Papers of the week – GABRA1 and STXBP1 in Dravet, gene therapy & synonymous mutations in cancers

FASTA, FASTQ, SAM, BAM, BWA, GC, GATK, IGV. Phew. Day 2 at the EuroEPINOMICS bioinformatics workshop in Leuven. Usually my work starts after the initial NGS raw data quality control and mapping procedures. Today’s topics are supposed to improve my understanding of sequencing analysis and NGS data interpretation. While we are still struggling, other scientists have done their home work already. Here are some of the remarkable publications from this week.


Biologists, physicians and computer scientist at the EuroEPINOMICS bioinformatics workshop 2014 in Leuven

Dravet syndrome GABRA1 & STXBP1. In the latest version of Neurology Carvill and coworkers report on patients with SCN1A negative Dravet syndrome with de novo mutations in GABRA1 and STXBP1. In addition to extending the phenotype associated with mutations in both genes, the group also identified previous false negative SCN1A mutations.

Gene therapy for Wiskott-Aldrich Syndrome. In the latest issues of Science Braun and colleagues present a comprehensive and long-term survey on 10 patients with Wiskott-Aldrich Syndrome (WAS) treated by hematopoietic stem cell gene therapy (GT). They shows that GT for WAS is feasible and effective but the use of γ-retroviral vectors is associated with a substantial risk of leukemogenesis and additional genetic alterations are introduced in the patients’ cells.

Synonymous mutations in human cancers. In this week’s issue of Cell Supek et al. present evidence that synonymous mutations frequently contribute to human cancers. They demonstrate that the affected motifs regulate splicing and are subsequently associated with changes in oncogene splicing in tumors.

Five Years of GWAS Discovery. Are you interested in the history, problems and outcome of genome-wide association studies? Read this review by Visscher and colleagues published this week in The American Journal of Human Genetics. This review pretty much answers all these questions.

Long ncRNAs in neurological disorders. Our understanding of the noncoding part of the human genome is changing rapidly these days. The last years have shown that the regulation of gene expression is also modified by long non-coding RNAs (ncRNAs). Vucicevic et al. review the diverse regulatory mechanisms of long ncRNAs and translate these in potential pathomechanisms in the latest issue of Frontiers in Genetics.