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181.
René Hoehn Tanja Zeller Virginie J. M. Verhoeven Franz Grus Max Adler Roger C. Wolfs André G. Uitterlinden Rapha?le Castagne Arne Schillert Caroline C. W. Klaver Norbert Pfeiffer Alireza Mirshahi 《Human genetics》2012,131(11):1783-1793
Central corneal thickness (CCT) has become an endophenotype of major interest for the genetically complex disorder glaucoma. CCT has a high heritability, and thin CCT is an independent risk factor for the diagnosis and progression of open-angle glaucoma. Genome-wide association studies thus provide genetic loci associated with CCT and potentially related to open-angle glaucoma. The distribution of CCT and prevalence of glaucoma in population-based studies have demonstrated ethnic differences suggesting ethnic-dependent variations in the genetic determinants of CCT. We conducted a genome-wide association study in Caucasians (n?=?3,931) from the Gutenberg Health Study (Germany) followed by replication of 30 genome-wide significant SNPs or SNPs of interest (P?<?10?5) in the Rotterdam Study (The Netherlands, n?=?1,418). In a combined analysis, we confirmed quantitative trait loci on chromosomes 9q34 and 16q24 for association with CCT. On chromosome 16q24, the locus is located in an intergenic region near the ZNF469 gene (top SNP: rs9938149, P?=?1.45?×?10?12). ZNF469 missense mutation is involved in a syndrome with very thin cornea (brittle cornea syndrome). The second locus on chromosome 9q34 represents the intergenic region between the RXRA and COL5A1 gene (top SNP: rs3132306, P?=?2.71?×?10?10). Collagen type 5 determines the diameter of the corneal collagen fibrils. In our Caucasian population-based GWA study, we reinforce the involvement of collagen-related genes influencing CCT in Caucasians. We could not confirm the collagen type 8 locus on chromosome 1 as reported in Asian studies. 相似文献
182.
Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice 总被引:22,自引:0,他引:22
de Klein A Muijtjens M van Os R Verhoeven Y Smit B Carr AM Lehmann AR Hoeijmakers JH 《Current biology : CB》2000,10(8):479-482
Checkpoints of DNA integrity are conserved throughout evolution, as are the kinases ATM (Ataxia Telangiectasia mutated) and ATR (Ataxia- and Rad-related), which are related to phosphatidylinositol (PI) 3-kinase [1] [2] [3]. The ATM gene is not essential, but mutations lead to ataxia telangiectasia (AT), a pleiotropic disorder characterised by radiation sensitivity and cellular checkpoint defects in response to ionising radiation [4] [5] [6]. The ATR gene has not been associated with human syndromes and, structurally, is more closely related to the canonical yeast checkpoint genes rad3(Sp) and MEC1(Sc) [7] [8]. ATR has been implicated in the response to ultraviolet (UV) radiation and blocks to DNA synthesis [8] [9] [10] [11], and may phosphorylate p53 [12] [13], suggesting that ATM and ATR may have similar and, perhaps, complementary roles in cell-cycle control after DNA damage. Here, we report that targeted inactivation of ATR in mice by disruption of the kinase domain leads to early embryonic lethality before embryonic day 8.5 (E8.5). Heterozygous mice were fertile and had no aberrant phenotype, despite a lower ATR mRNA level. No increase was observed in the sensitivity of ATR(+/-) embryonic stem (ES) cells to a variety of DNA-damaging agents. Attempts to target the remaining wild-type ATR allele in heterozygous ATR(+/-) ES cells failed, supporting the idea that loss of both alleles of the ATR gene, even at the ES-cell level, is lethal. Thus, in contrast to the closely related checkpoint gene ATM, ATR has an essential function in early mammalian development. 相似文献
183.
Impact of luxS and Suppressor Mutations on the Gastrointestinal Transit of Lactobacillus rhamnosus GG 下载免费PDF全文
Sarah Lebeer Ingmar J. J. Claes Tine L. A. Verhoeven Chong Shen Ivo Lambrichts Jan L. Ceuppens Jos Vanderleyden Sigrid C. J. De Keersmaecker 《Applied microbiology》2008,74(15):4711-4718
It is generally believed that probiotic bacteria need to survive gastrointestinal transit to exert a health-promoting effect. In this study, a genuine luxS mutant and a luxS mutant containing unknown suppressor mutations of the probiotic strain Lactobacillus rhamnosus GG were compared to the wild type for survival and persistence in the murine gastrointestinal tract. The LuxS enzyme, catalyzing the production of the autoinducer-2 signaling molecule, also forms an integral part of the activated methyl cycle and the metabolism of methionine and cysteine. The genuine luxS mutant CMPG5412 showed drastically reduced persistence in mice, which was related to less survival in simulated gastric juice, indicating that LuxS metabolism is crucial for the gastric stress resistance of L. rhamnosus GG. The suppressor mutations in the other luxS mutant, CMPG5413, appear to compensate for the metabolic defects of the luxS mutation and to restore the resistance to gastric juice but cause a defect in adherence, biofilm formation, and exopolysaccharide production. The shorter residence time of this suppressor mutant in the murine gastrointestinal tract indicates a role for biofilm formation and exopolysaccharides in the persistence capacity of L. rhamnosus GG. 相似文献
184.
Peter J O'Shaughnessy Ana Monteiro Guido Verhoeven Karl De Gendt Margaret H Abel 《Reproductive biology and endocrinology : RB&E》2009,7(1):88-4
Background
Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM. 相似文献185.
