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61.
Hillier LW Fulton RS Fulton LA Graves TA Pepin KH Wagner-McPherson C Layman D Maas J Jaeger S Walker R Wylie K Sekhon M Becker MC O'Laughlin MD Schaller ME Fewell GA Delehaunty KD Miner TL Nash WE Cordes M Du H Sun H Edwards J Bradshaw-Cordum H Ali J Andrews S Isak A Vanbrunt A Nguyen C Du F Lamar B Courtney L Kalicki J Ozersky P Bielicki L Scott K Holmes A Harkins R Harris A Strong CM Hou S Tomlinson C Dauphin-Kohlberg S Kozlowicz-Reilly A Leonard S Rohlfing T Rock SM Tin-Wollam AM Abbott A 《Nature》2003,424(6945):157-164
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Vogt G Chapgier A Yang K Chuzhanova N Feinberg J Fieschi C Boisson-Dupuis S Alcais A Filipe-Santos O Bustamante J de Beaucoudrey L Al-Mohsen I Al-Hajjar S Al-Ghonaium A Adimi P Mirsaeidi M Khalilzadeh S Rosenzweig S de la Calle Martin O Bauer TR Puck JM Ochs HD Furthner D Engelhorn C Belohradsky B Mansouri D Holland SM Schreiber RD Abel L Cooper DN Soudais C Casanova JL 《Nature genetics》2005,37(7):692-700
Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate. 相似文献
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65.
Microsurgical studies on human cells and cloning of HeLa cells 总被引:2,自引:0,他引:2
66.
Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome 总被引:1,自引:0,他引:1
Milner JD Brenchley JM Laurence A Freeman AF Hill BJ Elias KM Kanno Y Spalding C Elloumi HZ Paulson ML Davis J Hsu A Asher AI O'Shea J Holland SM Paul WE Douek DC 《Nature》2008,452(7188):773-776
67.
Racusin JL Karpov SV Sokolowski M Granot J Wu XF Pal'shin V Covino S van der Horst AJ Oates SR Schady P Smith RJ Cummings J Starling RL Piotrowski LW Zhang B Evans PA Holland ST Malek K Page MT Vetere L Margutti R Guidorzi C Kamble AP Curran PA Beardmore A Kouveliotou C Mankiewicz L Melandri A O'Brien PT Page KL Piran T Tanvir NR Wrochna G Aptekar RL Barthelmy S Bartolini C Beskin GM Bondar S Bremer M Campana S Castro-Tirado A Cucchiara A Cwiok M D'Avanzo P D'Elia V Valle MD de Ugarte Postigo A 《Nature》2008,455(7210):183-188
Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two-component jet. 相似文献
68.
Hughes JF Skaletsky H Brown LG Pyntikova T Graves T Fulton RS Dugan S Ding Y Buhay CJ Kremitzki C Wang Q Shen H Holder M Villasana D Nazareth LV Cree A Courtney L Veizer J Kotkiewicz H Cho TJ Koutseva N Rozen S Muzny DM Warren WC Gibbs RA Wilson RK Page DC 《Nature》2012,483(7387):82-86
The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection. 相似文献
69.
Jin Y Birlea SA Fain PR Ferrara TM Ben S Riccardi SL Cole JB Gowan K Holland PJ Bennett DC Luiten RM Wolkerstorfer A van der Veen JP Hartmann A Eichner S Schuler G van Geel N Lambert J Kemp EH Gawkrodger DJ Weetman AP Taïeb A Jouary T Ezzedine K Wallace MR McCormack WT Picardo M Leone G Overbeck A Silverberg NB Spritz RA 《Nature genetics》2012,44(6):676-680
We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4.91 × 10(-15)), CD80 (P = 3.78 × 10(-10)), CLNK (P = 1.56 × 10(-8)), BACH2 (P = 2.53 × 10(-8)), SLA (P = 1.58 × 10(-8)), CASP7 (P = 3.56 × 10(-8)), CD44 (P = 1.78 × 10(-9)), IKZF4 (P = 2.75 × 10(-14)), SH2B3 (P = 3.54 × 10(-18)) and TOB2 (P = 6.81 × 10(-10)). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration. 相似文献
70.
Genome-wide association study of quantitative resistance to southern leaf blight in the maize nested association mapping population 总被引:6,自引:0,他引:6
Kump KL Bradbury PJ Wisser RJ Buckler ES Belcher AR Oropeza-Rosas MA Zwonitzer JC Kresovich S McMullen MD Ware D Balint-Kurti PJ Holland JB 《Nature genetics》2011,43(2):163-168
Nested association mapping (NAM) offers power to resolve complex, quantitative traits to their causal loci. The maize NAM population, consisting of 5,000 recombinant inbred lines (RILs) from 25 families representing the global diversity of maize, was evaluated for resistance to southern leaf blight (SLB) disease. Joint-linkage analysis identified 32 quantitative trait loci (QTLs) with predominantly small, additive effects on SLB resistance. Genome-wide association tests of maize HapMap SNPs were conducted by imputing founder SNP genotypes onto the NAM RILs. SNPs both within and outside of QTL intervals were associated with variation for SLB resistance. Many of these SNPs were within or near sequences homologous to genes previously shown to be involved in plant disease resistance. Limited linkage disequilibrium was observed around some SNPs associated with SLB resistance, indicating that the maize NAM population enables high-resolution mapping of some genome regions. 相似文献