Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated in-bred human populations. An understanding of the population history of domestic dog breeds suggests that LD mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LD mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LD was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LD in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.

A typical migraine susceptibility region localizes to chromosome 1q31

Migraine (with and without aura) is a prevalent neurovascular disease that shows strong familial aggregation, although the number of genes involved and the mode of inheritance is not clear. Some insight into the disease has been gained from genetic studies into a rare and very severe migraine subtype known as familial hemiplegic migraine (FHM). In this study, we took a family-based linkage and association approach to investigate the FHM susceptibility region on chromosome 1q31 for involvement in typical migraine susceptibility in affected Australian pedigrees. Initial multipoint ALLEGRO analysis provided strong evidence for linkage of Chrlq31 markers to typical migraine in a large multigenerational pedigree. The 1-LOD* unit support interval for suggestive linkage spanned approximately 18 cM with a maximum allele sharing LOD* score of 3.36 obtained for marker D1S2782 (P=0.00004). Subsequent analysis of an independent sample of 82 affected pedigrees added support to the initial findings with a maximum LOD* of 1.24 (P=0.008). Utilising the independent sample of 82 pedigrees, we also performed a family-based association test. Results of this analysis indicated distortion of allele transmission at marker D1S249 [global chi2 (5) of 15.00, P=0.010] in these pedigrees. These positive linkage and association results will need further confirmation by independent researchers. However, overall they provide good evidence for the existence of a typical migraine locus near these markers on Chrlq3l, and reinforce the idea that an FHM gene in this genomic region may also contribute to susceptibility to the more common forms of migraine.

Chromosome 17 and the inducible nitric oxide synthase gene in human essential hypertension

Essential hypertension is a common multifactorial trait that results in a significantly increased risk for heart attack and stroke. The condition has a genetic basis, although at present the number of genes is unknown. In order to identify such genes, we are utilising a linkage scanning approach using microsatellite markers and affected sibships. Here we provide evidence for the location of at least one hypertension susceptibility locus on chromosome 17. Analysis of 177 affected sibpairs gave evidence for significant excess allele sharing to D17S949 (SPLINK: P=0.0029; MAPMAKER SIBS: P=0.0033; ASPEX: P=0.0061; GENEHUNTER: P=0.0096; ANALYZE (SIBPAIR): P=0.0025) on 17q22–24, with significant allele sharing also indicated for an additional marker, D17S799 (SPLINK: P=0.025; MAPMAKER SIBS: P= 0.025) located close to the centromere. Since these two genomic regions are well separated, our results indicate that there may be more than one chromosome 17 locus affecting human blood pressure. Moreover, further investigation of this chromosome, utilizing a polymorphism within the promoter of the iNOS candidate gene, NOS2A, revealed both increased allele sharing among sibpairs (SPLINK: P=0.02; ASPEX: P=0.00004) and positive association (P= 0.034) of NOS2A to essential hypertension. Hence these results indicate that chromosome 17 and, more specifically, the NOS2A gene may play a role in human essential hypertension.

A locus on the long arm of chromosome 1 as a possible cause of essential hypertension

None of the genes responsible for essential hypertension has been identified. Recent work in genetically hypertensive rats has shown linkage of blood pressure with alleles of the renin gene. Since the renin gene is a member of a conserved synteny group that in humans spans chromosome 1q21.3-32.3 and includes the gene for antithrombin III (AT3), we used linkage studies to examine the relationship between alleles of AT3 and hypertension in a family having 10 affected members. From the lod score obtained at a recombination fraction of zero the odds for linkage of AT3 and hypertension in this family were calculated as 6:1 in favour of linkage. This result provides grounds for further examination of the possible role of the 1q23 locus in the aetiology of essential hypertension.

Mapping local solutions to entrenched transport problems: Key lessons regarding the use of geographical information technologies in community mapping with disadvantaged communities

There is an increasing interest in the use of information technology as a participatory planning tool, particularly the use of geographical information technologies to support collaborative activities such as community mapping. However, despite their promise, the introduction of such technologies does not necessarily promote better participation nor improve collaboration. In part this can be attributed to a tendency for planners to focus on the technical considerations associated with these technologies at the expense of broader participation considerations. In this paper we draw on the experiences of a community mapping project with disadvantaged communities in suburban Australia to highlight the importance of selecting tools and techniques which support and enhance participatory planning. This community mapping project, designed to identify and document community-generated transport issues and solutions, had originally intended to use cadastral maps extracted from the government’s digital cadastral database as the foundation for its community mapping approach. It was quickly discovered that the local residents found the cadastral maps confusing as the maps lacked sufficient detail to orient them to their suburb (the study area). In response to these concerns and consistent with the project’s participatory framework, a conceptual base map based on resident’s views of landmarks of local importance was developed to support the community mapping process. Based on this community mapping experience we outline four key lessons learned regarding the process of community mapping and the place of geographical information technologies within this process.

More naturalness, less control: The effect of natural mapping on the co-located player experience

In the past years, there has been a surge in game controllers that allow players to play in a more physical, more natural way. In this paper we present an experimental study of the effect of gaming using these naturally mapped controllers on the player experience in a social setting. Results support the hypothesis that more naturally mapped controllers augment spatial presence. Furthermore, the results suggest that gaming with more naturally mapped controllers augment social presence for female players, but not for male players. However, gaming via naturally mapped controllers decreases perceived control and actual performance. Hence, users with high performance expectations might not benefit from gaming via naturally mapped controllers.

