Genetics in the Third Millennium
Volume:10 Issue: 2, 2012

Array based comparative genomic hybridization has been recommended as first tier diagnostic test by The International Standard Cytogenomic Association for individuals with intellectual/developmental delay, multiple congenital anomalies and or autism spectrum disorders. This recommendation was based on analysis of results of multicenter studies and publications on a variety of patient cohorts. It was shown that the application of microarray technology increased detection of genomici imbalances in these patients by 5-10% in comparison to former techniques including karytoypting, MLPA or both. We are reporting the application of this technique to the study of 167 patients with intellectual/developmental delay and/or multiple congenital anomalies to deteerming the efficacy of the technique in Iranian patients. We found that 20.5% of the samples carried possible pathogenic imbalances. We compared this data with results of same patients following MLPA, karyotyping or both. The results indicate that application of the technique increased the detection rate in patients by various degrees based on the initial tests or combinations used. Also we were able to demonstrate that array CGH was effective in detecting mosaicism, in characterizing marker chromosomes and also in fine tuning breakpoints. We believe that array CGH is an effective and plausible alternative to karyotyping, MLPA and FISH and that it provies a more universal screening in one attempt.

Colorectal cancers (CRCs) tumors are diagnosed by microsatellite instability (MSI) due to accumulation of insertion/deletion mutations in tandem repeats of short DNA motifs (1 - 6bp) called microsatellites.Microsatellite instability (MSI) is not only a halkmark marker for screening of hereditary nonpolyposis colorectal cancer(HNPCC),but also a prognostic and predictive marker for sporadic colorectal cancer.Our objective was to determine and study the status of five mononucleotide microsatellite status among Iranian patients with sporadic colorectal cancer. In the current investigation 80 sporadic CRC patients were evaluated for MSI. The pentaplex panel consisting of 5 quasi mononucleotide microsatellite markers (NR-21,BAT-26,BAT-25,NR-27 and NR-24) was used. Our findings reveals that the NR-21 was the most frequent unnstable marker among the other markers (23%).69.6% of specimens had instability in sporadic colorectal cancer.Furthermore,the frequency of instability BAT-25 was determined in 20% sporadic CRC samples. Interestingly our results demonstrated that the frequency of instability NR-24 was 20% that was so close to istability of BAT-25 Marker. Moreover,percentage of NR-27 was 0% in sporadic CRC.Finally, we could find 6.6% instability for BAT-26 in sporadic cases. It seems that among 5 mononucleotide markers NR-21 was the most useful marker for determining the status of sporadic colorectal cancer.Following NR-21,BAT-25 and NR-24 are the most effective markers.Therefore using a triple panel consisting 3 mentioned MSI markers shoud be more promising markers for identifying MSI status in patients with sporadic colorectal cancer.

Liver X Receptors (LXRs) belong to the ligand activated transcription factors of nuclear hormonal superreceptors family which regulate the expression of involved genes in cholesterol homeostasis and act as sterol (cholesterols) sensors which they prevent the cellular cholesterol overload.Activation of LXRslead to themodulation of respective genes expression.To examine the effect of endurance training on lipid profile expression level of LXRα gene, twelve male wistar rats were divided into control (n=6) and Training (n=6) groups. Training group were received exercise on a motor-driven treadmill at 28 m/min (0% grade) for 60 min/day, 5 days/week for 8 weeks. Twenty-four hours after the last exercise session (eighth week), the rats were anesthetized intraperitoneally with a mixture ketamine and xylazine. The mount of blood was taken from the right ventricle of each rat and immediately a part liver were excised and for extraction of LXR RNA Then the frozen tissue was put into -80 °C freezer for mRNA condensation. All variables were compared by independent T-test. Date conducted significant increase in LXR gene expression (70%) and HDL-c (P=0.001) and also the significant decrease in LDL-c, TG, and TC (P=0.001) compared with those in the control group. It could be concluded that, it a positive mechanism of regular endurance exercise causes an improvement in lipid profile (increase in HDL) modulation of there by causes prevention of the cardiovascular diseases, through an increase in the LXR gene expression which resulted in depletion of the cellular cholesterol.

