OMiR: Identification of associations between OMIM diseases and microRNAs

AbstractA large number of loci for genetic diseases have been mapped on the human genome and a group of hereditary diseases among them have thus far proven unsuccessful to clone. It is conceivable that such "unclonable" diseases are not linked to abnormalities of protein coding genes (PCGs), but of non-coding RNAs (ncRNAs). We developed a novel approach termed OMiR (OMIM and miRNAs), to test whether microRNAs (miRNAs) exhibit any associations with mapped genetic diseases not yet associated with a PCG. We found that "orphan" genetic disease loci were proximal to miRNA loci more frequently than to loci for which the responsible protein coding gene is known, thus suggesting that miRNAs might be the elusive culprits. Our findings indicate that inclusion of miRNAs among the candidate genes to be considered could assist geneticists in their hunt for disease genes, particularly in the case of rare diseases

Compatible solutes from hyperthermophiles improve the quality of DNA microarrays

<p>Abstract</p> <p>Background</p> <p>DNA microarrays are among the most widely used technical platforms for DNA and RNA studies, and issues related to microarrays sensitivity and specificity are therefore of general importance in life sciences. Compatible solutes are derived from hyperthermophilic microorganisms and allow such microorganisms to survive in environmental and stressful conditions. Compatible solutes show stabilization effects towards biological macromolecules, including DNA.</p> <p>Results</p> <p>We report here that compatible solutes from hyperthermophiles increased the performance of the hybridization buffer for Affymetrix GeneChip^®arrays. The experimental setup included independent hybridizations with constant RNA over a wide range of compatible solute concentrations. The dependence of array quality and compatible solute was assessed using specialized statistical tools provided by both the proprietary Affymetrix quality control system and the open source Bioconductor suite.</p> <p>Conclusion</p> <p>Low concentration (10 to 25 mM) of hydroxyectoine, potassium mannosylglycerate and potassium diglycerol phosphate in hybridization buffer positively affected hybridization parameters and enhanced microarrays outcome. This finding harbours a strong potential for the improvement of DNA microarray experiments.</p

Genome Wide Identification of Recessive Cancer Genes by Combinatorial Mutation Analysis

We devised a novel procedure to identify human cancer genes acting in a recessive manner. Our strategy was to combine the contributions of the different types of genetic alterations to loss of function: amino-acid substitutions, frame-shifts, gene deletions. We studied over 20,000 genes in 3 Gigabases of coding sequences and 700 array comparative genomic hybridizations. Recessive genes were scored according to nucleotide mismatches under positive selective pressure, frame-shifts and genomic deletions in cancer. Four different tests were combined together yielding a cancer recessive p-value for each studied gene. One hundred and fifty four candidate recessive cancer genes (p-value<1.5×10−7, FDR = 0.39) were identified. Strikingly, the prototypical cancer recessive genes TP53, PTEN and CDKN2A all ranked in the top 0.5% genes. The functions significantly affected by cancer mutations are exactly overlapping those of known cancer genes, with the critical exception for the absence of tyrosine kinases, as expected for a recessive gene-set