Over the Next 50 Years. There Is Little Doubt That Genetics Will Continue To

HIGHLIGHTS

(“The Biology of DNA”, 26 Congress of Genetics — a flagship IN BRIEF February–2 March, Cold Spring event for the community that is only Harbor Laboratory). held once every five years — also has The European scientific celebra- a genomic flavour (“Genomes — GM ORGANISMS tions will be launched with “Nobel The Linkage to Life”, 6–12 July, Day” at the World Life Sciences Melbourne, Australia). Impact of genetic manipulation on the fitness of Forum (8 April, Lyons, France), which Meetings in many other disci- Anopheles stephensi mosquitoes. boasts no fewer than 11 Nobel prize plines on which genetics has Catteruccia, F. et al. Science 299, 1225–1227 (2003) winners, including Watson,and covers had an impact on in the past 50 It has been argued that malaria could be controlled by introducing the entire breadth of the discovery’s years will be hosting symposia or into natural populations transgenic mosquitoes that express genes impact. Watson also finds time to discussions for the anniversary; that impair parasite transmission. For this strategy to be successful, attend a genome-focused symposium for example, the symposium on the transgenic mosquitoes must be able to survive and reproduce (“From Double Helix to Human “Exploiting Genomes: Bases to competitively in the wild . However, this study shows that Sequence — and Beyond” 14–15 Megabases in 50 years” at the Society transgene expression, mutations introduced by transgene April, Bethesda, USA), a Royal Society of General Microbiology’s meeting insertion, and inbreeding can result in a lower fitness of transgenic discussion meeting (“Replicating and (8–9 September, Manchester, UK). mosquitoes relative to wild type. Reshaping DNA”, 23–24 April, The Biotechnology is another area

Royal Society, London, UK) and a that owes a debt to the double helix, MOUSE MODELS conference held on the exact anniver- and later in the year a symposium at sary of the famous publication UC Berkeley (10–11 October, San Modification of ocular defects in mouse developmental (“DNA: 50 years of the Double Helix”, Francisco, USA) will explore its glaucoma models by tyrosinase. 25 April, Cambridge, UK). impact over the past 50 years Libby, R. T. et al. Science 299, 1578–1581 (2003) Following the frenzy of double- (the ubiquitous Watson will be in helix related activity in April, the pro- attendance!). Human primary congenital glaucoma (PCG) is often caused by gramme of scientific events slows So, it will be a busy year for mutations in the cytochrome P450 family member CYP1B1, and down, but continues for the rest of geneticists world-wide, but, as I’m is associated with abnormal ocular drainage structures. This the year. The annual Cold Spring sure most attendees at these meet- paper shows that Cyp1b1-deficient mice provide a good model for Harbor Symposium this year cele- ings will agree, while it must have this type of glaucoma. Libby et al. used these knockout mice to brates both the anniversary of the been great for Watson and Crick to show that tyrosinase gene deficiency increases the severity of the double helix and the impending lay the foundation stone, it is also disease phenotype and that this is alleviated by applying completion of the human genome good to be a humble bricklayer on a dihydoxyphenylalanine (L-dopa). This raises the possibility of (“The Genome of Homo sapiens”, 2 7 construction as exciting as this one. new glaucoma therapies. May–3 June). The International Nick Campbell TECHNOLOGY

RNA interference targeting Fas protects mice from FlavrSavr tomato — reached the over the next 50 years. There is fulminant hepatitis. supermarkets in 1994; and ‘Dolly little doubt that genetics will Song, E. et al. Nature Med. 19, 347–351 (2003) the sheep’ — the first cloned continue to benefit society, in mammal — was born in 1996. particular through improvements RNAi can target and silence mammalian genes but can it prevent Combining molecular biology in healthcare and agriculture. disease? Song et al. show that, in mice, RNAi can silence the gene techniques with the ever- Catherine Baxter Fas that codes for an important mediator of hepatocyte apoptosis. expanding volume of genomic, This indicates that RNAi could be used to prevent the adverse References and links proteomic and phenotypic data FURTHER READING effects of hepatitis that are linked to cell death. The authors test should enable geneticists to make The double helix – 50 years. Nature 491, this hypothesis in two models of Fas-mediated liver damage, and further exciting developments 396–453 (2003) show for the first time that siRNA can prevent disease in vivo.

Timeline | DNA milestones FUNCTIONAL GENOMICS FlavrSavr Heritable Semi-conservative First genome Successful tomato Draft human Scanning the human genome with combinatorial material found DNA replication sequenced gene commercially genome transcription factor libraries. to be DNA shown (FX174) therapy available released Blancafort, P. et al. Nature Biotech. 21, 269–274 (2003) Blancafort et al. report a new technology that could be useful for studying and modulating gene function. They have constructed 1944 1953 1958 1966 1977 1980 1983 1990 1995 1994 1996 2001 large libraries of artificial transcription factors that contain between

three and six zinc-finger domains (TFZFs) that can either activate

or repress gene expression. TFZFs can be applied to a cell line that is DNA double Genetic PCR Haemophilus ‘Dolly’ cloned Sequencing then screened for a desired phenotype. In this example, TFZFs were helix structure code methods developed influenzae described cracked published sequenced identified that were able to induce expression of the endothelial marker VE-cadherin in non-endothelial cell lines and to repress its expression when combined with a repression domain.

NATURE REVIEWS | GENETICS VOLUME 4 | APRIL 2003 | 247