Fine-scale population structure analysis of seven local Swiss sheep breeds using genome-wide SNP data

As part of the global sheep Hapmap project, 24 individuals from each of seven indigenous Swiss sheep breeds (Bundner Oberländer sheep (BOS), Engadine Red sheep (ERS), Swiss Black-Brown Mountain sheep (SBS), Swiss Mirror sheep (SMS), Swiss White Alpine (SWA) sheep, Valais Blacknose sheep (VBS) and Valais Red sheep (VRS)), were genotyped using Illumina's Ovine SNP50 BeadChip. In total, 167 animals were subjected to a detailed analysis for genetic diversity using 45193 informative single nucleotide polymorphisms. The results of the phylogenetic analyses supported the known proximity between populations such as VBS and VRS or SMS and SWA. Average genomic relatedness within a breed was found to be 12 percent (BOS), 5 percent (ERS), 9 percent (SBS), 10 percent (SMS), 9 percent (SWA), 12 percent (VBS) and 20 percent (VRS). Furthermore, genomic relationships between breeds were found for single individuals from SWA and SMS, VRS and VBS as well as VRS and BOS. In addition, seven out of 40 indicated parent-offspring pairs could not be confirmed. These results were further supported by results from the genome-wide population cluster analysis. This study provides a better understanding of fine-scale population structures within and between Swiss sheep breeds. This relevant information will help to increase the conservation activities of the local Swiss sheep breed

Discovery, linkage disequilibrium and association analyses of polymorphisms of the immune complement inhibitor, decay-accelerating factor gene (DAF/CD55) in type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells. Decay accelerating factor (DAF, CD55), a glycosylphosphatidylinositol-anchored membrane protein, is a candidate for autoimmune disease susceptibility based on its role in restricting complement activation and evidence that DAF expression modulates the phenotype of mice models for autoimmune disease. In this study, we adopt a linkage disequilibrium (LD) mapping approach to test for an association between the DAF gene and T1D. RESULTS: Initially, we used HapMap II genotype data to examine LD across the DAF region. Additional resequencing was required, identifying 16 novel polymorphisms. Combining both datasets, a LD mapping approach was adopted to test for association with T1D. Seven tag SNPs were selected and genotyped in case-control (3,523 cases and 3,817 controls) and family (725 families) collections. CONCLUSION: We obtained no evidence of association between T1D and the DAF region in two independent collections. In addition, we assessed the impact of using only HapMap II genotypes for the selection of tag SNPs and, based on this study, found that HapMap II genotypes may require additional SNP discovery for comprehensive LD mapping of some genes in common disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Resolving mechanisms of immune-mediated disease in primary CD4 T cells

ABSTRACT Deriving mechanisms of immune-mediated disease from GWAS data remains a formidable challenge, with attempts to identify causal variants being frequently hampered by linkage disequilibrium. To determine whether causal variants could be identified via their functional effects, we adapted a massively-parallel reporter assay for use in primary CD4 T-cells, key effectors of many immune-mediated diseases. Using the results to guide further study, we provide a generalisable framework for resolving disease mechanisms from non-coding associations – illustrated by a locus linked to 6 immune-mediated diseases, where the lead functional variant causally disrupts a super-enhancer within an NF-κB-driven regulatory circuit, triggering unrestrained T-cell activation

Ökologische Fallenwirkung von einjährigen Blühstreifen – Laufkäfer als Ökozeiger

Werden Blühstreifen von Nützlingen und Bestäubern als Nistplatz gebraucht, könnte ein Umbrechen zu einer Zerstörung der Nachkommen führen. Dies würde den Blühstreifen zu einer ökologischen Falle machen. In der vorliegenden Studie konnte die Hypothese einer ökologischen Falle für Nützlinge und Bestäuber jedoch nicht bestätigt werden. Es wurden 35 verschiedene Arten Laufkäfer gefangen, sechs davon stehen auf der Roten Liste

Improving patient outcomes in fibrous dysplasia/McCune-Albright syndrome: an international multidisciplinary workshop to inform an international partnership.

Bone and mineral researc

Widespread seasonal gene expression reveals annual differences in human immunity and physiology.

Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease.The Gambian study providing data for analysis was supported by core funding MC-A760-5QX00 to the International Nutrition Group by the UK Medical Research Council (MRC) and the UK Department for the International Development (DFID) under the MRC/DFID Concordat agreement. This work was supported by the JDRF UK Centre for Diabetes-Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003), the JDRF (9-2011-253), the Wellcome Trust (WT061858/091157), the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC) and the Medical Research Council (MRC) Cusrow Wadia Fund. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007–2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (WT100140). X.C.D. was a University of Cambridge/Wellcome Trust Infection and Immunity PhD student. R.C.F. is funded by a JDRF post-doctoral fellowship (3-2011-374). C.W. and H.G are funded by the Wellcome Trust (WT089989). The BABYDIET study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG ZI-310/14-1 to-4), the JDRF (JDRF 17-2012-16 and 1-2006-665) and the German Center for Diabetes Research (DZD e.V.). E.B. is supported by the DFG Research Center and Cluster of Excellence—Center for Regenerative Therapies Dresden (FZ 111).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150512/ncomms8000/full/ncomms8000.html

T1DBase: update 2011, organization and presentation of large-scale data sets for type 1 diabetes research

T1DBase (http://www.t1dbase.org) is web platform, which supports the type 1 diabetes (T1D) community. It integrates genetic, genomic and expression data relevant to T1D research across mouse, rat and human and presents this to the user as a set of web pages and tools. This update describes the incorporation of new data sets, tools and curation efforts as well as a new website design to simplify site use. New data sets include curated summary data from four genome-wide association studies relevant to T1D, HaemAtlas—a data set and tool to query gene expression levels in haematopoietic cells and a manually curated table of human T1D susceptibility loci, incorporating genetic overlap with other related diseases. These developments will continue to support T1D research and allow easy access to large and complex T1D relevant data sets

Development of an integrated genome informatics, data management and workflow infrastructure: a toolbox for the study of complex disease genetics.

The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D), chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC) and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are