Globally, wheat is the most widely grown crop and one of the three most important crops for human and livestock feed. However, the complex nature of the wheat genome has, until recently, resulted in a lack of single nucleotide polymorphism (SNP)-based molecular markers of practical use to wheat breeders. Recently, large numbers of SNP-based wheat markers have been made available via the use of next-generation sequencing combined with a variety of genotyping platforms. However, many of these markers and platforms have difficulty distinguishing between heterozygote and homozygote individuals and are therefore of limited use to wheat breeders carrying out commercial-scale breeding programmes. To identify exome-based co-dominant SNP-based assays, which are capable of distinguishing between heterozygotes and homozygotes, we have used targeted re-sequencing of the wheat exome to generate large amounts of genomic sequences from eight varieties. Using a bioinformatics approach, these sequences have been used to identify 95266 putative single nucleotide polymorphisms, of which 10251 were classified as being putatively co-dominant. Validation of a subset of these putative co-dominant markers confirmed that 96% were true polymorphisms and 65% were co-dominant SNP assays. The new co-dominant markers described here are capable of genotypic classification of a segregating locus in polyploid wheat and can be used on a variety of genotyping platforms; as such, they represent a powerful tool for wheat breeders. These markers and related information have been made publically available on an interactive web-based database to facilitate their use on genotyping programmes worldwide.

Food security is a global concern and substantial yield increases in cereal crops are required to feed the growing world population. Wheat is one of the three most important crops for human and livestock feed. However, the complexity of the genome coupled with a decline in genetic diversity within modern elite cultivars has hindered the application of marker-assisted selection (MAS) in breeding programmes. A crucial step in the successful application of MAS in breeding programmes is the development of cheap and easy to use molecular markers, such as single-nucleotide polymorphisms. To mine selected elite wheat germplasm for intervarietal single-nucleotide polymorphisms, we have used expressed sequence tags derived from public sequencing programmes and next-generation sequencing of normalized wheat complementary DNA libraries, in combination with a novel sequence alignment and assembly approach. Here, we describe the development and validation of a panel of 1114 single-nucleotide polymorphisms in hexaploid bread wheat using competitive allele-specific polymerase chain reaction genotyping technology. We report the genotyping results of these markers on 23 wheat varieties, selected to represent a broad cross-section of wheat germplasm including a number of elite UK varieties. Finally, we show that, using relatively simple technology, it is possible to rapidly generate a linkage map containing several hundred single-nucleotide polymorphism markers in the doubled haploid mapping population of Avalon × Cadenza.

The waterfall life cycle model suffers from a number of problems but in spite of this, it continues to be the most widely used life cycle model. A different life cycle approach is proposed that emphasizes the product life cycle rather than the project life cycle, quality management priorities rather than project management priorities and views of quality rather than views of the project schedule. A quality management tool based on different views of quality is used to identify the "gaps" that inevitably exist between a user's needs, the requirements specification and the product that is delivered. This is followed by a brief discussion of how these "gaps" can be closed.

We have developed a genotyping system for detecting genetic contamination in the laboratory mouse based on assaying single-nucleotide polymorphism (SNP) markers positioned on all autosomes and the X chromosome. This system provides a fast, reliable, and cost-effective way for genetic monitoring, while maintaining a very high degree of confidence. We describe the allelic distribution of 235 SNPs in 48 mouse strains, thereby creating a database of polymorphisms useful for genotyping purposes. The SNP markers used in this study were chosen from publicly available SNP databases. Four genotyping methods were evaluated, and dynamic two-tube allele-specific PCR assays were developed for each marker and tested on a set of 48 inbred mouse strains. The minimal number of assays sufficient to distinguish groups consisting of different numbers of mouse strains was estimated, and a panel of 28 SNPs sufficient to distinguish virtually all of the inbred strains tested was selected. Amplifluor SNP detection assays were developed for these markers and tested on an extended list of 96 strains. This panel was used as a genetic quality control approach to monitor the genotypes of nearly 300 inbred, wild-derived, congenic, consomic, and recombinant inbred strains maintained at The Jackson Laboratory. We have concluded that this marker panel is sufficient for genetic contamination monitoring in colonies containing a large number of genetically diverse mouse strains and that reduced versions of the panel could be implemented in facilities housing a lower number of strains.

A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average approximately 1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608+/-136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies.

