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Genomics In The Journals: Apr 5, 2012

NEW YORK (GenomeWeb News) – Researchers from Johns Hopkins University used comparative array-based gene expression analyses to look at response to dengue virus infection in female Aedes aegypti mosquitoes, a key vector for dengue virus transmission.

As they report in PLoS Pathogens, the team saw differential expression for almost 150 genes in the salivary glands of A. aegypti when they compared mosquitoes with or without dengue virus infection. These included genes involved in everything from viral replication and mosquito immune response to feeding and odor reception. Based on these results, combined with follow-up experiments using RNA interference to silence specific mosquito genes, the study suggests some of the infection-related expression changes actually enhance A. aegypti's feeding ability to find and feed on hosts, perhaps spreading the virus as it does so.

"The virus may … facilitate the mosquito's host-seeking ability, and could — at least theoretically — increase transmission efficiency, although we don't fully understand the relationships between feeding efficiency and virus transmission," Johns Hopkins University molecular microbiology and immunology researcher George Dimopoulus, the study's senior author, said in a statement.

A study involving a hypothesis-driven genome-wide association study implicated cell membrane component coding genes in susceptibility to an intestinal blockage condition called meconium ileus, which develops in a subset of individuals with cystic fibrosis.

As they report in Nature Genetics, researchers from Canada, France, and the US did a GWAS involving 611 cystic fibrosis patients with, and 3,152 cystic fibrosis patients without, meconium ileus that was replicated in almost 2,400 more individuals. The team also did a hypothesis-driven GWAS approach using information on the cystic fibrosis disease process to prioritize the candidate SNPs. Among the apparent cystic fibrosis modifier variants identified were SNPs in and around the transporter genes SLC6A14, SLC26A9, and SLC9A3, suggesting cell membrane components besides the CFTR gene that causes cystic fibrosis can affect disease symptoms and severity.

The study "provides molecular insight into the role of genetic variation in ion transporters in CF, which may be applicable to more commonly, and severely, involved organs such as the lungs," senior author Michael Knowles, a researcher with the University of North Carolina's Cystic Fibrosis-Pulmonary Research and Treatment Center, said in a statement. Clarifying the pathogenic processes behind meconium ileus "offers the possibility of developing therapies to intervene in utero," he noted.

In the Proceedings of the National Academy of Sciences, a Massachusetts research team describes its strategy for identifying a range of bacterial, viral, yeast, and parasite pathogens in clinical samples using targeted RNA transcript profiling.

In their initial experiments, researchers came up with probes to quantify species-specific transcripts from Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae using NanoString Technologies' nCounter analysis based on publicly available sequence data for the bugs. They then showed that the same approach could accurately identify several other bacterial species, as well as fungi and viruses, including influenza, herpes simplex virus-2, and HIV-1.

The group's other experiments illustrate that the same strategy could also be useful for distinguishing drug-sensitive from -resistant pathogens using information on RNA transcripts expressed in response to drug treatments.

"The current wealth of genomic and transcriptomic data available should promote the development of substantially improved diagnostics for infectious diseases," senior author Deborah Hung, a researcher affiliated with the Broad Institute, Massachusetts General Hospital, and Brigham and Women's Hospital, and colleagues wrote. "Our work suggests that an RNA-based diagnostic can capitalize on this information by taking advantage of both static genome sequences and dynamic transcriptional responses."

By generating a high-quality reference genome assembly for a freshwater threespine stickleback fish from Alaska and using this genome as the basis for a more extensive comparison involving 20 more threespine sticklebacks from marine and freshwater populations around the world, an international team has found clues to the genetic changes that have accompanied adaptation to these distinct environments — work that appears in Nature.

While alterations to protein-coding genes or regulatory sequences from at least 147 regions in the genome appear to have contributed to divergence between marine and freshwater stickleback, for instance, the researchers found that regulatory changes were more common overall than gene coding shifts.

"The fact that regulatory changes appear to predominate in adaptive evolution makes sense," co-corresponding author Kerstin Lindblad-Toh, a researcher affiliated with the Broad Institute and Uppsala University, said in a statement. "If a protein was completely changed, it would probably have a different function in many different cell types — and that could be detrimental to the fish rather than help it adapt to a new environment."

In 2010, another research group published a study in PLoS Genetics looking at parallel evolution in threespine sticklebacks from three Alaskan lakes and two ocean sampling sites based on restriction-site associated sequence tag-based genotyping and comparisons against a draft version of the stickleback genome.

Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.