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This Week in PNAS: Dec 22, 2010

In PNAS this week, researchers at McGill University in Montreal suggest that analysis of partial variance of genes' translational levels in genome-wide studies is a better alternative to trying to identify differential translation independent of cytosolic mRNA levels as genome-wide analyses of translational control currently do. "When combined with a variance shrinkage method for estimating error variance, analysis of partial variance has the additional benefit of having greater statistical power and identifying fewer genes as translationally regulated resulting merely from unrealistically low variance estimates rather than from large changes in translational activity," the researchers write.

Also in PNAS this week, researchers in Italy use a combination of pathology tissue-chromatin immunoprecipitation and high-throughput sequencing to determine the epigenetic profile of patient samples. This PAT-ChIP methodology allows researchers to get around the problems normally presented by paraffin-embedded patient samples, and works on samples that are several years old, the researchers write. PAT-ChIP showed a high reproducibility of results for several histone marks compared to canonical ChIP, and also showed an identical ability to detect dynamic changes in chromatic structure upon pharmacological treatment, the team says, and can be combined with high-throughput sequencing for GWAS of chromatin modifications.

A group of researchers in Massachusetts say that microRNA miR-125b causes several kinds of leukemia. To decipher the oncogenic mechanism of miR-125b, Bousquet et al. transplanted mice with fetal liver cells — those transplanted with cells ectopically expressing miR-125b showed an increase in white blood cell counts, and about half of these mice died of B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, or a myeloproliferative neoplasm. This, the researchers write, suggests "an important role for miR-125b in early hematopoiesis." Co-expression of miR-125b and the BCR-ABL fusion gene in transplanted cells also accelerated the development of leukemia in mice, compared with controls expressing only BCR-ABL, the team adds.

And in another PNAS paper on miR-125b's oncogenic effects, researchers at Stanford University and their collaborators at Applied Biosystems say the microRNA expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets. MiR-125b is highly expressed in hematopoietic stem cells and overexpression in mouse HSC enhanced their function, the researchers write. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage, and "consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13," the team adds. This effect is associated with the development of lymphoproliferative disease.

The Scan

Genetic Tests Lead to Potential Prognostic Variants in Dutch Children With Dilated Cardiomyopathy

Researchers in Circulation: Genomic and Precision Medicine found that the presence of pathogenic or likely pathogenic variants was linked to increased risk of death and poorer outcomes in children with pediatric dilated cardiomyopathy.

Fragile X Syndrome Mutations Found With Comprehensive Testing Method

Researchers in Clinical Chemistry found fragile X syndrome expansions and other FMR1 mutations with ties to the intellectual disability condition using a long-range PCR and long-read sequencing approach.

Team Presents Strategy for Speedy Species Detection in Metagenomic Sequence Data

A computational approach presented in PLOS Computational Biology produced fewer false-positive species identifications in simulated and authentic metagenomic sequences.

Genetic Risk Factors for Hypertension Can Help Identify Those at Risk for Cardiovascular Disease

Genetically predicted high blood pressure risk is also associated with increased cardiovascular disease risk, a new JAMA Cardiology study says.