Prediction of multilocus identity-by-descent

Previous studies have enabled exact prediction of probabilities of identity-by-descent (IBD) in randommating populations for a few loci (up to four or so), with extension to more using approximate regression methods. Here we present a precise predictor of multiple-locus IBD using simple formulas based on exact results for two loci. In particular, the probability of non-IBD X ABC at each of ordered loci A, B, and C can be well approximated by XABC = XABXBC/XB and generalizes to X123. . .k = X12X23. . .Xk-1,k/ Xk-2, where X is the probability of non-IBD at each locus. Predictions from this chain rule are very precise with population bottlenecks and migration, but are rather poorer in the presence of mutation. From these coefficients, the probabilities of multilocus IBD and non-IBD can also be computed for genomic regions as functions of population size, time, and map distances. An approximate but simple recurrence formula is also developed, which generally is less accurate than the chain rule but is more robust with mutation. Used together with the chain rule it leads to explicit equations for non-IBD in a region. The results can be applied to detection of quantitative trait loci (QTL) by computing the probability of IBD at candidate loci in terms of identity-by-state at neighboring markers.

Identity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple Sclerosis

Genome-wide association studies (GWAS) have identified around 60 common variants associated with multiple sclerosis (MS), but these loci only explain a fraction of the heritability of MS. Some missing heritability may be caused by rare variants that have been suggested to play an important role in the aetiology of complex diseases such as MS. However current genetic and statistical methods for detecting rare variants are expensive and time consuming. 'Population-based linkage analysis' (PBLA) or so called identity-by-descent (IBD) mapping is a novel way to detect rare variants in extant GWAS datasets. We employed BEAGLE fastIBD to search for rare MS variants utilising IBD mapping in a large GWAS dataset of 3,543 cases and 5,898 controls. We identified a genome-wide significant linkage signal on chromosome 19 (LOD = 4.65; p = 1.9×10-6). Network analysis of cases and controls sharing haplotypes on chromosome 19 further strengthened the association as there are more large networks of cases sharing haplotypes than controls. This linkage region includes a cluster of zinc finger genes of unknown function. Analysis of genome wide transcriptome data suggests that genes in this zinc finger cluster may be involved in very early developmental regulation of the CNS. Our study also indicates that BEAGLE fastIBD allowed identification of rare variants in large unrelated population with moderate computational intensity. Even with the development of whole-genome sequencing, IBD mapping still may be a promising way to narrow down the region of interest for sequencing priority. © 2013 Lin et al.

Myoepithelial molecular markers in human breast carcinoma PMC42-LA cells are induced by extracellular matrix and stromal cells

The microenvironment plays a key role in the cellular differentiation of the two main cell lineages of the human breast, luminal epithelial, and myoepithelial. It is not clear, however, how the components of the microenvironment control the development of these cell lineages. To investigate how lineage development is regulated by 3-D culture and microenvironment components, we used the PMC42-LA human breast carcinoma cell line, which possesses stem cell characteristics. When cultured on a two-dimensional glass substrate, PMC42-LA cells formed a monolayer and expressed predominantly luminal epithelial markers, including cytokeratins 8, 18, and 19; E-cadherin; and sialomucin. The key myoepithelial-specific proteins α-smooth muscle actin and cytokeratin 14 were not expressed. When cultured within Engelbreth-Holm- Swarm sarcoma-derived basement membrane matrix (EHS matrix), PMC42-LA cells formed organoids in which the expression of luminal markers was reduced and the expression of other myoepithelial-specific markers (cytokeratin 17 and P-cadherin) was promoted. The presence of primary human mammary gland fibroblasts within the EHS matrix induced expression of the key myoepithelial-specific markers, α-smooth muscle actin and cytokeratin 14. Immortalized human skin fibroblasts were less effective in inducing expression of these key myoepithelial-specific markers. Confocal dual-labeling showed that individual cells expressed luminal or myoepithelial proteins, but not both. Conditioned medium from the mammary fibroblasts was equally effective in inducing myoepithelial marker expression. The results indicate that the myoepithelial lineage is promoted by the extracellular matrix, in conjunction with products secreted by breast-specific fibroblasts. Our results demonstrate a key role for the breast microenvironment in the regulation of breast lineage development.

