Genetics

MU2A--reconciling the genome and transcriptome to determine the effects of base substitutions.

MOTIVATION: Next-generation sequencing technologies enable the identification of sequence variation in the genome and transcriptome. Differences between the reference genome and transcript libraries complicate the determination of the effect of …

PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells.

BRAF(V600E/K) is a frequent mutationally active tumor-specific kinase in melanomas that is currently targeted for therapy by the specific inhibitor PLX4032. Our studies with melanoma tumor cells that are BRAF(V600E/K) and BRAF(WT) showed that, …

Genome-wide methylation and expression profiling identifies promoter characteristics affecting demethylation-induced gene up-regulation in melanoma.

BACKGROUND: Abberant DNA methylation at CpG dinucleotides represents a common mechanism of transcriptional silencing in cancer. Since CpG methylation is a reversible event, tumor supressor genes that have undergone silencing through this mechanism …

Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implications.

Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It is commonly recognized that to overcome resistance …

Proteomic-based detection of a protein cluster dysregulated during cardiovascular development identifies biomarkers of congenital heart defects.

BACKGROUND: Cardiovascular development is vital for embryonic survival and growth. Early gestation embryo loss or malformation has been linked to yolk sac vasculopathy and congenital heart defects (CHDs). However, the molecular pathways that underlie …

MEDME: an experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment.

DNA methylation is an important component of epigenetic modifications that influences the transcriptional machinery and is aberrant in many human diseases. Several methods have been developed to map DNA methylation for either limited regions or …

Genomewide linkage scan for nicotine dependence: identification of a chromosome 5 risk locus.

BACKGROUND: Nicotine dependence (ND) is costly to societies worldwide, moderately heritable, and genetically complex. Risk loci can be identified with genetic linkage analysis independent of prior physiological hypotheses. METHODS: We completed a …

Molecular triangulation: bridging linkage and molecular-network information for identifying candidate genes in Alzheimer's disease.

A major challenge in human genetics is identifying the molecular basis of common heritable disorders. In contrast to rare single-gene diseases, multifactorial disorders are thought to arise from the combined effect of multiple gene variants, such …