The antifungal activity of thymol was evaluated using the broth microdilution assay with Saccharomyces cerevisiae. The results indicate that minimum inhibitory concentration (MIC100) for thymol is in the range of 80-100 µg/ml. Chemical-genetic profile analysis was completed with thymol using ~4700 haploid S. cerevisiae gene deletion mutants to find out the mode of action of thymol in the yeast cell. 89 S. cerevisiae deletion mutants with the greatest degree of susceptibility to subinhibitory concentration of thymol (50 µg/ml) were selected by digital analysis. Cellular roles of deleted genes in the most susceptible mutants and gene ontology annotation analysis using online gene profiling software (Profcom, gprofiler and GeneMANIA) indicate that the targets for thymol include pathways involved in telomere length maintenance. Spot test analysis of targeted mutants performed to confirm the accuracy of our large-scale approach to detect drug sensitive mutants. Inhibitory effects of thymol on the genes that are involved in telomere length maintenance probably cause telomere shortening during the cell cycle, apoptosis induction and cell growth inhibition in the yeast cell.

In the last decades, the worldwide increase in Biosphere pollution by industrial activities like mining has driven environmental metal contents to toxic levels. For this reason, the study of the biological heavy metal resistance mechanisms in natural environments is important. Therefore, the gene library as an appropriate molecular tool for the detection of heavy metal resistance genes is developed. To evaluate the environmental variation in gene amplification with primers were designed using two methods and the results compared to obtain the best primer. In the first method, we designed a PCR primer pair to specify to detect zntA P-type ATPase ZntA gene sequences. In the second method, a degenerate primers pair for the consensus region 5 gene frome P-type ATPase family gene in bacteria such as Ralstonia eutropha, Burkholderia pseudomallei, Cupriavidus necator, Pseudomonas syringae and Cupriavidus taiwanensis was designed. Discussion and After detection homology in the NCBI gene bank, the result showed that these degenerate primers can be efficient for amplify metal resistance genes in many bacteria. The design and use of a PCR primer pair as a molecular marker to track bacterial heavy metal resistance determinants, providing an excellent tool for long term analysis of environmental communities exposed to metal pollution.

Telomeres, found at eukaryotic chromosome ends, are made up of tandem DNA repeats(TTAGGG repeats). Telomere is heterochromatic domain and protect the chromosome end from rearrangement, end to end fusion and degradation. In most cells, the number of telomeric repeats is reduced with each cell cycle division. If telomeres are ever completely lost, the exposed chromosome ends are recognized as damaged DNA, activating a DNA damage response that can eventually lead to senescence or apoptosis. Telomerase - the enzyme that maintains telomere length in cells - counteracts telomere erosion and provides some somatic cells an unlimited proliferative potential in vitro.full Investigation of the association between telomere and telomerase can make useful contribution to prevention from human aging, aging syndromes and age related diseases.

FMR (Fragile Mental Retardiation) gene mapped to Xq27.3 (OMIM: 309550). Normal individuals carry 50 CGG trinucleotide repeats in the 5' untranslated region of the FMR gene. Increase of these repeat numbers to more than 200 repeats in patients suffering from fragile X syndrome leads to concomitant hypermethylation of these repeats and the CpG islands in the promoter region of the gene, that finally leads to transcriptional silencing of the FMR gene.FMR protein has two hnRNP K-protein homology (KH) domains and a RGG box (Arg-Gly-Gly) to interact with mRNAs that contain either a G-quartet structure or an U-rich sequences. By these hydrophobic interactions, FMRP exerts its chaperonic role in dendritic mRNA transfer and control local mRNA translation and neural plasticity within dendrites in response to synaptic activity. Stimulation of metabotropic glutamate receptors (mGluRs) in neural cells leads to synaptic local protein synthesis, but FMRP by modulation of miRNA and target mRNA hybridization controls mGluR-stimulated protein synthesis. Therefore, through the opposite function of mGlu receptors and FMRP, in the absence of FMRP in fragile X syndrome, protein synthesis at spines will be exaggerated and they will be abnormally long and appear to be immature.