Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations

Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) in both humans and dogs. Studies implicating the phenotypic consequences of SNX14 mutations to be consequences of subcellular disruption to autophagy and lipid metabolism have been limited to in vitro investigation of patient-derived dermal fibroblasts, laboratory engineered cell lines and developmental analysis of zebrafish morphants. SNX14 homologues Snz (Drosophila) and Mdm1 (yeast) have also been conducted, demonstrated an important biochemical role during lipid biogenesis. In this study we report the effect of loss of SNX14 in mice, which resulted in embryonic lethality around mid-gestation due to placental pathology that involves severe disruption to syncytiotrophoblast cell differentiation. In contrast to other vertebrates, zebrafish carrying a homozygous, maternal zygotic snx14 genetic loss-of-function mutation were both viable and anatomically normal. Whilst no obvious behavioural effects were observed, elevated levels of neutral lipids and phospholipids resemble previously reported effects on lipid homeostasis in other species. The biochemical role of SNX14 therefore appears largely conserved through evolution while the consequences of loss of function varies between species. Mouse and zebrafish models therefore provide valuable insights into the functional importance of SNX14 with distinct opportunities for investigating its cellular and metabolic function in vivo

Commercially Available Outbred Mice for Genome-Wide Association Studies

Genome-wide association studies using commercially available outbred mice can detect genes involved in phenotypes of biomedical interest. Useful populations need high-frequency alleles to ensure high power to detect quantitative trait loci (QTLs), low linkage disequilibrium between markers to obtain accurate mapping resolution, and an absence of population structure to prevent false positive associations. We surveyed 66 colonies for inbreeding, genetic diversity, and linkage disequilibrium, and we demonstrate that some have haplotype blocks of less than 100 Kb, enabling gene-level mapping resolution. The same alleles contribute to variation in different colonies, so that when mapping progress stalls in one, another can be used in its stead. Colonies are genetically diverse: 45% of the total genetic variation is attributable to differences between colonies. However, quantitative differences in allele frequencies, rather than the existence of private alleles, are responsible for these population differences. The colonies derive from a limited pool of ancestral haplotypes resembling those found in inbred strains: over 95% of sequence variants segregating in outbred populations are found in inbred strains. Consequently it is possible to impute the sequence of any mouse from a dense SNP map combined with inbred strain sequence data, which opens up the possibility of cataloguing and testing all variants for association, a situation that has so far eluded studies in completely outbred populations. We demonstrate the colonies' potential by identifying a deletion in the promoter of H2-Ea as the molecular change that strongly contributes to setting the ratio of CD4+ and CD8+ lymphocytes

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

Mouse genomic variation and its effect on phenotypes and gene regulation

We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism

Testing Satisfaction with a Group-based Social Work Field Liaison Model: A Controlled Mixed Methods Study

Social work field education programs rely on the liaison process to oversee and support students during their placement and to assist them to integrate theory and practice. However, the role and importance of liaison has been threatened as social work programs seek alternative and cost-effective ways to undertake these functions. This paper presents findings from a pilot study investigating levels of satisfaction among students and field educators with an innovative group liaison model compared to a control group who experienced the standard liaison practice. Fifty-three students and 47 field educators completed the survey. Twenty-one of the students and 10 of the educators received the intervention (the group liaison); the remaining 32 students and 37 educators received the standard liaison process (the control group). Students in the intervention group reported significantly higher levels of satisfaction with all aspects of the liaison experience than students who received the standard liaison process. Field educators were more positive about liaison than students. This study reaffirms the contribution of face-to-face liaison contact to the student learning experience on placement and suggests that strengthening, rather than devaluing, the liaison role could be a useful strategy to encourage the field’s ongoing commitment to provision of quality placement-based learning opportunities

Mapping social work field education in the 21st century: a national survey of the Australian context

Field education is a key curriculum component in social work programmes and students identify their placement as central to their transition to practice. Globally, changes in higher education, increasing complexity of practice and an increasingly diverse student body, are challenging field education programmes to meet these professional and resource challenges. This paper reports on Australian research which surveyed social work field education programmes in relation to staffing, supervision and other developments shaping social work field education. Twenty-four field education coordinators of 30 social work programmes completed the survey and the findings highlighted worrying trends including increasing student to staff ratio, insufficient social worker supervised placements, increased placements with external [off-site] supervision and employment of causal staff to undertake core tasks such as supervision and liaison. The results provide important benchmarking evidence which will resonate with the wider international social work education context

Innovative field options

"A practical guide for educators and managers involved in supervising field education. Drawing on the experience of academics, clinicians and educators from Australia, New Zealand, Canada and the UK, the collection explores how to make the most of fieldwork experience."--Libraries Australi

Exploring the Potential of a Collaborative Web-based E-portfolio in Social Work Field Education

In most Australian workplaces that provide placement opportunities, social workers are unlikely to receive reductions in their workload for supervising students and completing the administrative requirements of field education subjects. Associated time costs lead to reluctance to supervise social work students. This article investigates the potential for a web-based e-portfolio tool to support and streamline social work field education and assessment processes. Social work students, field educators, and university-appointed liaison staff (N = 110) from a large Australian university completed an online survey administered at the end of placement. The majority of participants reported that the e-portfolio provided a useful framework for recording evidence of student learning; was simple to use; saved time; and had the capacity to enhance the quality and immediacy of communication between parties. We argue that e-portfolios can efficiently capture evidence of student learning and provide a robust mode of supporting social work students on placement

Creating a standardised teaching and learning framework for social work field placements

Mapping and evaluating a student's progress on placement is a core element of social work education but there has been scant attention to indicate how to effectively create and assess student learning and performance. This paper outlines a project undertaken by the Combined Schools of Social Work to develop a common learning and assessment tool that is being used by all social work schools in Victoria. The paper describes how the Common Assessment Tool (CAT) was developed, drawing on the Australian Association of Social Work Practice Standards, leading to seven key learning areas that form the basis of the assessment of a student's readiness for practice. An evaluation of the usefulness of the CAT was completed by field educators, liaison staff, and students, which confirmed that the CAT was a useful framework for evaluating students' learning goals. The feedback also identified a number of problematic features that were addressed in a revised CAT and rating scale