Clearing a path through the patent thicket

Patents do not always promote innovation, particularly when they restrict access to fundamental scientific discoveries and the tools of basic research. However, there are legal and policy approaches that may help to ameliorate problems associated with patenting these sorts of inventions.     

Clearing the path for germ cells

The chemokine SDF-1a and its receptor CXCR4b guide germ cell migration in zebrafish by activating downstream signaling events. Boldajipour et al. (2008) now report that a second SDF-1a receptor, CXCR7, is also required for guided migration but does not function as a signaling receptor, and instead sequesters SDF-1a. These results highlight the importance of ligand clearance during guided cell migration.     

Chicken genomics charts a path to the genome sequence.

In this paper, the current status of chicken genomics is reviewed. This is timely given the current intense activity centred on sequencing the complete genome of this model species. The genome project is based on a decade of map building by genetic linkage and cytogenetic methods, which are now being replaced by high-resolution radiation hybrid and bacterial artificial chromosome (BAC) contig maps. Markers for map building have generally depended on labour-intensive screening procedures, but in recent years this has changed with the availability of almost 500,000 chicken expressed sequence tags (ESTs). These resources and tools will be critical in the coming months when the chicken genome sequence is being assembled (eg cross-checked with other maps) and annotated (eg gene structures based on ESTs). The future for chicken genome and biological research is an exciting one, through the integration of these resources. For example, through the proposed chicken Ensembl database, it will be possible to solve challenging scientific questions by exploiting the power of a chicken model. One area of interest is the study of developmental mechanisms and the discovery of regulatory networks throughout the genome. Another is the study of the molecular nature of quantitative genetic variation. No other animal species have been phenotyped and selected so intensively as agricultural animals and thus there is much to be learned in basic and medical biology from this research.     

The shock of the new: progress in schizophrenia genomics

A growing list of common and rare genetic risk variants are being implicated in schizophrenia susceptibility. As with other complex genetic disorders most of the variance in genetic risk is still to be attributed. What can be learned from progress to date? The available data challenges how we conceptualize schizophrenia and suggests strong aetiological links with other psychiatric and developmental disorders. With the identification of rare copy number risk variants implicating specific genes (e.g. VIPR2 and NRXN1) it is increasingly possible to investigate molecular aetiology in patient subgroups to establish whether schizophrenia represents one or many different disease processes. This review summarizes recent research progress and suggests how the tools of modern genomics and neuroscience can be applied to best understand this devastating disorder.     

Refractions through culture: the new genomics in Iceland

This paper explores the processes whereby complex scientific developments are rendered into locally intelligible idioms as part of strategies to incorporate a ‘public’ in decisions which may have profound implications in the longer term. We focus in particular on the recent developments in genetic technologies and take as our example the deCode biogenetic project in Iceland. We trace how the images and metaphors drawn upon by all sides of the debate created powerful resonances with Icelandic history and culture. We analyse these representations and the broader themes of ethnicity and nationalism which they invoke.     

Legume comparative genomics: progress in phylogenetics and phylogenomics

The legumes are the focus of numerous rapidly expanding genomic projects, all of which involve members of one part of the Leguminosae, the subfamily Papilionoideae. This subfamily is monophyletic, and recent studies concur on a series of clades within it that are well supported and have received informal names. These include the Cladrastis clade, the genistoids (including Lupinus), the mirbelioids, the dalbergioids (including Arachis), the millettioids (including Glycine and Phaseolus), and the hologalegina (galegoid) legumes, which comprise the robinioids (including Lotus) and the inverted repeat loss (IRL) clade (including Medicago and Pisum). The canavanine-accumulating legumes appear to fall into a single clade, consistent with the idea that the production of this toxic amino acid evolved only once. Recent advances in analytical techniques for dating phylogenies support an 'early explosion hypothesis', suggesting that much of the morphological diversity of the legume family evolved rapidly around 50-60 million years ago. Within the papilionoids, the divergence between Glycine and Medicago is estimated to have taken place around 54 million years ago. There is strong evidence for a palaeoduplication event that affected both Glycine (a millettioid) and Medicago (from the IRL clade). As more genomic data are forthcoming for Arachis, it will be possible to test whether this event extends to the dalbergioids.     

Heart failure: advances through genomics

Heart failure is an increasingly prevalent and highly lethal disease that is most often caused by underlying pathologies, such as myocardial infarction or hypertension, but it can also be the result of a single gene mutation. Comprehensive genetic and genomic approaches are starting to disentangle the diverse molecular underpinnings of both forms of the disease and promise to yield much-needed novel diagnostic and therapeutic options for specific subtypes of heart failure.     

