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991.
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Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease 总被引:1,自引:0,他引:1
Trynka G Hunt KA Bockett NA Romanos J Mistry V Szperl A Bakker SF Bardella MT Bhaw-Rosun L Castillejo G de la Concha EG de Almeida RC Dias KR van Diemen CC Dubois PC Duerr RH Edkins S Franke L Fransen K Gutierrez J Heap GA Hrdlickova B Hunt S Izurieta LP Izzo V Joosten LA Langford C Mazzilli MC Mein CA Midah V Mitrovic M Mora B Morelli M Nutland S Núñez C Onengut-Gumuscu S Pearce K Platteel M Polanco I Potter S Ribes-Koninckx C Ricaño-Ponce I Rich SS Rybak A Santiago JL Senapati S Sood A 《Nature genetics》2011,43(12):1193-1201
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease. 相似文献
994.
A rare penetrant mutation in CFH confers high risk of age-related macular degeneration 总被引:1,自引:0,他引:1
995.
Hahn CN Chong CE Carmichael CL Wilkins EJ Brautigan PJ Li XC Babic M Lin M Carmagnac A Lee YK Kok CH Gagliardi L Friend KL Ekert PG Butcher CM Brown AL Lewis ID To LB Timms AE Storek J Moore S Altree M Escher R Bardy PG Suthers GK D'Andrea RJ Horwitz MS Scott HS 《Nature genetics》2011,43(10):1012-1017
996.
miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration 总被引:2,自引:0,他引:2
microRNAs (miRNAs) function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that miRNAs canalize development and provide genetic robustness. Here, we uncover a previously unidentified regulatory layer of chemokine signaling by miRNAs that confers genetic robustness on primordial germ cell (PGC) migration. In zebrafish, PGCs are guided to the gonad by the ligand Sdf1a, which is regulated by the sequestration receptor Cxcr7b. We find that miR-430 regulates sdf1a and cxcr7 mRNAs. Using target protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a (also known as cxcl12a) and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (ii) modulates the levels of the decoy receptor Cxcr7b to avoid excessive depletion of Sdf1a and (iii) buffers against variation in gene dosage of chemokine signaling components to ensure accurate PGC migration. Our results indicate that losing miRNA-mediated regulation can expose otherwise buffered genetic lesions leading to developmental defects. 相似文献
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Dobbins SE Broderick P Melin B Feychting M Johansen C Andersson U Brännström T Schramm J Olver B Lloyd A Ma YP Hosking FJ Lönn S Ahlbom A Henriksson R Schoemaker MJ Hepworth SJ Hoffmann P Mühleisen TW Nöthen MM Moebus S Eisele L Kosteljanetz M Muir K Swerdlow A Simon M Houlston RS 《Nature genetics》2011,43(9):825-827
To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development. 相似文献
1000.
D. J. Eldridge 《西北部美国博物学家》2011,53(1)
Grazed and ungrazed sites were examined in a semiarid woodland in eastern Australia to determine relationships within various types of cryptogams, and the role of cryptogams in pasture dynamics, infiltration, and water erosion. Strong relationships were found between vascular plant cover and cover of cryptogams for nine rangeland sites over an 18-month period. In the absence of vascular plants, sites with low cover of cryptogams were dominated by algae. The presence of a cryptogamic crust had no significant effect on infiltration at ungrazed sites but significantly increased infiltration at some grazed sites. Splash erosion was very low on soils with at least 50% cryptogam cover. Below this level splash erosion increased markedly, along with the proportion of fine sediments lost. 相似文献