Mapping the conditions of penal hope

This article examines the conditions of penal hope behind suggestions that the penal expansionism of the last three decades may be at a ‘turning point’. The article proceeds by outlining David Green’s (2013b) suggested catalysts of penal reform and considers how applicable they are in the Australian context. Green’s suggested catalysts are: the cycles and saturation thesis; shifts in the dominant conception of the offender; the global financial crisis (GFC) and budgetary constraints; the drop in crime; the emergence of the prisoner re‐entry movement; apparent shifts in public opinion; the influence of evangelical Christian ideas; and the Right on Crime initiative. The article then considers a number of other possible catalysts or forces: the role of trade unions; the role of courts; the emergence of recidivism as a political issue; the influence of ‘evidence based’/‘what works’ discourse; and the emergence of justice reinvestment (JR). The article concludes with some comments about the capacity of criminology and criminologists to contribute to penal reductionism, offering an optimistic assessment for the prospects of a reflexive criminology that engages in and engenders a wider politics around criminal justice issues.

Living the indie life : mapping creative teams in a 48 hour game jam and playing with data

In contemporary game development circles the ‘game making jam’ has become an important rite of passage and baptism event, an exploration space and a central indie lifestyle affirmation and community event. Game jams have recently become a focus for design researchers interested in the creative process. In this paper we tell the story of an established local game jam and our various documentation and data collection methods. We present the beginnings of the current project, which seeks to map the creative teams and their process in the space of the challenge, and which aims to enable participants to be more than the objects of the data collection. A perceived issue is that typical documentation approaches are ‘about’ the event as opposed to ‘made by’ the participants and are thus both at odds with the spirit of the jam as a phenomenon and do not really access the rich playful potential of participant experience. In the data collection and visualisation projects described here, we focus on using collected data to re-include the participants in telling stories about their experiences of the event as a place-based experience. Our goal is to find a means to encourage production of ‘anecdata’ - data based on individual story telling that is subjective, malleable, and resists collection via formal mechanisms - and to enable mimesis, or active narrating, on the part of the participants. We present a concept design for data as game based on the logic of early medieval maps and we reflect on how we could enable participation in the data collection itself.

Risky business : mapping ethical landscapes and negotiating governance tensions when researching female offending

Whilst there is an excellent and growing body of literature around female criminality underpinned by feminist methodologies, the nitty gritty of the methodological journey is nowhere as well detailed as it is in the context of the Higher Degree Research (HDR) thesis. Thus the purpose of this paper is threefold: i) to explore a range of feminist methodologies underpinning 20 Australian HDR theses focussing on female criminality; ii) to identify and map the governance/ethics tensions experienced by these researchers whilst undertaking high risk research in the area of female offending; and iii) to document strategies drawn from negotiations, resolutions and outcomes to a range of gate-keeping issues. By exploring the strategies used by these researchers, this paper aims to: promote discussion on feminist methodologies; highlight pathways that may be created when negotiating the challenging process of accessing data pertinent to this relatively understudied area; contribute to a community of practice; and provide useful insights into what Mason & Stubbs (2010:16) refer to as “the open and honest reflexivity through the research process by describing the assumptions, and hiccups” for future researchers navigating governance landscapes.

Mirror, mirror : claiming digital places of the mundane mapping culture

This paper offers a discussion on the “mundane” or quotidian aspects of that software which might at first glance seem to be a fine example of the extraordinary. It looks at game worlds in terms of an ancient human desire to articulate place in the world and pursues a design concept which resonates with this practice in order to enable a more mundane exploitation of such spatial representations: the claiming of place.

Facile mutant identification via a single parental backcross method and application of whole genome sequencing based mapping pipelines

Forward genetic screens have identified numerous genes involved in development and metabolism, and remain a cornerstone of biological research. However, to locate a causal mutation, the practice of crossing to a polymorphic background to generate a mapping population can be problematic if the mutant phenotype is difficult to recognize in the hybrid F2 progeny, or dependent on parental specific traits. Here in a screen for leaf hyponasty mutants, we have performed a single backcross of an Ethane Methyl Sulphonate (EMS) generated hyponastic mutant to its parent. Whole genome deep sequencing of a bulked homozygous F2 population and analysis via the Next Generation EMS mutation mapping pipeline (NGM) unambiguously determined the causal mutation to be a single nucleotide polymorphisim (SNP) residing in HASTY, a previously characterized gene involved in microRNA biogenesis. We have evaluated the feasibility of this backcross approach using three additional SNP mapping pipelines; SHOREmap, the GATK pipeline, and the samtools pipeline. Although there was variance in the identification of EMS SNPs, all returned the same outcome in clearly identifying the causal mutation in HASTY. The simplicity of performing a single parental backcross and genome sequencing a small pool of segregating mutants has great promise for identifying mutations that may be difficult to map using conventional approaches.

Continuous appearance-based localisation and mapping

This thesis presents a novel approach to mobile robot navigation using visual information towards the goal of long-term autonomy. A novel concept of a continuous appearance-based trajectory is proposed in order to solve the limitations of previous robot navigation systems, and two new algorithms for mobile robots, CAT-SLAM and CAT-Graph, are presented and evaluated. These algorithms yield performance exceeding state-of-the-art methods on public benchmark datasets and large-scale real-world environments, and will help enable widespread use of mobile robots in everyday applications.

Placement Trajectory : mapping the journeys of children and young people in out-of-home care

Significant problems confront our child protection out-of-home care system including: high costs; increasing numbers of children and young people entering and remaining in care longer; high frequency of placement movement; and, negative whole-of-life outcomes for children and young people who have exited care. National policy and research agendas recognise the importance of enhancing the evidence base in out-of-home care to inform the development of policy, programs and practice, and improve longitudinal outcomes of children and young people. The authors discuss the concept of placement trajectory as a framework for research and systems analysis in the out-of-home context. While not without limitations, the concept of placement trajectory is particularly useful in understanding the factors influencing placement movement and stability. Increasing the evidence base in this area can serve to enhance improved outcomes across the lifespan for children and young people in the out-of-home care system.