Evaluation of linkage disequilibrium and its effect on non-parametric multipoint linkage analysis using two high density single-nucleotide polymorphism mapping panels

Genotype data from the Illumina Linkage III SNP panel (n = 4,720 SNPs) and the Affymetrix 10 k mapping array (n = 11,120 SNPs) were used to test the effects of linkage disequilibrium (LD) between SNPs in a linkage analysis in the Collaborative Study on the Genetics of Alcoholism pedigree collection (143 pedigrees; 1,614 individuals). The average r(2 )between adjacent markers across the genetic map was 0.099 ± 0.003 in the Illumina III panel and 0.17 ± 0.003 in the Affymetrix 10 k array. In order to determine the effect of LD between marker loci in a nonparametric multipoint linkage analysis, markers in strong LD with another marker (r(2 )> 0.40) were removed (n = 471 loci in the Illumina panel; n = 1,804 loci in the Affymetrix panel) and the linkage analysis results were compared to the results using the entire marker sets. In all analyses using the ALDX1 phenotype, 8 linkage regions on 5 chromosomes (2, 7, 10, 11, X) were detected (peak markers p < 0.01), and the Illumina panel detected an additional region on chromosome 6. Analysis of the same pedigree set and ALDX1 phenotype using short tandem repeat markers (STRs) resulted in 3 linkage regions on 3 chromosomes (peak markers p < 0.01). These results suggest that in this pedigree set, LD between loci with spacing similar to the SNP panels tested may not significantly affect the overall detection of linkage regions in a genome scan. Moreover, since the data quality and information content are greatly improved in the SNP panels over STR genotyping methods, new linkage regions may be identified due to higher information content and data quality in a dense SNP linkage panel

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

Genome-Wide Association of Implantable Cardioverter-Defibrillator Activation With Life-Threatening Arrhythmias

OBJECTIVES: To identify genetic factors that would be predictive of individuals who require an implantable cardioverter-defibrillator (ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a life-threatening arrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls). BACKGROUND: Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening arrhythmia. Genetic factors may help identify who is most at risk. METHODS: Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling those who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006 Caucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed and their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age was 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for association between genotype at common variants and the phenotype of having an LTA. RESULTS AND CONCLUSIONS: We did not find any associations reaching genome-wide significance, with the strongest association at chromosome 13, rs11856574 at P = 5×10⁻⁶. Loci previously implicated in phenotypes such as QT interval (measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were not found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find common genetic variants of large effect associated with having a LTA in those of European descent. This indicates that common gene variants cannot be used at this time to guide ICD risk-stratification. TRIAL REGISTRATION: ClinicalTrials.gov NCT00664807

Quantifying the burden of rhodesiense sleeping sickness in Urambo district, Tanzania

Sleeping sickness (human African trypanosomiasis - HAT) is a disease transmitted by tsetse flies and is always fatal if left untreated. The disease occurs in foci affecting poor communities with limited access to health service provision and as such the disease is often left undiagnosed, mistaken for more common afflictions. Even if diagnosed, sleeping sickness is costly to treat, both for health services and patients and their families in terms of costs of diagnosis, transport, hospital care, and the prolonged period of convalescence. Here we estimate the health burden of the acute form T. b. rhodesiense sleeping sickness in Urambo District, Tanzania in terms of Disability Adjusted Life Years (DALYs), the yardstick commonly used by policy makers to prioritize disease management practices, representing a year of healthy life lost to disease. In this single district, the burden of the disease over one year was estimated at 979 DALYs and the estimated monetary costs to health services for the 143 treated patients at US$11,841 and to the patients themselves at US$ 3,673 for direct medical costs and US$ 9,781 for indirect non-medical costs. Sleeping sickness thus places a considerable burden on the affected rural communities and health services

Gene expression profiling of human whole blood samples with the Illumina WG-DASL assay