Marker selection by Akaike information criterion and Bayesian information criterion

We carried out a discriminant analysis with identity by descent (IBD) at each marker as inputs, and the sib pair type (affected-affected versus affected-unaffected) as the output. Using simple logistic regression for this discriminant analysis, we illustrate the importance of comparing models with different number of parameters. Such model comparisons are best carried out using either the Akaike information criterion (AIC) or the Bayesian information criterion (BIC). When AIC (or BIC) stepwise variable selection was applied to the German Asthma data set, a group of markers were selected which provide the best fit to the data (assuming an additive effect). Interestingly, these 25-26 markers were not identical to those with the highest (in magnitude) single-locus lod scores.

Prediction of IBD based on population history for fine gene mapping

A novel multiple regression method (RM) is developed to predict identity-by-descent probabilities at a locus L (IBDL), among individuals without pedigree, given information on surrounding markers and population history. These IBDL probabilities are a function of the increase in linkage disequilibrium (LD) generated by drift in a homogeneous population over generations. Three parameters are sufficient to describe population history: effective population size (Ne), number of generations since foundation (T), and marker allele frequencies among founders (p). IBD L are used in a simulation study to map a quantitative trait locus (QTL) via variance component estimation. RM is compared to a coalescent method (CM) in terms of power and robustness of QTL detection. Differences between RM and CM are small but significant. For example, RM is more powerful than CM in dioecious populations, but not in monoecious populations. Moreover, RM is more robust than CM when marker phases are unknown or when there is complete LD among founders or Ne is wrong, and less robust when p is wrong. CM utilises all marker haplotype information, whereas RM utilises information contained in each individual marker and all possible marker pairs but not in higher order interactions. RM consists of a family of models encompassing four different population structures, and two ways of using marker information, which contrasts with the single model that must cater for all possible evolutionary scenarios in CM.

Literacy and identity : examining the metaphors in history and contemporary research

In this review, the authors interrogate the recent identity turn in literacy studies by asking the following: How do particular views of identity shape how researchers think about literacy and, conversely, how does the view of literacy taken by a researcher shape meanings made about identity? To address this question, the authors review various ways of conceptualizing identity by using five metaphors for identity documented in the identity literature: identity as (1) difference, (2) sense of self/subjectivity, (3) mind or consciousness, (4) narrative, and (5) position. Few literacy studies have acknowledged this range of perspectives on and views for conceptualizing identity and yet, subtle differences in identity theories have widely different implications for how one thinks about both how literacy matters to identity and how identity matters to literacy. The authors offer this review to encourage more theorizing of both literacy and identity as social practices and, most important, of how the two breathe life into each other.

The construction of social identity in newly recruited nuclear engineering staff : a longitudinal study

This study examines the process by which newly recruited nuclear engineering and technical staff came to understand, define, think, feel and behave within a distinct group that has a direct contribution to the organization's overall emphasis on a culture of reliability and system safety. In the field of organizational behavior the interactive model of social identity formation has been recently proposed to explain the process by which the internalization of shared norms and values occurs, an element critical in identity formation. Using this rich model of organizational behavior we analyzed multiple sources of data from nine new hires over a period of three years. This was done from the time they were employed to investigate the construction of social identity by new entrants entering into a complex organizational setting reflected in the context of a nuclear facility. Informed by our data analyses, we found support for the interactive model of social identity development and report the unexpected finding that a newly appointed member's age and level of experience appears to influence the manner in which they adapt, and assimilate into their surroundings. This study represents an important contribution to the safety and reliability literature as it provides a rich insight into the way newly recruited employees enact the process by which their identities are formed and hence act, particularly under conditions of duress or significant organizational disruption in complex organizational settings.

A meta-analysis of the correlation between heritage language and ethnic identity

The interaction between heritage language (HL) and ethnic identity has gained increasing scholarly attention over the past decades. Numerous quantitative studies have investigated and vindicated this interaction within certain contexts. Nevertheless, quantitative evidence on this interaction across contexts is absent to date. The current meta-analysis aims to make a contribution in this regard. By integrating relevant studies, this meta-analysis presents a powerful estimation of the reality in relation to the interaction between HL and ethnic identity. By virtue of certain retrieval strategies and selection criteria, the meta-analysis includes 43 data-sets emerging from 18 studies that have addressed the statistical correlation between the proficiency of HL and the sense of ethnic identity associated with different ethnic groups. When contrasted to one another, the results of these included studies are significantly different. However, when combined together, these studies point to a statistically significant moderate positive correlation between sense of ethnic identity and proficiency of HL across different ethnic groups. This result has a medium effect. The meta-analysis also inspires some methodological and theoretical discussions.

