Steven G. Gray

Homology recognition: a FUGUE in a major key

‘Fugue, noun: a piece of music consisting of three or more tunes played together.’ – Cambridge International Dictionary of English. Like the definition, the concept behind FUGUE, a new sequence-structure homology recognition program, relies on three key features: improved environment-specific substitution tables from the homologous-structure alignment database (HOMSTRAD; http://www-cryst.bioc.cam.ac.uk/∼homstrad/), automatic selection of appropriate alignment algorithms, and combined information from both multiple sequences and multiple structures. Kenji Mizuguchi and colleagues at Cambridge University, who developed the program, found that this method recognized 8% more homologs at the 95% specificity level than a similar equivalent PSI-BLAST, and ranked 20% more homologs at the top. Alignment accuracy was also improved. FUGUE is available at http://www-cryst.bioc.cam.ac.uk/fugue/.

The Canadian biotech initiative

With the current controversy over food production and the influence of biotechnology on our lives, a positive input is welcome. BIOTECanada represents the biotechnology sector in Canada and is dedicated to promoting a better understanding of the benefits of biotechnology. Its website (http://www.biotech.ca/) discusses how biotechnology affects our food, health and environment, including lists of pharmaceutical products and GM foods approved for use in Canada. Safety issues are also covered, and all sections of the site have useful links to national and international agencies for further information. SG

Irish cancer statistics

There are startling differences in cancer statistics for the Irish population compared with the European Union. Irish women are much more likely to develop cancer of the esophagus than women in Europe (6.1 per 100 000 versus 2.2 per 100 000). Overall Irish people living in urban areas are 10–15% more likely to get cancer than those living in rural areas and Irish people have a 1-in-3 chance of developing cancer by age 74. These results were published in a report following the consolidation of the cancer registries of Ireland and Northern Ireland by the Ireland–Northern Ireland National Cancer Institute Cancer Consortium (http://www.allirelandnci.org). The consortium is working with the US National Cancer Institute to discover the basis for these differences. SG

HACking away at disease

The potential of human artificial chromosomes (HACs) in providing human gene therapy has now been demonstrated. These vectors can carry megabases of DNA – even entire genomic loci – and they use human functional elements, so they are increasingly seen as a safer alternative to viral-based gene therapies. But given the number of genes HACs carry, it was not certain that they would function in vivo to correct a specific genetic deficiency. Now, Zoia Larin and colleagues report the functional complementation of a genetic deficiency in cultured human cells using HACs. The authors developed a HAC containing the locus for HPRT, a gene that if mutated or lost causes a neurodevelopmental disorder. Once the HAC was transferred into HPRT-deficient cells, HPRT enzyme activity was renewed. Furthermore, the effect was stable, with the majority of cells maintaining the HPRT activity for two months. (Mejia, J.E. et al. [2001] Am. J. Hum. Genet. 69, 315–326) SG

Public gene index database

The explosion of microarray technology begs the question, where does one put all the data? An ambitious attempt to provide a comprehensive open public database to understand the expression of human genes in normal human tissues has been initiated at the Harvard Institute of Medicine. Called HuGEIndex (http://www.geneindex.org/), the database is still under construction, so search capabilities are limited. Most major organ systems are being processed, and in the coming months, gene-expression data for brain, spinal cord, liver, lung, heart, adrenal, muscle, duodenum, colon, prostate and spleen will be added. Other databases are also envisaged, including one for housekeeping genes. All expression data is measured using Affymetrix chips, and histology sections for each representative tissue are also in the database. If interested, outside parties are also encouraged to submit their own Affymetrix data to the database. SG

