African genomics study may aid understanding of disease susceptibility

The recently completed genomic mapping of populations in sub-Saharan Africa is already providing information about population expansion and movement among ethnic subgroups. For instance, the study found evidence of reintroduction of Europeans or Middle Easterners into Africa around 9,000 years ago. But understanding population movements was not the primary objective of the study, published in Nature in December 2014. The research team, headquartered at the Wellcome Trust Sanger Institute, Hinxton, UK, explored how to determine how genetic variation correlates with susceptibility to a variety of diseases and infectious agents. Researchers from the African Genome Variation Project collected genetic information from more than 1,800 people, including 320 whole-genome sequences from seven populations in sub-Saharan Africa. Doctors and researchers in Ethiopia, The Gambia, Ghana, Kenya, Nigeria, South Africa, and Uganda participated. After analyzing the data, they pinpointed 30 million genetic variants, including many that had not previously been identified. Several loci appeared to be associated with infectious disease susceptibility and severity. For example, the study flagged not only the well-known sickle cell locus related to malaria but new signals for genes potentially under selection in malaria endemic regions. Genes associated with Lassa fever included the already known LARGE gene as well as new candidates associated with viral entry and immune response. The results also suggest that existing reference panels are inadequately representing some African populations. The authors note that current and planned deep sequencing across an even broader swath of populations in Africa will soon provide a comprehensive resource for medical genomic studies in Africa. —Karyn Hede, News Editor

Niemann–Pick type C gene may hold key to treating Ebola

An exceedingly rare genetic defect is providing insight into what may be one of the most dreaded infectious diseases: the Ebola virus. It turns out that the virus latches onto the protein that is nonfunctional in patients with Niemann–Pick type C, a neurodegenerative condition affecting about 500 people worldwide. The Niemann–Pick CI (NPC1) protein is involved in transporting cholesterol within cells. But it is also a target that helps Ebola and HIV enter human cells. Without a functional copy of this protein, patients suffering from the deadly Niemann–Pick type C are, ironically, immune to Ebola and HIV. With the recent Ebola outbreak, more attention has been focused on related research, including the work of Kartik Chandran, of Albert Einstein College of Medicine, Bronx, NY. To better understand how the virus behaves when NPC1 is missing, Chandran is collaborating with families such as the Hempels, of Reno, Nevada, who have twin daughters born with the disease. Chandran and his colleagues have tried without success to infect the girls’ cells with Ebola. Studies in mice with only one functioning copy of the gene indicate that heterozygosity may also offer some protection from dying of the disease. In a CBS news report, Chandran speculated that a drug that blocks the virus from binding to the protein may be useful in treating Ebola. The research team is seeking a small-molecule drug that would block the NPC1 gene temporarily, just long enough to halt the virus in its tracks. —Karyn Hede, News Editor

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