排序方式: 共有14条查询结果,搜索用时 31 毫秒
1.
Thibault ST Singer MA Miyazaki WY Milash B Dompe NA Singh CM Buchholz R Demsky M Fawcett R Francis-Lang HL Ryner L Cheung LM Chong A Erickson C Fisher WW Greer K Hartouni SR Howie E Jakkula L Joo D Killpack K Laufer A Mazzotta J Smith RD Stevens LM Stuber C Tan LR Ventura R Woo A Zakrajsek I Zhao L Chen F Swimmer C Kopczynski C Duyk G Winberg ML Margolis J 《Nature genetics》2004,36(3):283-287
With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences. 相似文献
2.
Griffith CA Lora JM Turner J Penteado PF Brown RH Tomasko MG Doose L See C 《Nature》2012,486(7402):237-239
Titan has clouds, rain and lakes--like Earth--but composed of methane rather than water. Unlike Earth, most of the condensable methane (the equivalent of 5?m depth globally averaged) lies in the atmosphere. Liquid detected on the surface (about 2?m deep) has been found by radar images only poleward of 50° latitude, while dune fields pervade the tropics. General circulation models explain this dichotomy, predicting that methane efficiently migrates to the poles from these lower latitudes. Here we report an analysis of near-infrared spectral images of the region between 20°?N and 20°?S latitude. The data reveal that the lowest fluxes in seven wavelength bands that probe Titan's surface occur in an oval region of about 60?×?40?km(2), which has been observed repeatedly since 2004. Radiative transfer analyses demonstrate that the resulting spectrum is consistent with a black surface, indicative of liquid methane on the surface. Enduring low-latitude lakes are best explained as supplied by subterranean sources (within the last 10,000 years), which may be responsible for Titan's methane, the continual photochemical depletion of which furnishes Titan's organic chemistry. 相似文献
3.
Muzny DM Scherer SE Kaul R Wang J Yu J Sudbrak R Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Wei S Wheeler DA Wright MW Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clendenning J Clerc-Blankenburg KP Chen R Chen Z Davis C Delgado O Dinh HH Dong W 《Nature》2006,440(7088):1194-1198
After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. 相似文献
4.
Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome 总被引:1,自引:0,他引:1
Parks AL Cook KR Belvin M Dompe NA Fawcett R Huppert K Tan LR Winter CG Bogart KP Deal JE Deal-Herr ME Grant D Marcinko M Miyazaki WY Robertson S Shaw KJ Tabios M Vysotskaia V Zhao L Andrade RS Edgar KA Howie E Killpack K Milash B Norton A Thao D Whittaker K Winner MA Friedman L Margolis J Singer MA Kopczynski C Curtis D Kaufman TC Plowman GD Duyk G Francis-Lang HL 《Nature genetics》2004,36(3):288-292
In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task. 相似文献
5.
Mailman MD Feolo M Jin Y Kimura M Tryka K Bagoutdinov R Hao L Kiang A Paschall J Phan L Popova N Pretel S Ziyabari L Lee M Shao Y Wang ZY Sirotkin K Ward M Kholodov M Zbicz K Beck J Kimelman M Shevelev S Preuss D Yaschenko E Graeff A Ostell J Sherry ST 《Nature genetics》2007,39(10):1181-1186
The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data. 相似文献
6.
Helminth parasites of white - tailed jackrabbits, Lepus townsendi , were surveyed from southern Wyoming and northwestern Colorado. A total of eight helminth species were identified, including two species of adult cestodes, Mosgovoyia pectinata and M. varabilis ; three species of larval cestodes, Multiceps serialis , Taenia pisiformis , and Taenis sp. ; and three species of nematodes, Dermatoxys veliger , Passalurus ambiguus , and a filariid, Micipsella brevicauda . In addition, eggs of an unidentified species of Nematodirus were found in pooled fecal samples. The cysticercus larva of Taenia sp. is a species new to science and will be reported elsewhere. Mosgovoyia varabilis and Micipsella brevicauda are new records for the white - tailed jackrabbit. 相似文献
7.
Suppression of inflammation by a synthetic histone mimic 总被引:1,自引:0,他引:1
Nicodeme E Jeffrey KL Schaefer U Beinke S Dewell S Chung CW Chandwani R Marazzi I Wilson P Coste H White J Kirilovsky J Rice CM Lora JM Prinjha RK Lee K Tarakhovsky A 《Nature》2010,468(7327):1119-1123
8.
Neale BM Kou Y Liu L Ma'ayan A Samocha KE Sabo A Lin CF Stevens C Wang LS Makarov V Polak P Yoon S Maguire J Crawford EL Campbell NG Geller ET Valladares O Schafer C Liu H Zhao T Cai G Lihm J Dannenfelser R Jabado O Peralta Z Nagaswamy U Muzny D Reid JG Newsham I Wu Y Lewis L Han Y Voight BF Lim E Rossin E Kirby A Flannick J Fromer M Shakir K Fennell T Garimella K Banks E Poplin R Gabriel S DePristo M Wimbish JR Boone BE Levy SE Betancur C Sunyaev S Boerwinkle E Buxbaum JD Cook EH Devlin B 《Nature》2012,485(7397):242-245
Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors. 相似文献
9.
Davis EE Zhang Q Liu Q Diplas BH Davey LM Hartley J Stoetzel C Szymanska K Ramaswami G Logan CV Muzny DM Young AC Wheeler DA Cruz P Morgan M Lewis LR Cherukuri P Maskeri B Hansen NF Mullikin JC Blakesley RW Bouffard GG;NISC Comparative Sequencing Program Gyapay G Rieger S Tönshoff B Kern I Soliman NA Neuhaus TJ Swoboda KJ Kayserili H Gallagher TE Lewis RA Bergmann C Otto EA Saunier S Scambler PJ Beales PL Gleeson JG Maher ER Attié-Bitach T Dollfus H Johnson CA Green ED Gibbs RA Hildebrandt F 《Nature genetics》2011,43(3):189-196
Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ~5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. 相似文献
10.
Puttappa R. Dodmane ? Lora L. Arnold ? Samuel M. Cohen 《科学通报(英文版)》2014,59(11):1078-1082
Inorganic arsenic(iAs) at high doses is a known human carcinogen, inducing tumors of the skin,urinary bladder, and lung. It is also associated with noncancer toxicities. An understanding of the mode of action(MOA) for arsenic-induced effects is needed to develop a scientifically-based risk assessment. To determine an MOA for iAs induced toxicities, it is necessary to understand the metabolism, kinetics, cell transport, and interaction with specific proteins of iAs. Based on in vitro investigations using animal and human cells, studies from animal models,and clinical and epidemiological studies, we have proposed an MOA involving formation of sufficient levels of reactive trivalent metabolites which interact with critical free sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. There is a strong correlation between in vitro cytotoxicity([0.1 lmol/L trivalent arsenicals) and the no effect levels in rodents [approximately 1 ppm(1 ppm = 1 mg/L) of water or diet]. In epithelial target tissues, the cytotoxic effects of iAs result in chronic precursor lesions which have the potential for an increased risk of developing cancer. In non-epithelial tissues, noncancer toxicities such as hypertension and atherosclerosis develop. This MOA implies a non-linear, threshold dose–response relationship for both non-cancer and cancer end points of exposure to iAs. 相似文献