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This Week in PLoS: Mar 23, 2009

Scientists at the University of Edinburgh have found that the DISC1 gene affects how patients with schizophrenia respond to treatment. Their work was published in PLoS One this week. Looking across public datasets, they found correlations between variants in the DISC1 pathway genes and levels of gene expression, and that variants of DISC1, NDE1, PDE4B, and PDE4D regulate the expression of cytoskeletal, synaptogenic, neurodevelopmental, and sensory perception proteins. "We know that disorders such as schizophrenia have a genetic element and that this specific gene, DISC1, is important to that process," lead author William Hennah says in a BBC story.

Also in PLoS One this week, researchers have performed genome-wide methylation analysis in head and neck squamous cell carcinoma, a cancer causally associated with human papillomavirus. Using pyrosequencing, they looked at hypomethylation levels in 26 HNSCC samples for LINE repeats and found that LINE and Alu hypomethylation was different among different cancer cell lines. LINE hypomethylation was more pronounced in HPV-negative than in HPV-positive tumors, and genomic instability was greater in HNSCC samples with more pronounced LINE hypomethylation.

Berkeley scientists have written an algorithm to accurately detect recombinant breakpoints in whole-genome alignments. Using a combined algorithm for estimating tree structure and hidden Markov model parameters, they tested their method on datasets from two recombinant pathogens, Neisseria and HIV-1, showing that they could not only "detect recombinant regions of vastly different sizes but also the location of breakpoints with great accuracy." They published in PLoS Computational Biology this week.

In PLoS Genetics, a GWAS confirmed three variants -- VKORC1, CYP2C9, and CYP4F2 -- as the major genetic variants in determining warfarin dose for Caucasians, who vary widely in their ability to metabolize the drug. Led by scientists at the Wellcome Trust Sanger Institute, this is the first genome-wide association study "whose sample size is sufficiently powered to detect genome-wide significance for polymorphisms that modestly alter therapeutic warfarin dose," the scientists wrote in the abstract. They looked at 1,053 Swedish test subjects and confirmed their findings in 588 additional Swedish patients.