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4277 Functional consequences of the juvenile idiopathic arthritis risk variant at 1q24.3
- Halima Moncrieffe, Katelyn Dunn, Yongbo Huang, Xiaoting Chen, Carl D. Langefeld, Matthew T. Weirauch, John B. Harley, Leah C. Kottyan, Susan D. Thompson, Juvenile Arthritis Consortium for the Immunochip
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 95-96
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- Article
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OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
Chapter 25 - Fire and biodiversity in Australia
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- By John C. Z. Woinarski, Charles Darwin University, Allan H. Burbidge, Department of Parks and Wildlife, Sarah Comer, Department of Parks and Wildlife, Dan Harley, Threatened Species Biologist, Sarah Legge, Suite 5, 280 Hay St, Subiaco, Western Australia, 6008, David B. Lindenmayer, The Australian National University, Canberra, Thalie B. Partridge, Charles Darwin University
- Edited by Adam Stow, Macquarie University, Sydney, Norman Maclean, University of Southampton, Gregory I. Holwell, University of Auckland
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- Book:
- Austral Ark
- Published online:
- 05 November 2014
- Print publication:
- 22 December 2014, pp 537-559
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Summary
Summary
Fire has a major influence on the management and conservation of Australian biodiversity. Notwithstanding a long history of fire on the continent, inappropriate contemporary fire regimes are a key threatening process for many Australian plant and animal species. Fire regimes vary appreciably across the continent, and different species and taxonomic groups respond in markedly different ways to different regimes. A set of case studies highlights the diversity of wildlife responses to fire, although we acknowledge that this set is inevitably far from a comprehensive assessment of the response of all biodiversity components to all fire regimes. Managing fires for biodiversity remains a challenge, particularly in the more remote parts of the continent or when management is driven mostly by human safety and economic assets. Some notable examples of local-and regional-scale fire management programs for biodiversity conservation are presented. Replicating the conservation benefits of these programmes across other parts of Australia will be difficult and will require improved understanding of the fire regimes required by biodiversity, significant effort in implementation and monitoring of outcomes and better understanding of fire by the Australian community.
Introduction
Australia is the most fire-prone continent. Fire has long shaped its ecosystem processes, the juxtaposition and extent of its ecological communities, the structure and floristics of its vegetation types, the ecology of many species, and the distribution, abundance or extinction of individual species. Much of this potency relates to Australian climatic regimes and Australia’s relative lack of topographic relief (and hence protection from extensive fire). Marked wet–dry (monsoonal) seasonality characterises Australia’s north, catalysing frequent (but relatively low-intensity) fire as the annual crop of tall savanna grasses cures during the long dry season. There is marked seasonality also in the Mediterranean and temperate climates of south-eastern and south-western Australia, and their hot summers prompt high-intensity wildfires. Seasonality is less pronounced in the arid inland areas, but recurring but irregular patterns of drought and wet periods drive infrequent but extensive fires as vegetation biomass built up in high-rainfall years dries when the rains disappear. These differences in environmental settings dictate that the frequency and impacts of fires vary very substantially across the Australian continent (Plate 14; Russell-Smith et al. 2007).