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

This paper introduces The Layered Systems Model and describes how it can be applied to assist project managers to be effective at all stages of project design and delivery. Conventional rational problem solving techniques for difficult projects are supplemented with imaginative and relationship‐focused approaches. The Layered Systems Model is a management tool for focusing on different levels of functioning in projects, organisations, and teams. The model acts like a series of “filters to perception” to assist managers to assess how well an organisation is functioning at each level. It can be applied to large organisations, departments, and small work groups or in the case of this paper, software project teams. The paper shows how the Layered Systems Model can happily coexist with the Project Management Institute’s eight project knowledge areas to form a powerful diagnostic tool for software projects which are not quite “out of control” but are heading in that direction.

It has been suggested that ageing, or at least some of its symptoms, are related to a physiological decline in growth hormone (GH) levels with age.To elucidate the molecular mechanisms behind GH-dependent changes in aged animals, we have analysed GH-mediated effects on gene expression in old male rats through the application of cDNA representational difference analysis in combination with RNase protection assays and DNA macroarrays on nylon filters.In addition to well-characterized GH-regulated genes, we demonstrate the differential expression of at least 11 genes not previously known to be under GH control.Several transcripts encoding enzymes and receptors involved in the metabolism of protein, carbohydrates and lipids were identified.Another group of transcripts consisted of gene products encoding proteins involved in the immune system.This list of expressed genes in GH-treated old rats may shed further insight on the action and mechanism behind the positive effects of GH on, for example, body composition and immune responses observed in different animal and human studies.

The introduction of quasi-markets into the public sector suggests that entrepreneurship may have an increasing role to play within the resulting new structures. This article examines the nature of public sector entrepreneurship in the context of the new arrangements for the provision of primary care in the UK. Preliminary evidence points to the existence of different types of entrepreneurship. In particular, there is evidence of entrepreneurship in the form of the reduction in inefficiency, price-quality arbitrage and innovation. There is also evidence to suggest that the GPs became fundholders early on are rather more entrepreneurial than those who have adopted fundholding at a later stage.

Over the last decade there have been significant changes to the traditional purchaser-supplier relationship within industrial organizations. This has involved reforming old-style purchasing relationships, which relied on several alternative suppliers competing mainly on price, to the preferred single-sourcing relationships, with accompanying mutuality of benefits to the partners involved. This change has been highlighted by the success of Japanese manufacturing firms. However, the process of change is a difficult task for any organization to achieve. It is even more difficult in public-sector organizations, where profit-maximizing aims have not been central to organizational behaviour, and where past practice has been the basis for current operational decisions. However, government policy of privatization and the development of public sector ‘quasi-markets’ has resulted in a shift of emphasis and a consequent re-examination of operational practices in the light of market discipline. Public-sector organizations operate in markets constrained by political parameters, but privatization and the development of a commercial approach have led to many public-sector organizations' adopting the business style of private sector companies. This paper aims to recount some of the problems that British Rail (BR) experienced in this transition period and how it managed this change process, and to summarize some of the key considerations for developing and sustaining ‘partnerships’ between purchaser and supplier.

Aims to assist in improving managerial effectiveness by presenting a view of six different levels of functioning in organizations, together with a means of assessing how well an organization is functioning at each level. This assessment should enable managerial energy to be clearly focused on the most important aspects of an organization’s functioning. The model presented ‐ the “layered systems model” ‐ is intended to support and reinforce models and theories already subscribed to, and to provide an improved means of transforming managerial theory into practice. The model helps make sense of the complexity, ambiguity and contradictions involved in managing the everyday workings of an organization and in managing the processes of organizational change.

Examines how and why some major UK purchaser and supplier organizations have increasingly sought to become partners. Drawing on detailed case studies of Rank Xerox, Hoover, ICL and British Rail discusses the dynamics of partnership sourcing, and analyses and exemplifies the costs and benefits to both partners and suppliers. Suggests that both partners benefit from the increased commitment and improved communications that partnership brings. Argues that purchasers derive extra advantages from partnership relations in the form of the potential for a reduced supplier base and increased scope for quality improvements in supplier goods and services. Finally, considers a number of problems, opportunities and constraints on partnership sourcing. Concludes that it is the UK cultural heritage of adversarialism in purchaser‐supplier relations which present the most significant difficulties in making partnership sourcing work.