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81.
Rachel Knevel Diederik PC de Rooy Tore Saxne Elisabet Lindqvist Martha K Leijsma Nina A Daha Bobby PC Koeleman Roula Tsonaka Jeanine J Houwing-Duistermaat Joris JM Schonkeren Rene EM Toes Tom WJ Huizinga Elisabeth Brouwer Anthony G Wilson Annette HM van der Helm-van Mil 《Arthritis research & therapy》2014,16(3):R108
Introduction
Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA.Methods
1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied.Results
We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10−4). This variant was also significant after Bonferroni correction.Conclusions
These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA. 相似文献82.
The signal produced by fluorescence in situ hybridization (FISH) often is inconsistent among cells and sensitivity is low. Small DNA targets on the chromatin are difficult to detect. We report here an improved nick translation procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes. Brighter probes can be obtained by adding excess DNA polymerase I. Using such probes, a 30 kb yeast transgene, and the rp1, rp3 and zein multigene clusters were clearly detected. 相似文献
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18S rRNA data indicate that Aschelminthes are polyphyletic in origin and consist of at least three distinct clades 总被引:7,自引:1,他引:6
Winnepenninckx B; Backeljau T; Mackey LY; Brooks JM; De Wachter R; Kumar S; Garey JR 《Molecular biology and evolution》1995,12(6):1132-1137
The Aschelminthes is a collection of at least eight animal phyla,
historically grouped together because the absence of a true body cavity was
perceived as a pseudocoelom. Analyses of 18S rRNA sequences from six
Aschelminth phyla (including four previously unpublished sequences) support
polyphyly for the Aschelminthes. At least three distinct groups of
Aschelminthes were detected: the Priapulida among the protostomes, the
Rotifera-Acanthocephala as a sister group to the protostomes, and the
Nematoda as a basal group to the triploblastic Eumetazoa.
相似文献
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Host‐targeted RAD‐Seq reveals genetic changes in the coral Oculina patagonica associated with range expansion along the Spanish Mediterranean coast
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Karine Posbic Leydet Carsten G. B. Grupstra Rafel Coma Marta Ribes Michael E. Hellberg 《Molecular ecology》2018,27(11):2529-2543
Many organisms are expanding their ranges in response to changing environmental conditions. Understanding the patterns of genetic diversity and adaptation along an expansion front is crucial to assessing a species’ long‐term success. While next‐generation sequencing techniques can reveal these changes in fine detail, ascribing them to a particular species can be difficult for organisms that live in close association with symbionts. Using a novel modified restriction site‐associated DNA sequencing (RAD‐Seq) protocol to target coral DNA, we collected 595 coral‐specific single nucleotide polymorphisms from 189 colonies of the invasive coral Oculina patagonica from the Spanish Mediterranean coast, including established core populations and two expansion fronts. Surprisingly, populations from the recent northern expansion are genetically distinct from the westward expansion and core populations and also harbour greater genetic diversity. We found that temperature may have driven adaptation along the northern expansion, as genome scans for selection found three candidate loci associated with temperature in the north but none in the west. We found no genomic signature of selection associated with artificial substrate, which has been proposed for explaining the rapid spread of O. patagonica. This suggests that this coral is simply an opportunistic colonizer of free space made available by coastal habitat modifications. Our results suggest that unique genetic variation, possibly due to limited dispersal across the Ibiza Channel, an influx of individuals from different depths and/or adaptation to cooler temperatures along the northern expansion front may have facilitated the northward range expansion of O. patagonica in the western Mediterranean. 相似文献
90.
The Molecular Basis of Canavan (Aspartoacylase Deficiency) Disease in European Non-Jewish Patients 总被引:3,自引:1,他引:2
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A. Shaag Y. Anikster E. Christensen J. Z. Glustein A. Fois H. Michelakakis F. Nigro E. Pronicka A. Ribes M. T. Zabot O. N. Elpeleg 《American journal of human genetics》1995,57(3):572-580
Canavan disease is an infantile neurodegenerative disease that is due to aspartoacylase deficiency. The disease has been reported mainly in Ashkenazi Jews but also occurs in other ethnic groups. Determination of enzymatic activity for carrier detection and prenatal diagnosis is considered unreliable. In the present study, nine mutations were found in the aspartoacylase gene of 19 non-Jewish patients. These included four point mutations (A305E [39.5% of the mutated alleles], C218X [15.8%], F295S [2.6%], and G274R [5.3%]); four deletion mutations (827delGT [5.3%], 870del4 [2.6%], 566del7 [2.6%], and 527del6 [2.6%]); and one exon skip (527del108 [5.3%]). The A305E mutation is pan-European and probably the most ancient mutation, identified in patients of Greek, Polish, Danish, French, Spanish, Italian, and British origin. In contrast, the G274R and 527del108 mutations were found only in patients of Turkish origin, and the C218X mutation was identified only in patients of Gypsy origin. Homozygosity for the A305E mutation was identified in patients with both the severe and the mild forms of Canavan disease. Mutations were identified in 31 of the 38 alleles, resulting in an overall detection rate of 81.6%. All nine mutations identified in non-Jewish patients reside in exons 4–6 of the aspartoacylase gene. The results would enable accurate genetic counseling in the families of 13 (68.4%) of 19 patients, in whom two mutations were identified in the aspartoacylase cDNA. 相似文献