes.     

Pectinoacetals A-C: novel sterol hemiacetals from the gorgonianCtenocella pectinata

Three polyhydroxylated sterol hemiacetals, pectinoacetals A-C (1–3) have been isolated as their acetyl derivatives (4–6) from the acetic anhydride treated organic extract of the Indo-Pacific gorgonianCtenocella pectinata. These natural products were found to undergo very rapid epimerization at the C-18 chiral center and thus exist only as an equilibrium mixture of two diastereomers. The structure assignments are based on spectral studies and chemical modifications of the natural products.     

Sexual isolation betweenDrosophila melanogaster females andD. simulans males. Male mating propensities versus success in hybridization

Genetic variation has been found in males of aD. simulans population for their eagerness to hybridize withD. melanogaster females. In a search for traits involved in this hybridization, males ofD. simulans were tested for mating speed and sexual vigour. Between-male differences were detected in both sexual traits, but no relationship was noticed between them, nor with the frequency of hybridization. Thus male mating propensities appear to be unrelated to the breakdown of sexual isolation between these sibling species.     

The effect of scale changes on repetitive patterns: Influence of 6-aminonicotinamide on feather germ number

There are many examples of patterned developing systems which are size invariant: if the total size of the system is reduced, then the pattern responds by changing its scale in such a way that the number of pattern elements remains constant. This phenomenon is one of the bases which underaly the formulation of the concept of positional information, one of the great unifying ideas in developmental biology. However, there are less common examples of patterns which are size dependent. In these, alterations of overall size lead to a reduction in pattern elements. Such size-dependent patterns are therefore of theoretical interest. Here we describe how the number of feather germs along the wing bud of the developing chick embryo responds to shortening of the limb, and consider the implications of these observations.     

Extraordinary levels of cadmium and zinc in a marine sponge,Tedania charcoti Topsent: inorganic chemical defense agents

The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria.     

Membrane transport of Na and K and cell dehydration in sickle erythrocytes

The cellular concentration of Hb S plays a central role in the kinetic of Hb S polymerization and cell sickling. Blood of patients with homozygous sickle cell (SS) anemia contains a variable fraction of cells which are markedly dehydrated and have increased Hb S concentration. Since a decrease in cellular Hb S concentration reduces Hb S polymerization and sickling, the study of the processes leading to sickle cell dehydration has important pathophysiological and therapeutic implications. Sickle cell dehydration is due to cellular loss of K and Cl. K loss in sickle cells can take place via either the Ca²⁺-activated K⁺ channel, or the K?Cl cotransport, or the combined effect of oxidative damage and deformation of the red cell membrane. Inhibitors of K transport through these pathways could be used to prevent dehydration of sickle cells in vivo, provided that they can be administered safely.     

Bacterial suicide through stress

Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially, the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response also has major implications for current [food] processing methods. Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999