Cost effective assay choice for rare disease study designs

High throughput assays tend to be expensive per subject. Often studies are limited not so much by the number of subjects available as by assay costs, making assay choice a critical issue. We have developed a framework for assay choice that maximises the number of true disease causing mechanisms ‘seen’, given limited resources. Although straightforward, some of the ramifications of our methodology run counter to received wisdom on study design. We illustrate our methodology with examples, and have built a website allowing calculation of quantities of interest to those designing rare disease studies.published_or_final_versio

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

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One thousand plant transcriptomes and the phylogenomics of green plants

Abstract: Green plants (Viridiplantae) include around 450,000–500,000 species1, 2 of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life

De novo mutations associated with sporadic cases of Caudal regresion syndrome

Poster PresentationAim: The identification of de novo disease causing mutations in three Caucasian patients with sporadic Caudal Regression Syndrome (CRS). CRS is a rare and diverse congenital disorder which is characterised by different degrees of agenesis of the caudal spine. Known genetic mutations are only able to explain a fraction of cases and are not accounting for sporadic occurrences or the diversity of the disorder. Methods: Exome sequencing assay was conducted of the three sporadic cases and their biological parents. We targeted rare genetic variants as the underlying cause of CRS as well as de novo mutations. Further we investigated de novo indels, copy number variations (CNV) and compound heterozygosity. Identified mutations were ranked and filtered based on genomic, genetic and statistical features. Results: Sanger sequencing confirmed two different de novo mutations in two cases (detailed results will be presented). In addition, our analysis revealed several potentially causal compound heterozygous mutations which are also under investigation. Conclusion: CRS may be caused by de novo or compound heterozy mutations thus, i) the diversity of the disorder is mirrored in the underlying genetic architecture and its mutations; ii) ranking of compound heterozygous mutations enables identification of candidate genes

Teaching Out-of-Field Internationally

This chapter presents vignettes from six countries regarding the phenomenon of Teaching Across Specialisations (TAS) or as it is often known teaching out-of-field. The vignettes provide an overview of the education system and policies and practices relating to teacher education, certification, recruitment and assignment to subjects or year levels. They also provide insights into how teaching out-of-field is conceptualised, if or how it is officially reported, its extent and importantly, any local, state or national responses to teaching out-of-field. The six countries included are Australia, Germany, Ireland, the United Kingdom, the USA and Indonesia. These countries have been selected because they have the most available published research relating to teaching out-of-field. The vignettes have been written by researchers and academics from each country who is working in the field. The vignettes highlight the need for a nuanced understanding of the phenomenon as it occurs in different contexts including both commonalities and differences. The chapter concludes with an overview of the occurrence of teaching out-of-field from an international perspective and provides a synthesis of the key insights gleaned from the vignettes. These insights are further elaborated in subsequent chapters to facilitate a deeper understanding of the phenomenon