MILK : the Mobile Informal Learning Kit. Collaborating to design successful mobile learning applications

This paper suggests ways for educators and designers to understand and merge priorities in order to inform the development of mobile learning (m-learning) applications that maximise user experiences and hence learning opportunities. It outlines a User Experience Design (UXD) theory and development process that requires designers to conduct a thorough initial contextual inquiry into a particular domain in order to set project priorities and development guidelines. A matrix that identifies the key contextual considerations namely the social, cultural, spatial, technical and temporal constructs of any domain is presented as a vital tool for achieving successful UXD. The frame of reference provided by this matrix ensures that decisions made throughout the design process are attributable to a desired user experience. To illustrate how the proposed UXD theory and development process supports the creation of effective m-learning applications, this paper documents the development process of MILK (Mobile Informal Learning Kit). MILK is a support tool that allows teachers and students to develop event paths that consist of a series SMS question and answer messages that lead players through a series of checkpoints between point A and point B. These event paths can be designed to suit desired learning scenarios and can be used to explore a particular place or subject. They can also be designed to facilitate formal or informal learning experiences.

A grounded theory study of nursing students’ experiences in the off-campus clinical setting

Poor workplace relations are an issue of concern in many workplaces and this phenomenon is not restricted to the nursing profession. The issue of workplace violence in nursing is well documented and there are an increasing number of studies which have investigated the notion of horizontal violence amongst graduate nurses. The impact that poor workplace relations has on the development of a professional identity by nursing students in the off-campus clinical setting is significant in light of the current global shortage of nurses. There is a dearth of knowledge in understanding how Australian undergraduate nursing students experience the off-campus clinical setting and subsequently develop a professional identity as a nurse. Therefore the aim of this study was to discover and describe the phenomena in order to develop a substantive theory that explains the experiences of the undergraduate nursing students in a regional setting. Constructivist grounded theory methods were utilised in the conduct of the study. A sample of 29 participants was recruited permitting the formulation of a substantive theory regarding the development of a professional identity in nursing students. This substantive theory contributes knowledge relevant to the undergraduate nursing students, nurse educators, nursing workforce planners, and the tertiary educational institutions offering nursing. This is achieved through discovering, describing and explaining the phenomenon of ‘anxiety’ which the nursing students experience as a result of the interrelationship and interactions of tradition bearing, staff and student performance. These interactions intersect to form expectations of where the student fits within the hierarchy of the facility and the nursing profession in general. An understanding of the issues associated with tradition bearing, staff performance, and student performance and the impact that the interaction of these conditions has upon the student’s developing professional identity as a nurse is necessary to allow for the implementation of corrective strategies.

Transforming Queensland VET : Challenges and Opportunities (Volume 3)

The volume is the third in a series that addresses change and development in the delivery of VET programs in Queensland. The chapters address a breadth of issues that relate to the changing landscape for teaching and learning in VET programs through e-learning. Organisational change is a key focus of this volume. James Waterson examines business and pedagogical perspectives for SkillsTech Australia to create teaching and learning environments that will enrich the learning experience for staff and students. Kerry Emerson explores the ways in which printing teachers might change current practices in order to deliver their training to apprentices and trainees – off-the-job, onthe- job and online, through e-learning. The chapter by Erik Dodwell takes up issues of user-friendly RPL interviews and the challenges to develop a model that may be applied consistently across all industry areas using conversational interviews. The chapters by Linda Roberston, Nina Woodrow, and Anushka Weerackody discuss teaching and learning for specific groups of students. Linda Roberston proposes a vision for learning support teachers in which the learner is encouraged to be a self-directed and autonomous learner who is capable of utilising e-learning resources and is information literate. Nina Woodrow presents a case for the diminished sense of occupational identity by adult literacy teachers and the implications of this loss of expertise across the VET sector. Constructive strategies for change are outlined. The chapter by Anushka Weerackody explores ideas to enhance the practices of ESL teachers in TAFE Queensland through an online community of practice. The issues of on-the-job training through e-learning for various trades is considered by Anne-Louise Johnston and the benefits and challenges for SkillsTech Australia in developing training partnerships with industry to deliver these changes. These papers were completed by the authors as a part of their postgraduate studies at QUT. The views reported are those of the authors and should not be attributed to the Queensland Department of Education and Training. Donna Berthelsen and Lauren Vogel Faculty of Education Queensland University of Technology December 2009