Litter N:P ratios indicate whether N or P limits
the decomposability of graminoid leaf litter 总被引:2,自引:0,他引:2
The N:P ratio of leaf litter may determine if decomposability is N-limited (litter with low N:P ratio) or P-limited (litter with high N:P ratio). To test this hypothesis and to determine the threshold between N and P limitation, we studied relationships between litter N and P concentrations, litter mass loss and effects of fertilisation on litter mass loss in laboratory experiments. Leaf litter of 11 graminoid species was collected in Swiss and Dutch wetlands, yielding 84 litter samples with a broad range of N and P concentrations (3.2–15.1 mg N g−1, 0.04–1.93 mg P g−1) and with N:P mass ratios ranging from 5 to 100. On nutrient-free sand, dry mass loss after five or ten weeks (5.5–53% of initial mass) correlated positively with the N and P concentrations of the litter. Within species, mass loss correlated mainly with N for litter with low N:P ratio, and with P for litter with high N:P ratio, in agreement with our hypothesis. Among species, however, these relationships did not exist, and decomposition rather correlated with the specific leaf area. When the litter was incubated on fertilised sand, 35 out of 50 litter samples decomposed faster than on nutrient-free sand. Decomposition was generally accelerated by P fertilisation (i.e. P-limited) when the N:P ratio of the litter was above 25 and the P concentration below 0.22 mg g−1, supporting our hypothesis. N-limited decomposition was not significantly related to the litter N:P ratio but occurred rarely for litter with N:P ratio greater than 25, and only for litter with N concentration below 11.3 mg g−1. We conclude that the N:P ratio of leaf litter indicates whether its decomposability is more likely to be N- or P-limited. The critical N:P ratio (threshold between N and P limitation) appeared to be 25 for graminoid leaf litter. 相似文献
186.
Evolutionary history of the closely related group 2 coronaviruses: porcine hemagglutinating encephalomyelitis virus, bovine coronavirus, and human coronavirus OC43 下载免费PDF全文
Vijgen L Keyaerts E Lemey P Maes P Van Reeth K Nauwynck H Pensaert M Van Ranst M 《Journal of virology》2006,80(14):7270-7274
The close genetic and antigenic relatedness among the group 2 coronaviruses human coronavirus OC43 (HCoV-OC43), bovine coronavirus (BCoV), and porcine hemagglutinating encephalomyelitis virus (PHEV) suggests that these three viruses with different host specificities diverged fairly recently. In this study, we determined the complete genomic sequence of PHEV (strain PHEV-VW572), revealing the presence of a truncated group 2-specific ns2 gene in PHEV in comparison to other group 2 coronaviruses. Using a relaxed molecular clock approach, we reconstructed the evolutionary relationships between PHEV, BCoV, and HCoV-OC43 in real-time units, which indicated relatively recent common ancestors for these species-specific coronaviruses. 相似文献
187.
Is there a second fragrance gene in rice? 总被引:3,自引:0,他引:3
Fitzgerald MA Sackville Hamilton NR Calingacion MN Verhoeven HA Butardo VM 《Plant biotechnology journal》2008,6(4):416-423
Aromatic rice is highly prized by most rice consumers, and many countries cultivate traditional and improved aromatic varieties. 2-Acetyl-1-pyrroline (2AP) is the major aromatic compound in rice, and is believed to accumulate because of an eight-base-pair (8-bp) deletion in an allele at the fragrance locus. In this study, 2AP was quantified and the presence or absence of the fragrance allele ( fgr ) was determined in 464 samples of traditional varieties of rice from the T.T. Chang Genetic Resources Centre at the International Rice Research Institute. It was shown that a number of aromatic varieties, primarily from South and South-East Asia, do not carry the 8-bp deletion, but 2AP was identified in both raw and cooked rice of these varieties. We suggest that the 8-bp deletion in fgr is not the only cause of aroma, and at least one other mutation drives the accumulation of 2AP. The amount of 2AP in most uniform fgr genotypes was not significantly different from that in aromatic n fgr genotypes, but several fgr genotypes, primarily from South Asia, reproducibly accumulated exceptionally large amounts of 2AP. We suggest that the mutation leading to 2AP in aromatic n fgr varieties possibly originated several times and, through either domestication or evolution, the fgr gene and other alleles leading to 2AP have combined in South Asia, leading to several highly aromatic traditional varieties. The identification of multiple mutations for 2AP will enable rice breeding programmes to select actively for multiple genetic sources of 2AP, leading to the development of highly aromatic and, consequently, high-quality varieties of rice. 相似文献
188.
189.
190.
Braeken K Daniels R Vos K Fauvart M Bachaspatimayum D Vanderleyden J Michiels J 《Microbial ecology》2008,55(1):54-64
Swarming motility is considered to be a social phenomenon that enables groups of bacteria to move coordinately atop solid
surfaces. The differentiated swarmer cell population is embedded in an extracellular slime layer, and the phenomenon has previously
been linked with biofilm formation and virulence. The gram-negative nitrogen-fixing soil bacterium Rhizobium etli CNPAF512 was previously shown to display swarming behavior on soft agar plates. In a search for novel genetic determinants
of swarming, a detailed analysis of the swarming behavior of 700 miniTn5 mutants of R. etli was performed. Twenty-four mutants defective in swarming or displaying abnormal swarming patterns were identified and could
be divided into three groups based on their swarming pattern. Fourteen mutants were completely swarming deficient, five mutants
showed an atypical swarming pattern with no completely smooth edge and local extrusions, and five mutants displayed an intermediate
swarming phenotype. Sequence analysis of the targeted genes indicated that the mutants were likely affected in quorum-sensing,
polysaccharide composition or export, motility, and amino acid and polyamines metabolism. Several of the identified mutants
displayed a reduced symbiotic nitrogen fixation activity. 相似文献