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排序方式: 共有178条查询结果,搜索用时 31 毫秒
51.
52.
Weedon MN Lettre G Freathy RM Lindgren CM Voight BF Perry JR Elliott KS Hackett R Guiducci C Shields B Zeggini E Lango H Lyssenko V Timpson NJ Burtt NP Rayner NW Saxena R Ardlie K Tobias JH Ness AR Ring SM Palmer CN Morris AD Peltonen L Salomaa V;Diabetes Genetics Initiative;Wellcome Trust Case Control Consortium Davey Smith G Groop LC Hattersley AT McCarthy MI Hirschhorn JN Frayling TM 《Nature genetics》2007,39(10):1245-1250
Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P = 4 x 10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P = 3 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height. 相似文献
53.
Harris SR Clarke IN Seth-Smith HM Solomon AW Cutcliffe LT Marsh P Skilton RJ Holland MJ Mabey D Peeling RW Lewis DA Spratt BG Unemo M Persson K Bjartling C Brunham R de Vries HJ Morré SA Speksnijder A Bébéar CM Clerc M de Barbeyrac B Parkhill J Thomson NR 《Nature genetics》2012,44(4):413-9, S1
Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b. 相似文献
54.
Strauss J Zhang Q Verleyen P Huybrechts J Neupert S Predel R Pauwels K Dircksen H 《Cellular and molecular life sciences : CMLS》2011,68(20):3403-3423
We report identification of a beta-type pigment-dispersing hormone (PDH) identical in two water flea species, Daphnia magna and Daphnia pulex. It has been identified by cloning of precursors, chromatographic isolation from tissue extracts followed by immunoassays
and de novo-mass spectrometric sequencing. The peptide is restricted to a complex system of distinct interneurons in the brain
and visual ganglia, but does not occur in neurosecretory cells projecting to neurohemal organs as in decapod crustaceans.
Thirteen neuron types individually identified and reconstructed by immunohistochemistry were almost identical in terms of
positions and projection patterns in both species. Several neurons invade and form plexuses in visual ganglia and major brain
neuropils including the central body. Five neuron types show contralateral pathways and form plexuses in the lateral, dorsal,
or postlateral brain neuropils. Others are local interneurons, and a tritocerebral neuron connects the protocerebrum with
the neuropil of the locomotory second antenna. Two visual ganglia neuron types lateral to the medulla closely resemble insect
medulla lateral circadian clock neurons containing pigment-dispersing factor based upon positional and projectional criteria.
Experiments under 12:12 h light/dark cycles and constant light or darkness conditions showed significant circadian changes
in numbers and activities of one type of medulla lateral PDH neuron with an acrophase in the evening. This simple PDH system
shows striking homologies to PDH systems in decapod crustaceans and well-known clock neurons in several insects, which suggests
evolutionary conservation of an ancient peptidergic interneuronal system that is part of biological clocks. 相似文献
55.
Höglinger GU Melhem NM Dickson DW Sleiman PM Wang LS Klei L Rademakers R de Silva R Litvan I Riley DE van Swieten JC Heutink P Wszolek ZK Uitti RJ Vandrovcova J Hurtig HI Gross RG Maetzler W Goldwurm S Tolosa E Borroni B Pastor P;PSP Genetics Study Group Cantwell LB Han MR Dillman A van der Brug MP Gibbs JR Cookson MR Hernandez DG Singleton AB Farrer MJ Yu CE Golbe LI Revesz T Hardy J Lees AJ Devlin B Hakonarson H Müller U Schellenberg GD 《Nature genetics》2011,43(7):699-705
Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10(-3). We found significant previously unidentified signals (P < 5 × 10(-8)) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. 相似文献
56.
Raychaudhuri S Remmers EF Lee AT Hackett R Guiducci C Burtt NP Gianniny L Korman BD Padyukov L Kurreeman FA Chang M Catanese JJ Ding B Wong S van der Helm-van Mil AH Neale BM Coblyn J Cui J Tak PP Wolbink GJ Crusius JB van der Horst-Bruinsma IE Criswell LA Amos CI Seldin MF Kastner DL Ardlie KG Alfredsson L Costenbader KH Altshuler D Huizinga TW Shadick NA Weinblatt ME de Vries N Worthington J Seielstad M Toes RE Karlson EW Begovich AB Klareskog L Gregersen PK Daly MJ Plenge RM 《Nature genetics》2008,40(10):1216-1223
To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall). 相似文献
57.
Identification of ten loci associated with height highlights new biological pathways in human growth 总被引:1,自引:0,他引:1
Lettre G Jackson AU Gieger C Schumacher FR Berndt SI Sanna S Eyheramendy S Voight BF Butler JL Guiducci C Illig T Hackett R Heid IM Jacobs KB Lyssenko V Uda M;Diabetes Genetics Initiative;FUSION;KORA;Prostate Lung Colorectal Ovarian Cancer Screening Trial;Nurses' Health Study;SardiNIA Boehnke M Chanock SJ Groop LC Hu FB Isomaa B Kraft P Peltonen L Salomaa V Schlessinger D Hunter DJ Hayes RB Abecasis GR Wichmann HE Mohlke KL Hirschhorn JN 《Nature genetics》2008,40(5):584-591
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. 相似文献
58.
59.
Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus 总被引:1,自引:0,他引:1
Nierman WC Pain A Anderson MJ Wortman JR Kim HS Arroyo J Berriman M Abe K Archer DB Bermejo C Bennett J Bowyer P Chen D Collins M Coulsen R Davies R Dyer PS Farman M Fedorova N Fedorova N Feldblyum TV Fischer R Fosker N Fraser A García JL García MJ Goble A Goldman GH Gomi K Griffith-Jones S Gwilliam R Haas B Haas H Harris D Horiuchi H Huang J Humphray S Jiménez J Keller N Khouri H Kitamoto K Kobayashi T Konzack S Kulkarni R Kumagai T Lafon A Lafton A Latgé JP Li W Lord A Lu C Majoros WH May GS 《Nature》2005,438(7071):1151-1156
Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus. 相似文献
60.
Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice 总被引:5,自引:0,他引:5
Davies W Isles A Smith R Karunadasa D Burrmann D Humby T Ojarikre O Biggin C Skuse D Burgoyne P Wilkinson L 《Nature genetics》2005,37(6):625-629
Imprinted genes show differential expression between maternal and paternal alleles as a consequence of epigenetic modification that can result in 'parent-of-origin' effects on phenotypic traits. There is increasing evidence from mouse and human studies that imprinted genes may influence behavior and cognitive functioning. Previous work in girls with Turner syndrome (45,XO) has suggested that there are X-linked parent-of-origin effects on brain development and cognitive functioning, although the interpretation of these data in terms of imprinted gene effects has been questioned. We used a 39,XO mouse model to examine the influence of the parental origin of the X chromosome on cognitive behaviors and expression of X-linked genes in brain. Our findings confirm the existence of X-linked imprinted effects on cognitive processes and identify a new maternally expressed imprinted gene candidate on the X chromosome, Xlr3b, which may be of importance in mediating the behavioral effects. 相似文献