Osteogenic induction of human bone marrow-derived mesenchymal progenitor cells in novel synthetic polymer-hydrogel matrices

The aim of this project was to investigate the in vitro osteogenic potential of human mesenchymal progenitor cells in novel matrix architectures built by means of a three-dimensional bioresorbable synthetic framework in combination with a hydrogel. Human mesenchymal progenitor cells (hMPCs) were isolated from a human bone marrow aspirate by gradient centrifugation. Before in vitro engineering of scaffold-hMPC constructs, the adipogenic and osteogenic differentiation potential was demonstrated by staining of neutral lipids and induction of bone-specific proteins, respectively. After expansion in monolayer cultures, the cells were enzymatically detached and then seeded in combination with a hydrogel into polycaprolactone (PCL) and polycaprolactone-hydroxyapatite (PCL-HA) frameworks. This scaffold design concept is characterized by novel matrix architecture, good mechanical properties, and slow degradation kinetics of the framework and a biomimetic milieu for cell delivery and proliferation. To induce osteogenic differentiation, the specimens were cultured in an osteogenic cell culture medium and were maintained in vitro for 6 weeks. Cellular distribution and viability within three-dimensional hMPC bone grafts were documented by scanning electron microscopy, cell metabolism assays, and confocal laser microscopy. Secretion of the osteogenic marker molecules type I procollagen and osteocalcin was analyzed by semiquantitative immunocytochemistry assays. Alkaline phosphatase activity was visualized by p-nitrophenyl phosphate substrate reaction. During osteogenic stimulation, hMPCs proliferated toward and onto the PCL and PCL-HA scaffold surfaces and metabolic activity increased, reaching a plateau by day 15. The temporal pattern of bone-related marker molecules produced by in vitro tissue-engineered scaffold-cell constructs revealed that hMPCs differentiated better within the biomimetic matrix architecture along the osteogenic lineage.

Indigenous studies in all schools

Cherbourg State School is approximately 300 km northwest of Brisbane. It is situated in an Aboriginal community at Cherbourg with approximately 250 students. At the Cherbourg State School, the aim was to generate good academic outcomes for all students from kindergarten to Year 7 and to nurture a strong and positive sense of what it means to be Aboriginal in today's society. In this paper, I will discuss modernism and postmodernism in indigenous studies and how this has impacted on the design and development of the Indigenous Studies Programme at the Cherbourg State School. The programme was designed to provide students with the opportunity to learn about the history of Indigenous people from Indigenous voices and provide an understanding of the impact of invasion and the consequences on the lives of Indigenous people, in the past and present. The stories from the elders and members of their own community provided knowledge that allowed students to challenge Aboriginal identity by taking on existing perceptions so that they could be better processed and understood.

Surrogacy - A Path of Obstacles

Surrogacy has become an effective and accepted form of reproductive technology. It enables couples, regardless of gender or sexuality, to achieve the dream of becoming a parent in circumstances where other forms of reproductive technology and adoption are either not possible or have failed. To its credit, the Queensland parliament has recently brought this state up to date by enacting surrogacy laws that are in line with the majority of statutes implemented throughout the country. The Surrogacy Act 2010 (Qld) allows for the court to make a parentage order in certain circumstances where parties have entered into a surrogacy arrangement. A parentage order effectively transfers parental rights from the birth mother (and her spouse or de facto if there is one) to the intended parents. The requirements which must be satisfied to obtain a parenting order are comprehensive and onerous, making the path to parenthood through a surrogacy arrangement by no means easy. At the heart of the surrogacy issue lies a question, the answer to which has shifted and continues to shift as reproductive technologies continue to increase in success, method and popularity - what is a parent? A recent decision of the Administrative Appeals Tribunal, Hudson v Minister for Immigration and Citizenship, brought to attention the meaning of the word ‘parent’ as it appears in s 16(2) Australian Citizenship Act 2007 (Cth) (‘the Act’). Section 16(2) deals with citizenship by descent and provides that a person born outside Australia may make an application to the Minister to become an Australian citizen if a parent of the person was an Australian citizen at the time of the birth.