Articles in 2009

Lauri Aaltonen and colleagues show that a region on 8q24 associated with colorectal cancer risk functions as an enhancer and that the risk allele at this locus binds with higher affinity to the Wnt-regulated transcription factor TCF4 (also called TCF7L2), conferring enhanced responsiveness to Wnt signaling.

Thomas Carroll and colleagues show that attenuation of Wnt9b signaling during kidney morphogenesis affects planar cell polarity and causes an increase in tubule diameter. Their analyses suggest that tubule diameter is established by convergent extension movements and subsequently maintained by polarized cell divisions.

Jasper Rine and colleagues examine the silencing of the HML locus in synchronous S. cerevisiae cells at single-cell resolution. They demonstrate that the establishment of silencing under native conditions occurs rapidly, within two cell cycles.

Philip De Jager and colleagues report results of a large genome-wide association and replication study for multiple sclerosis. The work uncovers three new susceptibility loci for MS, including common and rare variants at TNFRSF1A and common variants at IRF8 and CD6.

Shaoguang Li and colleagues identify Alox5 as a key gene that regulates the function of leukemia stem cells but not normal hematopoietic stem cells in mice, highlighting how cancer and normal stem cells distinctly self-renew and differentiate.

Dominic Kwiatkowski and colleagues of the MalariaGEN and the WTCCC consortiums report a genome-wide analysis of severe malaria in The Gambia. They provide guidance for design of GWAS in African populations, and demonstrate the usefulness of multipoint imputation based on population-specific sequencing data.

Shizufumi Ebihara and colleagues report the identification of Usp46 as a quantitative trait gene underlying mouse behavior in the tail suspension and forced swimming tests, which are widely used for assessing depression-like behavior. Usp46 encodes a ubiquitin-specific peptidase.

Daniel Levy and colleagues report a meta-analysis of genome-wide association studies for blood pressure traits as part of the CHARGE consortium, reporting eight loci with replicated association to systolic and/or diastolic blood pressure, with one of these loci also associated to hypertension.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.

Gunter Reuter and colleagues show that the cytosine-5 methyltransferase DNMT2 controls retrotransposon silencing and telomere integrity in somatic cells of Drosophila.

Hyung-Lae Kim and colleagues report a genome-wide association study of quantitative traits of biomedical importance in Koreans. Although some loci were previously detected in European populations, others are new.

Piero Carninci and colleagues report that 6–30% of cap-selected mouse and human RNA transcripts initiate within repetitive elements. They conclude that retrotransposon transcription is far more widespread than first thought and has a major influence on the transcriptional output of mammalian genomes.

John Mattick and Yoshihide Hayashizaki and colleagues report the identifcation of tiny RNAs approximately 18 nucleotides in length that map near transcription start sites in human, chicken and Drosophila genomes. They call them transcription initiation RNAs (tiRNAs) and show that they associate with highly expressed transcripts and sites of RNA polymerase II binding.

Tarpey et al. carry out a large-scale systematic sequencing of the majority of X-chromosome coding exons from 208 families with multiple individuals with mental retardation and a pattern of transmission compatible with X linkage in order to identify XLMR-causative mutations. They find several mutations that appear to be causative in loci already known to be involved in XLMR, as well as new data about those loci, and make inferences about the role of the different classes of variants in these diseases.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

Arne Pfeufer, Aravinda Chakravarti and colleagues from the QTSCD consortium report genetic associations influencing the QT interval duration, a measure of cardiac repolarization which is a risk factor for sudden cardiac death, in five genome-wide association studies.

Christopher Newton-Cheh and colleagues from the QTGEN consortium report genetic associations to the QT interval duration, a measure of cardiac repolarization which is a risk factor for sudden cardiac death, in three genome-wide association studies from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study.

Martin McMahon and colleagues have generated a new mouse model of metastatic melanoma by generating mice with an activating mutation of Braf and deletion of Pten. The mice show metastatic melanoma with 100% penetrance and short latency, and should serve as a useful pre-clinical model in which to evaluate new therapies.

Alexandre Reymond, Henrik Kaessman and colleagues report a high-resolution survey of copy number variation in mice and assess the impact of such variation on gene expression across multiple tissues and strains. They conclude that CNVs substantially influence global transcription, including long-range cis effects extending up to several hundred kilobases.

Timothy Graubert and colleagues report a high-resolution survey of copy number variation in mouse inbred strains and assess the impact of such variation on gene expression. They find that up to 26% of strain-dependent expression variation in hematopoietic stem/progenitor cells is associated with copy number variation.