Picking your SNPs

Single nucleotide polymorphisms (SNPs) allow researchers to generate a wealth of data when examining genetic variation and mapping the location of disease causing genes. A novel approach to SNPs analysis has been devised by Japanese researchers, Hangil Chang and Toshiro Fujita. They have constructed a catalog of SNPs where the polymorphism changes the amino acid sequence (called nonsynonymous or nsSNPs) and is therefore more likely to change the function of the protein in question. Chang and Fujita extracted 1 190 295 SNPs from the public databases. Of these, 3793 were found to be nsSNPs and could be classified into 1247 categories based on protein function. A search of protein domains and functional sites in the SwissProt database revealed that 495 annotations contained nsSNPs, including 38 in transmembrane regions. This public database can be accessed at http://picsnp.org. (Chang, H. and Fujita, T. [2001] Biochem. Biophys. Res. Commun. 287, 288–291) SG

A new oncogenic FGF

Scientists at CuraGen have isolated a novel human fibroblast growth factor (FGF). The FGF family of proteins is involved in normal growth and development, and is implicated in several diseases, including cancer. Using a homology-based genomic-mining process, the researchers identified the cDNA for the new factor, FGF-20. FGF-20 mRNA is increased in human tumor cell lines derived from the colon, lungs, and stomach. Also, ectopic expression of this gene transforms cells in vitro and proved to be tumorigenic in mice. CuraGen is currently developing antibodies to inhibit FGF-20, in an attempt to treat human malignancies. [Jeffers, M. et al. (2001) Cancer Res. 61, 3131–3138] SG

The Janus Serum Bank: forward thinking allows retrospective analysis

Named after the two-faced Roman god, the Janus Serum Bank symbolizes the possibility of looking for the causes of disease both retrospectively and prospectively. This vital biomedical resource was highlighted in a recent JAMA publication that linked Chlamydia trachomatis serotype and cervical squamous cell carcinoma [Anttila, T. et al. (2001) JAMA 285, 47–51]. Under the control of the Norwegian Cancer Society, the bank consists of 600 000 serum samples obtained from 300 000 Norwegians during medical examinations and when donating blood. Most individuals have a time-course of sera in the bank (up to 12 samples). The Janus project currently cooperates with groups from Scandinavia, the UK, Germany, the US and Australia. Researchers can obtain between 500 to 3000 samples for projects; each sample from a patient comes with three healthy age- and sex-matched controls. The samples are coded for anonymity and the experiments are done ‘blind’ – which samples are from controls and which from patients are only revealed once the results are in. Full details about the project and how to apply for samples are given on the Norweigan Cancer Societies website (http://www.kreft.no/forhelsepersonell/janusserumbank/english/). SG.

Immunophenotyping leukemia by microarray.

Australian scientists have developed a new technique that increases the efficiency and accuracy of immunophenotyping leukemias. The technique relies on the fact different leukemias present different cluster-of-differentiation (CD) antigens on their surface. Previously, only a small number of these antigens could be used for the identification of leukemia types, because the standard technique, flow cytometry, usually only identifies three CDs per assay. To get around this limitation, Christopherson and colleagues developed a microarray incorporating 60 different CD antibodies, and used it to distinguish between normal leukocytes and various leukemias, including chronic lymphocytic leukemia (CLL). Potentially this new development could be used to diagnose leukemia, and it paves the way for the identification of new prognostic markers and antigens to measure minimal residual disease following treatment. [Belov, L. (2001) Cancer Res. 61, 4483–4489] SG

Morning-after skin repair?

A new skin care product is being developed that might help people who have been exposed to too much sun. The topical cream contains bacterial T4 DNA endonuclease, an enzyme that can recognize and repair DNA damaged by exposure to ultraviolet light. The cream was originally developed to treat individuals with xeroderma pigmentosa, a hereditary genetic disorder that disables an individuals DNA repair system, leading to extreme photosensitivity and early tumor development. Tests by Daniel Yarosh and colleagues on a cohort of affected individuals found that the cream significantly reduced the number of skin cancers. An expanded study is now envisaged for individuals without xeroderma pigmentosa who are considered to be at high risk of developing skin cancer. (Yarosh, D. et al. [2001] The Lancet 357, 926–929) SG