Poirier K.,University of Paris Descartes |
Poirier K.,French Institute of Health and Medical Research |
Lebrun N.,University of Paris Descartes |
Lebrun N.,French Institute of Health and Medical Research |
And 45 more authors.
Nature Genetics | Year: 2013
The genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered γ-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD. © 2013 Nature America, Inc. All rights reserved.
Hooton H.,French Institute of Health and Medical Research |
Hooton H.,University Pierre and Marie Curie |
Hooton H.,University of Paris Descartes |
Angquist L.,Copenhagen University |
And 30 more authors.
PLoS ONE | Year: 2012
Background/Aims:Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology-this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors-increased by high protein, glycemic index and energy diets.Methods:Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer-experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6-8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors-energy density, protein content (in grams or in % of total energy intake) and glycemic index-on these four adiposity phenotypes.Results:We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N°2), p = 0.02, β = -0.2446), and waist change over time (rs7511673 (SNP N°1), p = 0.01, β = -0.0433 and rs10888390 (SNP N°3), p = 0.04, β = -0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N°2) was also associated with the risk of being a weight gainer (pinteraction = 0.01, OR = 1.0526)-the risk of being a weight gainer increased with the percentage of proteins contained in the diet.Conclusion:CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake. © 2012 Hooton et al.
O'Leary-Barrett M.,McGill University |
Pihl R.O.,McGill University |
Artiges E.,University Paris - Sud |
Artiges E.,University of Paris Descartes |
And 138 more authors.
PLoS ONE | Year: 2015
Objective: To investigate the role of personality factors and attentional biases towards emotional faces, in establishing concurrent and prospective risk for mental disorder diagnosis in adolescence. Method: Data were obtained as part of the IMAGEN study, conducted across 8 European sites, with a community sample of 2257 adolescents. At 14 years, participants completed an emotional variant of the dot-probe task, as well two personality measures, namely the Substance Use Risk Profile Scale and the revised NEO Personality Inventory. At 14 and 16 years, participants and their parents were interviewed to determine symptoms of mental disorders. Results: Personality traits were general and specific risk indicators for mental disorders at 14 years. Increased specificity was obtained when investigating the likelihood of mental disorders over a 2-year period, with the Substance Use Risk Profile Scale showing incremental validity over the NEO Personality Inventory. Attentional biases to emotional faces did not characterise or predict mental disorders examined in the current sample. Discussion: Personality traits can indicate concurrent and prospective risk for mental disorders in a community youth sample, and identify at-risk youth beyond the impact of baseline symptoms. This study does not support the hypothesis that attentional biases mediate the relationship between personality and psychopathology in a community sample. Task and sample characteristics that contribute to differing results among studies are discussed. © 2015 O'Leary-Barrett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Chaouachi M.,University of Monastir |
Alaya A.,University of Monastir |
Ali I.B.H.,Institute National des science Appliquees |
Hafsa A.B.,University of Monastir |
And 5 more authors.
Plant Cell Reports | Year: 2013
Key message: Here, we describe a new developed quantitative real-time PCR method for the detection and quantification of a new specific endogenous reference gene used in GMO analysis. The key requirement of this study was the identification of a new reference gene used for the differentiation of the four genomic sections of the sugar beet (Beta vulgaris L.) (Beta, Corrollinae, Nanae and Procumbentes) suitable for quantification of genetically modified sugar beet. A specific qualitative polymerase chain reaction (PCR) assay was designed to detect the sugar beet amplifying a region of the adenylate transporter (ant) gene only from the species of the genomic section I of the genus Beta (cultivated and wild relatives) and showing negative PCR results for 7 species of the 3 other sections, 8 related species and 20 non-sugar beet plants. The sensitivity of the assay was 15 haploid genome copies (HGC). A quantitative real-time polymerase chain reaction (QRT-PCR) assay was also performed, having high linearity (R2 > 0. 994) over sugar beet standard concentrations ranging from 20,000 to 10 HGC of the sugar beet DNA per PCR. The QRT-PCR assay described in this study was specific and more sensitive for sugar beet quantification compared to the validated test previously reported in the European Reference Laboratory. This assay is suitable for GMO quantification in routine analysis from a wide variety of matrices. © 2012 Springer-Verlag Berlin Heidelberg.