In Nature this week, work led by Duke's David Goldstein used a GWAS to show that a SNP (rs12979860) three kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-lambda3, strongly associates with more than a two-fold difference in response to hepatitis C virus drug treatment in both European-Americans and African-Americans. In this week's early online edition, scientists led in part by Goldstein and NCI's Mary Carrington performed a follow-up genotyping experiment on HCV patients who either cleared or didn't clear the infection, and showed that "the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry." A perspective has more.
Novartis' Taiping Chen was lead author on a paper looking at how epigenetic marks affect gene imprinting in mice. "The authors find that methyl marks on histones need to be removed for the genome to 'get ready' for the establishment of imprints," says a perspective. Using a combination of cell-based assays and experiments in recombinant mice, they show that amine oxidase (flavin-containing) domain 1, a protein related to the lysine demethylase KDM1, serves as a histone H3 lysine 4 demethylase and is needed for de novo DNA methylation of some imprinted genes in oocytes.
In a study appearing this week in Nature Biotechnology, Hua Yu at the Beckman Research Institute at City of Hope was lead author on work that improves upon siRNA delivery into specific cells. Using an siRNA linked to a CpG oligonucleotide agonist of toll-like receptor 9 and targeted to the immune suppressor gene Stat3, they injected this into mice locally or intravenously and saw that it went into tumor-associated dendritic cells, macrophages, and B cells. When Stat3 was silenced, this activated "tumor-associated immune cells and ultimately to potent antitumor immune responses," they say in the abstract.
Another study used high-throughput chemical genomics to pinpoint new antimalarial drug targets. NIH's Xin-zhuan Su was senior author on work that screened seven Plasmodium falciparum parasite lines for differences in responses to 1,279 bioactive chemicals. They found 607 different "chemical phenoyptes" and hundreds of active compounds, including dihydroergotamine methanesulfonate (1), a serotonin receptor antagonist, which is encoded by a gene homolog of human P-glycoprotein.