Institution
University of Western Australia
Education•Perth, Western Australia, Australia•
About: University of Western Australia is a education organization based out in Perth, Western Australia, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 29613 authors who have published 87405 publications receiving 3064466 citations. The organization is also known as: UWA & University of WA.
Topics: Population, Poison control, Galaxy, Context (language use), Medicine
Papers published on a yearly basis
Papers
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TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
1,768 citations
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TL;DR: This paper outlines the inconsistencies of existing metrics in the context of multi- object miss-distances for performance evaluation, and proposes a new mathematically and intuitively consistent metric that addresses the drawbacks of current multi-object performance evaluation metrics.
Abstract: The concept of a miss-distance, or error, between a reference quantity and its estimated/controlled value, plays a fundamental role in any filtering/control problem. Yet there is no satisfactory notion of a miss-distance in the well-established field of multi-object filtering. In this paper, we outline the inconsistencies of existing metrics in the context of multi-object miss-distances for performance evaluation. We then propose a new mathematically and intuitively consistent metric that addresses the drawbacks of current multi-object performance evaluation metrics.
1,765 citations
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Garvan Institute of Medical Research1, University of New South Wales2, Bankstown Lidcombe Hospital3, University of Queensland4, Baylor College of Medicine5, Ontario Institute for Cancer Research6, University of Newcastle7, University of Sydney8, Royal North Shore Hospital9, Life Technologies10, St. Vincent's Health System11, Royal Prince Alfred Hospital12, Fremantle Hospital13, Royal Adelaide Hospital14, University of Western Australia15, University of California, Los Angeles16, University Health Network17, Mayo Clinic18, University of Toronto19, Johns Hopkins University20, University of Verona21, University of California, San Francisco22, Houston Methodist Hospital23, Cancer Research UK24, Wellcome Trust Sanger Institute25, University of Minnesota26, Netherlands Cancer Institute27
TL;DR: It is found that frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, are also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement ofAxon guidance genes in pancreatic carcinogenesis.
Abstract: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
1,752 citations
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University of Évry Val d'Essonne1, Crops Research Institute2, Agriculture and Agri-Food Canada3, J. Craig Venter Institute4, Fujian Agriculture and Forestry University5, Plant Genome Mapping Laboratory6, University of Giessen7, French Alternative Energies and Atomic Energy Commission8, Institut national de la recherche agronomique9, National Research Council10, Australian Centre for Plant Functional Genomics11, University of Cologne12, Purdue University13, University of California, Berkeley14, University of British Columbia15, Fondation Jean Dausset Centre d'Etude du Polymorphisme Humain16, Huazhong Agricultural University17, Hunan Agricultural University18, Chungnam National University19, University of Arizona20, University of York21, University of Missouri22, Southern Cross University23, University of Western Australia24, Centre national de la recherche scientifique25
TL;DR: The polyploid genome of Brassica napus, which originated from a recent combination of two distinct genomes approximately 7500 years ago and gave rise to the crops of rape oilseed, is sequenced.
Abstract: Oilseed rape (Brassica napus L.) was formed ~7500 years ago by hybridization between B. rapa and B. oleracea, followed by chromosome doubling, a process known as allopolyploidy. Together with more ancient polyploidizations, this conferred an aggregate 72× genome multiplication since the origin of angiosperms and high gene content. We examined the B. napus genome and the consequences of its recent duplication. The constituent An and Cn subgenomes are engaged in subtle structural, functional, and epigenetic cross-talk, with abundant homeologous exchanges. Incipient gene loss and expression divergence have begun. Selection in B. napus oilseed types has accelerated the loss of glucosinolate genes, while preserving expansion of oil biosynthesis genes. These processes provide insights into allopolyploid evolution and its relationship with crop domestication and improvement.
1,743 citations
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TL;DR: The health sector has had its main impact in the area of dementia by providing skills and expertise necessary for comprehensive, holistic assessments, but Kitwood challenges this medical model.
Abstract: Tom Kitwood
Open University Press, £14.95, pp 176
ISBN 0335198554
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The burden of dementia is borne not only by people with dementia, but by their carers, both informal and professional. The major direct financial costs are managed by the welfare sector, through the provision of community services and residential care, whereas indirect costs are largely attributed to informal carers. Advances in care practices would be of considerable benefit. The health sector has had its main impact in the area of dementia by providing skills and expertise necessary for comprehensive, holistic assessments. Kitwood challenges this medical model, which he labels as …
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1,719 citations
Authors
Showing all 29972 results
Name | H-index | Papers | Citations |
---|---|---|---|
Nicholas G. Martin | 192 | 1770 | 161952 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Steven N. Blair | 165 | 879 | 132929 |
David W. Bates | 159 | 1239 | 116698 |
Mark E. Cooper | 158 | 1463 | 124887 |
David Cameron | 154 | 1586 | 126067 |
Stephen T. Holgate | 142 | 870 | 82345 |
Jeremy K. Nicholson | 141 | 773 | 80275 |
Xin Chen | 139 | 1008 | 113088 |
Graeme J. Hankey | 137 | 844 | 143373 |
David Stuart | 136 | 1665 | 103759 |
Joachim Heinrich | 136 | 1309 | 76887 |
Carlos M. Duarte | 132 | 1173 | 86672 |
David Smith | 129 | 2184 | 100917 |