From a sow's ear to a silk purse: real progress in porcine genomics

An incredible amount of progress has occurred in the past decade since the pig genome map began to develop. The porcine genetic linkage map now has nearly 5,000 loci including several hundred genes, microsatellites and amplified fragment length polymorphism (AFLP) markers being added to the map. Thanks to somatic cell hybrid panels and then radiation hybrid panels the physical genetic map is also growing rapidly and now has over 4,000 genes and markers. Many quantitative trait loci (QTL) scans have been completed and together with candidate gene analyses have identified important chromosomal regions and individual genes associated with traits of economic interests. Using marker assisted selection (MAS) the commercial pig industry is actively using this information and traditional performance information to improve pig production. Large scale pig arrays are just now beginning to be used and co-expression of thousands of genes is now advancing our understanding of gene function. The pig's role in xenotransplantation and biomedical research makes the study of its genome important for the study of human disease. Sequencing of the pig genome appears on the near horizon. This commentary will discuss recent advances in pig genomics, directions for future research and the implications to both the pig industry and human health.     

Foreword. A path towards agricultural productivity: cereal genomics

Plant Molecular Biology -     

Brassica genomics: a complement to, and early beneficiary of, the Arabidopsis sequence

Those studying the genus Brassica will be among the early beneficiaries of the now-completed Arabidopsis sequence. The remarkable morphological diversity of Brassica species and their relatives offers valuable opportunities to advance our knowledge of plant growth and development, and our understanding of rapid phenotypic evolution.     

Functional genomics in Arabidopsis: large-scale insertional mutagenesis complements the genome sequencing project

The ultimate goal of genome research on the model flowering plant Arabidopsis thaliana is the identification of all of the genes and understanding their functions. A major step towards this goal, the genome sequencing project, is nearing completion; however, functional studies of newly discovered genes have not yet kept up to this pace. Recent progress in large-scale insertional mutagenesis opens new possibilities for functional genomics in Arabidopsis. The number of T-DNA and transposon insertion lines from different laboratories will soon represent insertions into most Arabidopsis genes. Vast resources of gene knockouts are becoming available that can be subjected to different types of reverse genetics screens to deduce the functions of the sequenced genes.     

Progress in Arabidopsis genome sequencing and functional genomics

Arabidopsis thaliana has a relatively small genome of approximately 130 Mb containing about 10% repetitive DNA. Genome sequencing studies reveal a gene-rich genome, predicted to contain approximately 25000 genes spaced on average every 4.5 kb. Between 10 to 20% of the predicted genes occur as clusters of related genes, indicating that local sequence duplication and subsequent divergence generates a significant proportion of gene families. In addition to gene families, repetitive sequences comprise individual and small clusters of two to three retroelements and other classes of smaller repeats. The clustering of highly repetitive elements is a striking feature of the A. thaliana genome emerging from sequence and other analyses.     

Genotype first: Clinical genomics research through a reverse phenotyping approach

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Multiple independent defective suppressor-mutator transposon insertions in Arabidopsis: a tool for functional genomics.

A new system for insertional mutagenesis based on the maize Enhancer/Suppressor-mutator (En/Spm) element was introduced into Arabidopsis. A single T-DNA construct carried a nonautonomous defective Spm (dSpm) element with a phosphinothricin herbicide resistance (BAR) gene, a transposase expression cassette, and a counterselectable gene. This construct was used to select for stable dSpm transpositions. Treatments for both positive (BAR) and negative selection markers were applicable to soil-grown plants, allowing the recovery of new transpositions on a large scale. To date, a total of 48,000 lines in pools of 50 have been recovered, of which approximately 80% result from independent insertion events. DNA extracted from these pools was used in reverse genetic screens, either by polymerase chain reaction (PCR) using primers from the transposon and the targeted gene or by the display of insertions whereby inverse PCR products of insertions from the DNA pools are spotted on a membrane that is then hybridized with the probe of interest. By sequencing PCR-amplified fragments adjacent to insertion sites, we established a sequenced insertion-site database of 1200 sequences. This database permitted a comparison of the chromosomal distribution of transpositions from various T-DNA locations.     

Comparative genomics of Arabidopsis and maize: prospects and limitations

The completed Arabidopsis genome seems to be of limited value as a model for maize genomics. In addition to the expansion of repetitive sequences in maize and the lack of genomic micro-colinearity, maize-specific or highly-diverged proteins contribute to a predicted maize proteome of about 50,000 proteins, twice the size of that of Arabidopsis.