<p>Abstract</p> <p>Background</p> <p>Microarray-based gene expression analysis of peripheral whole blood is a common strategy in the development of clinically relevant biomarker panels for a variety of human diseases. However, the results of such an analysis are often plagued by decreased sensitivity and reliability due to the effects of relatively high levels of globin mRNA in whole blood. Globin reduction assays have been shown to overcome such effects, but they require large amounts of total RNA and may induce distinct gene expression profiles. The Illumina whole genome DASL assay can detect gene expression levels using partially degraded RNA samples and has the potential to detect rare transcripts present in highly heterogeneous whole blood samples without the need for globin reduction. We assessed the utility of the whole genome DASL assay in an analysis of peripheral whole blood gene expression profiles.</p> <p>Results</p> <p>We find that gene expression detection is significantly increased with the use of whole genome DASL compared to the standard IVT-based direct hybridization. Additionally, globin-probe negative whole genome DASL did not exhibit significant improvements over globin-probe positive whole genome DASL. Globin reduction further increases the detection sensitivity and reliability of both whole genome DASL and IVT-based direct hybridization with little effect on raw intensity correlations. Raw intensity correlations between total RNA and globin reduced RNA were 0.955 for IVT-based direct hybridization and 0.979 for whole genome DASL.</p> <p>Conclusions</p> <p>Overall, the detection sensitivity of the whole genome DASL assay is higher than the IVT-based direct hybridization assay, with or without globin reduction, and should be considered in conjunction with globin reduction methods for future blood-based gene expression studies.</p

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015-2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

Aboriginal youth, hip hop and the politics of identification

This paper explores the identity work taking place around contemporary subcultural hip hop amongst Australian indigenous youth in two disadvantaged urban locations. Previous work on Aboriginal hip hop has been attentive to the interface between tradition and modernity. However, existing scholarship has lacked a deeper ethnographic understanding of the dynamics between youth and parent cultures, and the tensions between the two generations. This article is based on research with young hip hop enthusiasts, community activists and educators. It deals with the cultural politics of identification and sees hip hop practice as associated with a process in which Aboriginality is crystallized as a principal affiliation and as offering an account for experiences of social marginalization. Far from being an outlet for expressing a prior or essential Aboriginality, hip hop as cultural practice is associated with the production of particular identifications

Tar DNA-binding protein-43 (TDP-43) regulates axon growth in vitro and in vivo

Intracellular inclusions of the TAR-DNA binding protein 43 (TDP-43) have been reported in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD-TDP). Rare mutations in TARDBP have been linked to both ALS and FTD-TDP suggesting that TDP-43 dysfunction is mechanistic in causing disease. TDP-43 is a predominantly nuclear protein with roles in regulating RNA transcription, splicing, stability and transport. In ALS, TDP-43 aberrantly accumulates in the cytoplasm of motor neurons where it forms aggregates. However it has until recently been unclear whether the toxic effects of TDP-43 involve recruitment to motor axons, and what effects this might have on axonal growth and integrity. Here we use chick embryonic motor neurons, in vivo and in vitro, to model the acute effects of TDP-43. We show that wild-type and two TDP-43 mutant proteins cause toxicity in chick embryonic motor neurons in vivo. Moreover, TDP-43 is increasingly mislocalised to axons over time in vivo, axon growth to peripheral targets is truncated, and expression of neurofilament-associated antigen is reduced relative to control motor neurons. In primary spinal motor neurons in vitro, a progressive translocation of TDP-43 to the cytoplasm occurs over time, similar to that observed in vivo. This coincides with the appearance of cytoplasmic aggregates, a reduction in the axonal length, and cellular toxicity, which was most striking for neurons expressing TDP-43 mutant forms. These observations suggest that the capacity of spinal motor neurons to produce and maintain an axon is compromised by dysregulation of TDP-43 and that the disruption of cytoskeletal integrity may play a role in the pathogenesis of ALS and FTD-TDP

Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14

The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided