Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P 1 × 10 5 were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 × 10 17), 16q22 (CDH1 and CDH3; P = 2.8 × 10 8) and 7q31 (LAMB1; P = 3.0 × 10 8). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis. © 2009 Nature America, Inc. All rights reserved.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

The ultimate edge: The case for planning media for sustaining space communities

Governments and intergovernmental organisations have long recognised that space communities – the ultimate ‘settlements at the edge’ – will exist one day and have based their first plans for these on another region ‘at the edge’, the Antarctic. United States President Eisenhower proposed to the United Nations in 1960 that the principles of the Antarctic Treaty be applied to outer space and celestial bodies (State Department, n.d.). Three years later the UN adopted the Declaration of Legal Principles Governing the Activities of States in the Exploration and Use of Outer Space and in 1967 that became the Outer Space Treaty. According to the UN Office for Outer Space Affairs, ‘the Treaty was opened for signature by the three depository Governments (the Russian Federation, the United Kingdom and the United States of America) in January 1967, and it entered into force in October 1967’ (Office for Outer Space Affairs, n.d). The status of the treaty (at time of writing) was 89 signatories and 102 parties (Office for Disarmament Affairs, n.d.). Other related instruments include the Rescue Agreement, the Liability Convention, the Registration Convention and the Moon Agreement (Office for Outer Space Affairs, n.d.-a). Jumping to the present, a newsagency reported in July 2014 (Reuters, 2014) that the British Government had shortlisted eight aerodromes in its search for a potential base for the UK’s first spaceplane flights which Ministers want to happen by 2018 (UK Space Agency, 2014). The United States already has a spaceport, in New Mexico (Cokley, Rankin, Heinrich, & McAuliffe, 2013)...

Contos da Câmara 2 : depoimentos de servidores nos 180 anos do Legislativo

Reúne depoimentos de servidores da Câmara do Deputados sobre os acontecimentos que marcaram a história do parlamento brasileiro a partir da segunda metade do século XX. Coletados pelo Núcleo de História Oral da Câmara durante as comemorações dos 180 anos do Poder Legislativo em 2003, os textos retratam a realidade dos primeiros anos vividos no Planalto Central: a carência de infra-estrutura, a falta de opção de atividades de lazer e o profundo sentimento de saudade da antiga capital da República. Mas também levam a reminiscências de momentos divertidos, curiosidades e reflexões animadas e esperançosas sobre a mudança da capital para Brasília. O ponto alto são as experiências vivenciadas nos prédios do Congresso Nacional, a lembrança dos amigos, dos colegas e, especialmente, dos fatos marcantes, que sublinham as significativas mudanças nas rotinas de trabalho da Instituição para se adequar à modernização e às novas exigências da sociedade, no contexto de acontecimentos políticos que modificaram seguidas vezes o cenário do país.

Cyclical Features of Uzawa-Lucas Endogenous Growth Model

This paper analyzes the cyclical properties of a generalized version of Uzawa-Lucas endogenous growth model. We study the dynamic features of different cyclical components of this model characterized by a variety of decomposition methods. The decomposition methods considered can be classified in two groups. On the one hand, we consider three statistical filters: the Hodrick-Prescott filter, the Baxter-King filter and Gonzalo-Granger decomposition. On the other hand, we use four model-based decomposition methods. The latter decomposition procedures share the property that the cyclical components obtained by these methods preserve the log-linear approximation of the Euler-equation restrictions imposed by the agent’s intertemporal optimization problem. The paper shows that both model dynamics and model performance substantially vary across decomposition methods. A parallel exercise is carried out with a standard real business cycle model. The results should help researchers to better understand the performance of Uzawa-Lucas model in relation to standard business cycle models under alternative definitions of the business cycle.

A study of the proposed Diamond Creek Reservoir

Politically the Colorado river is an interstate as well as an international stream. Physically the basin divides itself distinctly into three sections. The upper section from head waters to the mouth of San Juan comprises about 40 percent of the total of the basin and affords about 87 percent of the total runoff, or an average of about 15 000 000 acre feet per annum. High mountains and cold weather are found in this section. The middle section from the mouth of San Juan to the mouth of the Williams comprises about 35 percent of the total area of the basin and supplies about 7 percent of the annual runoff. Narrow canyons and mild weather prevail in this section. The lower third of the basin is composed of mainly hot arid plains of low altitude. It comprises some 25 percent of the total area of the basin and furnishes about 6 percent of the average annual runoff.

The proposed Diamond Creek reservoir is located in the middle section and is wholly within the boundary of Arizona. The site is at the mouth of Diamond Creek and is only 16 m. from Beach Spring, a station on the Santa Fe railroad. It is solely a power project with a limited storage capacity. The dam which creats the reservoir is of the gravity type to be constructed across the river. The walls and foundation are of granite. For a dam of 290 feet in height, the back water will be about 25 m. up the river.

The power house will be placed right below the dam perpendicular to the axis of the river. It is entirely a concrete structure. The power installation would consist of eighteen 37 500 H.P. vertical, variable head turbines, directly connected to 28 000 kwa. 110 000 v. 3 phase, 60 cycle generators with necessary switching and auxiliary apparatus. Each unit is to be fed by a separate penstock wholly embedded into the masonry.

Concerning the power market, the main electric transmission lines would extend to Prescott, Phoenix, Mesa, Florence etc. The mining regions of the mountains of Arizona would be the most adequate market. The demand of power in the above named places might not be large at present. It will, from the observation of the writer, rapidly increase with the wonderful advancement of all kinds of industrial development.

All these things being comparatively feasible, there is one difficult problem: that is the silt. At the Diamond Creek dam site the average annual silt discharge is about 82 650 acre feet. The geographical conditions, however, will not permit silt deposites right in the reservoir. So this design will be made under the assumption given in Section 4.

The silt condition and the change of lower course of the Colorado are much like those of the Yellow River in China. But one thing is different. On the Colorado most of the canyon walls are of granite, while those on the Yellow are of alluvial loess: so it is very hard, if not impossible, to get a favorable dam site on the lower part. As a visitor to this country, I should like to see the full development of the Colorado: but how about THE YELLOW!

The 1996 U.S. Purse Seine Fishery for Tropical Tunas in the Central-Western Pacific Ocean

The U.S. tropical tuna purse seine fleet has fished the central-western Pacific Ocean under the South Pacific Tuna Treaty since 1988. The 1996 fishery was the poorest since the start ofthe Treaty. Fishing effort declined due to the financial collapse of a large fishing enterprise. Catches reached record lows for yellowfin tuna, Thunnus albacares, and skipjack tuna, Katsuwonus pelamis, and continued a declining trend that started in 1995. Catch rates also decreased to the lowest levels since 1991. Whether this declining trend in catch rates is due to reduced availability of fish caused by cyclic ocean environmental changes affecting vulnerability or to reduced abundance from excessive fishing pressure is not yet known and needs to be assessed.

Report of 2009 Bottlenose Dolphin (Tursiops truncatus) Life History Workshop: expanding network capabilities

The Virginia Aquarium & Marine Science Center Foundation’s Stranding Response Program (VAQS) was awarded a grant in 2008 to conduct life history analysis on over 10 years of Tursiops truncatus teeth and gonad samples from stranded animals in Virginia. A major part of this collaborative grant included a workshop involving life historians from Hubbs-Sea World Research Institute (HSWRI), NOS, Texas A & M University (TAMU), and University of North Carolina Wilmington (UNCW). The workshop was held at the NOAA Center for Coastal Environmental Health & Biomolecular Research in Charleston, SC on 7-9 July 2009. The workshop convened to 1) address current practices among the groups conducting life history analysis, 2) decide on protocols to follow for the collaborative Prescott grant between VAQS and HSWRI, 3) demonstrate tissue preparation techniques and discuss shortcuts and pitfalls, 4) demonstrate data collection from prepared testes, ovaries, and teeth, and 5) discuss data analysis and prepare an outline and timeline for a future manuscript. The workshop concluded with discussions concerning the current collaborative Tursiops Life History Prescott grant award and the beginnings of a collaborative Prescott proposal with members of the Alliance of Marine Mammal Parks and Aquariums to further clarify reproductive analyses. This technical memorandum serves as a record of this workshop.

土壤藻类及其生理生态

<正> 人类对土壤藻类的认识至少可以追溯到三千多年前的我国诗经时代。Prescott引用Porterfield的研究并阐述说:尽管藻类学作为一门科学是由西方文化中诞生的,但最早的文字记载出现在中国的古典著作中,在诗经中人们可以发现采集和食用念珠藻(Nostoc)的文献记录……。他们还提到,古希腊的贤哲对念珠藻也有过观察。但是,尽管十七、十八世纪前后在我国和欧洲对土壤藻类都有了较细微的描述性记录,如我国明代科学

'What Foes more dang'rous than too strong Allies?': Anglo-Welsh relations in eighteenth-century London

Prescott, Sarah, ''What Foes more dang'rous than too strong Allies?': Anglo-Welsh relations in eighteenth-century London', The Huntington Library Quarterly (2006) 69 (4) pp.535-554 RAE2008

The Cambrian Muse: Welsh Identity and Hanoverian Loyalty in the Poems of Jane Brereton (1685-1740)

Prescott, S. (2005). The Cambrian Muse: Welsh Identity and Hanoverian Loyalty in the Poems of Jane Brereton (1685-1740). Eighteenth -Century Studies. 38(4), pp.587-603. RAE2008