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This Week in PNAS: Apr 9, 2013

By sequencing and comparing tumor and matched normal genome sequences from two sets of identical twins with acute lymphoblastic leukemia, a team from the UK, Italy, and the US was able to identify tumor-associated somatic mutations and track the timing with which they developed. As they reported in the early, online edition of the Proceedings of the National Academy of Sciences, the researchers found that the identical twins tended to share prenatal alterations that seem to spur ALL development. But in each twin pairs, the majority of suspicious mutations differed from one twin to the next, consistent with the notion that most of the genetic changes in tumors were secondary (or in some cases, passenger) mutations acquired in each individual after birth.

Wild gorillas and chimpanzees carrying parasites related to the malaria-causing pest Plasmodium falciparum do not seem to be an ongoing source of human infections, according to another PNAS study. An international team led by investigators at the University of Pennsylvania did targeted mitochondrial gene sequencing on blood samples from hundreds of malaria-infected individuals in Cameroon, looking for genetic signs of Plasmodium species or parasites from a P. falciparum-related Laverania sub-species that's known to be found in apes. The ape-associated Laverania species were not detected in human infections, researchers explain, and their phylogenetic analysis of P. falciparum parasites was consistent with a single historical transmission of this species from gorillas into humans.

Finally, Yale School of Meidicine's Daniel DiMaio and colleagues describe the genome-wide, small interfering RNA strategy they used to find factors in human cells that participate in human papillomavirus infection. Using a library of more than 18,000 siRNAs, the researchers screened for factors altering HPV pseudovirion entry into HeLa cells. The search unearthed several proteins, including so-called retromer sub-units — proteins participating in retrograde transport in the cell.

"These results provide important insights into HPV entry, identify numerous potential antiviral targets, and suggest that the role of the retromer in infection by other viruses should be assessed," DiMaio and co-authors note.