Genome wide analysis of gene dosage in 24,092 individuals estimates that 10,000 genes modulate cognitive ability

International audienceGenomic copy number variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs > 50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of intelligence quotient when duplicated or deleted, respectively. Effect sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways

SEM Evaluation of the Hybrid Layer in Mechanical and Kinetic Prepared Cavities, Restored with Giomer

Using restorative materials obtained by nanotechnology allows maximum penetration of the dental structures with maximum bond strength both by infiltration and adhesion. The purpose of this study was to analyze with SEM the hybrid layer in enamel and dentin, for the occlusal cavities prepared mechanically and with laser, and filled with giomer. Method The study included 10 human molars and premolars that were extracted for orthodontic or periodontal reasons, which were divided into two equal groups N = 5, each with two equal sub- groups: Group A – cavities in enamel A1 and dentin A2, prepared with laser (WaterlaseMD-Biolase) with MG6- MZ6 peaks, 30% water, 60% air with a power of 5.5 W at 20 Hz for enamel and 3W at 15 Hz for dentine; group B- enamel cavities B1 and dentin cavities B2, both high and low speed mechanical preparations with diamond cylindrical drills and no. 1 globular carbide drills. The materials used were Giomer Beautifil (Shofu), orthophosphoric acid 37%, and dental bonding agent Adper Single Bond Plus (3M ESPE). The materials were placed in a single layer and photo activated with source halogen (3M), cut lengthwise(diamond), polished, conditioned (H3PO4-35% -4s), stored(48 h), analyzed by SEM (VEGAIITESCAN and JEOLJSM 6390ª), SPSS 14.00 statistically analyzed (ANOVA, p ≤ 0.05). Results Hybrid layer analysis showed differences between groups, the average size of the SH being for Gr.A1= 5.18 mm, Gr.A2 = 15.81 mm, Gr.B1=4.24 mm, Gr.B2 = 5.83 mm. There were statistically significant differences between them at p ≤ 0.05, in favour of the samples prepared with laser and examined at the dentin. Conclusions Regardless of the group we studied, adhesion to enamel and dentin of the giomer proved optimal in terms of quality. The advantage in what HL size is concerned belonged to the LASER preparations in dentin

Comparative Evaluation Of The Hybrid Layer In Lateral Preventive Restorations

The purpose of this study was the OM = optical microscopy analysis of the dentinal HL=hybrid layer of two materials with metal alloy particles used in minimally invasive cavity preparations. The study included 10 human premolars and molars, extracted for orthodontic or periodontal reasons. The extracted teeth were used in the study after obtaining a informed consent from the patients, in compliance with the protocol approved by the ethics committee of UMF Gr.T.Popa Iasi. Samples were divided randomly into two equal groups (N = 5): GR.1 (N = 5), GR2 (N = 5). Minimally invasive occlusal cavities were made using a mechanical preparation. We used cylindrical diamond burrs and carbide globular no. 1 burrs. The restorative materials used were: PAA=PolyAcrylic Acid, SE = 3M ™ Scotchbond Etch ™, dental adhesive ASBP = Adper Single Bond Plus (3M ESPE), glass-ionomer with metal alloy particles MM = MIRACLE MIX (3M ESPE) and non gamma 2 amalgam A=ANA2000. The analyzed groups were: GR.1:(5)PAA;MM and GR.2:(5)SE™;ASBP;A. Materials were used according to the manufacturer’s instructions, the resulting samples were thermo cycled 500 cycles (5 0 -55 0), sectioned, viewed by OM=ZEISS–AXIO-CAM-MRC5 and statistically analysed (ANOVA, p ≤ 0.05). Statistical data processing was performed with Microsoft Excel and SPSS 14.0, p ≤ 0, 05. The results obtained by quantitative analysis of the HL indicate that there are differences (p ≤ 0.05) between groups in favour of the samples filled with amalgam 10.37 (± 2.62). Conclusions: The restoration material and the use of a dentinal adhesive dimensionally influence the HL siz