Study of the serotonin transporter (SLC6A4) and BDNF genes in French patients with non syndromic mental deficiency

<p>Abstract</p> <p>Background</p> <p>Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF) pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (<it>SLC6A4</it>) and the brain-derived neurotrophic factor gene (<it>BDNF</it>), are associated with mental deficiency (MD).</p> <p>Methods</p> <p>We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034) of the <it>SLC6A4 </it>gene and one functional polymorphism (Val66 Met) of the <it>BDNF </it>gene in 98 patients with non-syndromic mental deficiency (NS-MD) and in an ethnically matched control population of 251 individuals.</p> <p>Results</p> <p>We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the <it>SLC6A4 </it>and <it>BDNF </it>genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D') in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed.</p> <p>Conclusion</p> <p>Altogether, results from the present study do not support a role for any of the five functional polymorphisms of <it>SLC6A4 </it>and <it>BDNF </it>genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in <it>BDNF </it>and <it>SLC6A4</it>. However, we suggest that further studies on these two pathways in NS-MD remain necessary.</p

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Effect of the oligodendrocyte myelin glycoprotein (OMgp) on the expansion and neuronal differentiation of rat neural stem cells

The oligodendrocyte myelin glycoprotein (OMgp) inhibits axon regeneration after injury in the adult mammalian central nervous system. However its function during brain development remains largely unknown. The present study aims to analyze a possible role for OMgp during neurogenesis. We showed that neural stem cells (NSC) extracted from the whole mesencephalon of rat embryos (E14) and cultured as free floating neurospheres expressed both OMgp and its receptor Nogo-R1. An over-expression of OMgp affected NSC expansion by reducing cell proliferation, but did not affect their differentiation into neurons. These findings indicate a new role for OMgp during brain development as a possible regulator of neurogenesis. Moreover, they suggest a possible implication for OMG gene in the etiology of neurofibromatosis type 1 forms characterized by a deletion of the NF1 gene locus containing OMG

Effect of the oligodendrocyte myelin glycoprotein (OMgp) on the expansion and neuronal differentiation of rat neural stem cells

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Effects of storage temperature on the quantity and integrity of genomic DNA extracted from mice tissues: A comparison of recovery methods

Efficient extraction of genomic DNA (gDNA) from biological materials found in harsh environments is the first step for successful forensic DNA profiling. This study aimed to evaluate two methods for DNA recovery from animal tissues (livers, muscles), focusing on the best storage temperature for DNA yield in term of quality, quantity, and integrity for use in several downstream molecular techniques. Six male Swiss albino mice were sacrificed, liver and muscle tissues (n=32) were then harvested and stored for one week in different temperatures, -20oC, 4oC, 25oC and 40oC. The conditioned animal tissues were used for DNA extraction by Chelex-100 method or NucleoSpin® Blood and Tissue kit. The extracted gDNA was visualized on 1.5% agarose gel electrophoresis to determine the quality of gDNA and analysed spectrophotometrically to determine the DNA concentration and the purity. Both methods, Chelex-100 and NucleoSpin® Blood and Tissue kit found to be appropriate for yielding high quantity of gDNA, with the Chelex®100 method yielding a greater quantity (P &lt; 0.045) than the kit. At -20oC, 4oC, and 25oC temperatures, the concentration of DNA yield was numerically lower than at 40oC. The NucleoSpin® Blood and Tissue kit produced a higher (P=0.031) purity product than the Chelex-100 method, particularly for muscle tissues. The Chelex-100 method is cheap, fast, effective, and is a crucial tool for yielding DNA from animal tissues (livers, muscles) exposed to harsh environment with little limitations.Keywords: DNA degradation, DNA extraction, DNA profiling, Purity, Temperatur

Mutation screening of the ubiquitin ligase gene RNF135 in French patients with autism

International audienceMany genes are now thought to confer susceptibility to autism. Despite the fact that this neuropsychiatric disease appears to be related to several different causes, common cellular and molecular pathways have emerged and point to synaptic dysfunction or cellular growth. Several studies have indicated the importance of the ubiquitin pathway in synaptic function and the aetiology of autism. Here, we focused on the ring finger protein 135 (RNF135) gene, encoding an E3 ubiquitin ligase expressed in the cortex and cerebellum, and located in the NF1 gene locus in 17q11.2, a region linked to autism. We carried out a genetic analysis of the coding sequence of RFN135 in a French cohort of patients with autism and observed a significantly increased frequency of genotypes carrying the rare allele of the rs111902263 (p.R115K) missense variant in patients (P=0.0019, odds ratio : 4.23, 95% confidence interval : 1.87-9.57). Particularly, three unrelated patients showed a homozygous genotype for K115, a situation not observed in the 1812 control individuals. Further cellular and molecular studies are required to elucidate the role of this gene and the variant K115 in brain development and neuronal function