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This Week in PLoS: Nov 29, 2009

In PLoS Biology this week, scientists led by Nicole Washington at Lawrence Berkeley National Laboratory and Melissa Haendel at the University of Oregon tested the hypothesis that "ontological annotation of disease phenotypes will facilitate the discovery of new genotype-phenotype relationships within and across species." Using a novel Entity-Quality methodology, they compared gene-linked disease phenotypes among model organisms, including zebrafish, and found that they could "identify, through the similarity of the recorded phenotypes, other alleles of the same gene, other members of a signaling pathway, and orthologous genes and pathway members across species" that could be involved in the disease.

"GWA studies to date have mostly focused on populations of rich countries, and there is a case for greater scientific investment in GWA studies relevant to the needs of developing countries," says an article in PLoS Medicine written by scientists from the University of Oxford, Wellcome Trust, the Kwame Nkrumah University of Science and Technology in Kumasi, Ghana, and the University of Bamako in Mali. They go on to articulate some of the ethical issues surrounding the problem of releasing data to the broader scientific community through describing the effort to develop a data release policy for the Malaria Genomic Epidemiology Network, or MalariaGEN.

A paper in PLoS Genetics this week shows that in Wilms' tumor, a childhood cancer of the kidney, long-range epigenetic silencing of protocadherins leads to tumor development and progression. The scientists, led by Keith Brown and Karim Malik at the University of Bristol, conducted a genome-wide analysis of promoter hypermethylation in the tumors and identified hypermethylation at chromosome 5q31 spanning more than 50 genes. All the genes belong to the α-, β-, and γ-protocadherin gene clusters. Expression analysis in mice and rat cells showed that over-expression inhibits cancer growth, pinpointing PCDHs as "candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling."

In PLoS One, researchers at the Swedish University of Agricultural Sciences in Uppsala, Sweden, studied global gene expression in uteri of female dogs with uterine bacterial infection. They found almost 800 genes to be significantly up-regulated, among those genes associated with proteolysis, and almost 700 genes down-regulated, "of which various homeobox and zinc finger transcription factors were highly represented." Several of these might have potential as biomarkers or therapeutic targets, for both dogs and humans, they say.

The Scan

Octopus Brain Complexity Linked to MicroRNA Expansions

Investigators saw microRNA gene expansions coinciding with complex brains when they analyzed certain cephalopod transcriptomes, as they report in Science Advances.

Study Tracks Outcomes in Children Born to Zika Virus-Infected Mothers

By following pregnancy outcomes for women with RT-PCR-confirmed Zika virus infections, researchers saw in Lancet Regional Health congenital abnormalities in roughly one-third of live-born children.

Team Presents Benchmark Study of RNA Classification Tools

With more than 135 transcriptomic datasets, researchers tested two dozen coding and non-coding RNA classification tools, establishing a set of potentially misclassified transcripts, as they report in Nucleic Acids Research.

Breast Cancer Risk Related to Pathogenic BRCA1 Mutation May Be Modified by Repeats

Several variable number tandem repeats appear to impact breast cancer risk and age at diagnosis in almost 350 individuals carrying a risky Ashkenazi Jewish BRCA1 founder mutation.