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Cécilia G. Maubaret Klelia D. Salpea Casey E. Romanoski Lasse Folkersen Jackie A. Cooper Coralea Stephanou Ka Wah Li Jutta Palmen Anders Hamsten Andrew Neil Jeffrey W. Stephens Aldons J. Lusis Per Eriksson Philippa J. Talmud Steve E. Humphries the Simon Broome Research Group the EARSII consortium 《PloS one》2013,8(12)
Objective
To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.Methods
Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.Results
Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.Conclusion
Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects. 相似文献3.
Mitochondrial DNAs of six morphologically different Phytophthora species were digested with 15 restriction enzymes. The numbers of restriction fragments obtained differed considerably from those theoretically expected for random base distribution. Enzymes with relatively many G and C in their recognition sequences produced significantly larger numbers of fragments. Moreover, fragments generated by most of these enzymes were more often shared by two or more species than those from enzymes with more A and T in their recognition sequence. It is concluded that base distribution in mitochondrial DNA of Phytophthora is heterogeneous,AT-rich stretches occurring scattered over the mitochondrial genome and GC-rich regions present in conserved sequences, presumably genes. A practical consequence for taxonomic RFLP studies is that optimal enzymes can be selected, depending on the desired level of resolution. 相似文献
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The 18S ribosomal RNAs of 21 tetrapods were sequenced and aligned with five
published tetrapod sequences. When the coelacanth was used as an outgroup,
Lissamphibia (living amphibians) and Amniota (amniotes) were found to be
statistically significant monophyletic groups. Although little resolution
was obtained among the lissamphibian taxa, the amniote sequences support a
sister-group relationship between birds and mammals. Portions of the 28S
ribosomal RNA (rRNA) molecule in 11 tetrapods also were sequenced, although
the phylogenetic results were inconclusive. In contrast to previous
studies, deletion or down- weighting of base-paired sites were found to
have little effect on phylogenetic relationships. Molecular evidence for
amniote relationships is reviewed, showing that three genes
(beta-hemoglobin, myoglobin, and 18S rRNA) unambiguously support a
bird-mammal relationship, compared with one gene (histone H2B) that favors
a bird- crocodilian clade. Separate analyses of four other genes (alpha-
crystallin A, alpha-hemoglobin, insulin, and 28S rRNA) and a combined
analysis of all sequence data are inconclusive, in that different groups
are defined in different analyses and none are strongly supported. It is
suggested that until sequences become available from a broader array of
taxa, the molecular evidence is best evaluated at the level of individual
genes, with emphasis placed on those studies with the greatest number of
taxa and sites. When this is done, a bird-mammal relationship is most
strongly supported. When regarded in combination with the morphological
evidence for this association, it must be considered at least as plausible
as a bird-crocodilian relationship.
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Moulinath Acharya Suddhasil Mookherjee Ashima Bhattacharjee Sanjay KD Thakur Arun K Bandyopadhyay Abhijit Sen Subhabrata Chakrabarti Kunal Ray 《BMC molecular biology》2007,8(1):21
Background
We investigated the molecular basis of primary open-angle glaucoma (POAG) using Opticin (OPTC) as a candidate gene on the basis of its expression in the trabecular meshwork cells involved in the disease pathogenesis. Two hundred POAG patients and 100 controls were enrolled in this study. The coding sequence of OPTC was amplified by PCR from genomic DNA of POAG patients, followed by SSCP, DHPLC and DNA sequencing. Subsequent bioinformatic analysis, site-directed mutagenesis, quantitative RT-PCR and western blot experiments were performed to address the functional significance of a 'silent' change in the OPTC coding region while screening for mutations in POAG patients. 相似文献8.
The effect of the administration of the mycotoxins OTA, ZEA and DON alone resp. in combination on animal health and the residue behavior of pigs from 50 – 60 kg living weight over 90 days was investigated in 4 separate studies. Due to its fast metabolisation the administration of 1000 µg DON resp. 250 µg ZEA per kg feed alone or in combination with other mycotoxins does not lead to detectable residues of these mycotoxins in organs and tissues. Therefore these mycotoxins should not be relevant to the consumer.There is an effect of the simultaneous administration of ZEA resp. DON on the metabolisation resp. secretion of OTA. OTA is of relevance from the point of view of residue toxicology. 相似文献
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Masi S Salpea KD Li K Parkar M Nibali L Donos N Patel K Taddei S Deanfield JE D'Aiuto F Humphries SE 《Free radical biology & medicine》2011,50(6):730-735
The aim of this study was to determine leukocyte telomere length (LTL) in individuals with periodontitis and controls, exploring its relationship with systemic inflammation and oxidative stress. Five hundred sixty-three participants were recruited for this case-control study: 356 subjects with and 207 subjects without periodontitis. LTL was measured by a qPCR technique from leukocytes' DNA. Global measures of oxidative stress (reactive oxygen metabolites) and biological antioxidant potential in plasma were performed together with high-sensitivity assays for C-reactive protein (CRP). Leukocyte counts and lipid profiles were performed using standard biochemistry. Cases had higher levels of CRP (2.1±3.7mg/L vs 1.3±5.4mg/L, P<0.001) and reactive oxygen metabolites (378.1±121.1 U Carr vs 277.4±108.6 U Carr, P<0.001) compared to controls. Overall, cases had shorter LTL with respect to controls (1.23±0.42 vs 1.12±0.31T/S ratio, P=0.006), independent of age, gender, ethnicity, and smoking habit. When divided by subgroup of periodontal diagnosis (chronic, n=285; aggressive, n=71), only chronic cases displayed shorter LTL (P=0.01). LTL was negatively correlated with age (P=0.001; R=-0.2), oxidative stress (P=0.008; R=-0.2), and severity of periodontitis (P=0.003; R=-0.2) in both the whole population and the subgroups (cases and controls). We conclude that shorter telomere lengths are associated with a diagnosis of periodontitis and their measures correlate with the oxidative stress and severity of disease. 相似文献
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An anchored restriction-mapping approach applied to the genetic analysis of the Anopheles gambiae malaria vector complex 1 总被引:1,自引:0,他引:1
We introduce here a simple approach for rapidly determining restriction
maps for a number of regions of a genome; this involves "anchoring" a map
with a rare restriction site (in this case the seldom-cutting EagI)
followed by partial digestion of a frequent-cutting enzyme (e.g., Sau 3A).
We applied this technology to five species of the Anopheles gambiae
complex. In a single Southern blot we obtained about a 15-kb restriction
map each for the mtDNA, rRNA gene, and a scnDNA region for each of five
species. Phylogenetic analyses of these regions yield trees at odds with
the more traditional chromosome inversion-based trees. The value of the
approach for systematic purposes is the ease with which several large,
independent regions of the genome can be quickly assayed for molecular
variation.
相似文献