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Genomics In The Journals: Nov 1, 2012

NEW YORK (GenomeWeb News) – An international team led by investigators at the Wellcome Trust Sanger Institute and Yale University did a meta-analysis on data from more than 75,000 cases and controls to track down 71 new genetic loci linked to inflammatory bowel disease.

Results of the study suggest that regions associated with Crohn's disease largely overlap with those showing ties to ulcerative colitis. And both conditions appear to have genetic overlap with immune-related conditions, the team noted. By looking at the sorts of genes present in all 163 sites in the genome that have been associated with IBD through this and previous analyses, those involved in the study also gained insights into the influence that bacteria may have had on IBD genetics. In particular, their results suggest that IBD involves inflammation and excessive host immune system response to mycobacterial infections. That notion was supported by the group's follow-up experiments, including expression studies in more than 200 mouse-derived immune cell lines that focused on genes from IBD-linked loci. The study appears in Nature.

"We see a genetic balancing act between defending against bacterial infection and attacking the body's own cells," the Wellcome Trust Sanger Institute's Jeffrey Barrett, the study's co-senior author on the study, said in a statement.

"Many of the regions we found are involved in sending out signals and responses to defend against bad bacteria," he explained. "If these responses are over-activated, we found it can contribute to the inflammation that leads to IBD."

Researchers from the US, UK, Canada, and Australia have used phylogenetic data to take a gander at bird diversity for another study slated to appear in Nature this week.

The team looked at bird biodiversity patterns over both evolutionary history and geographic space, using a newly developed phylogenetic tree that represents nearly 10,000 living bird species. From this phylogeny, for instance, researchers determined that there has been a jump in bird diversification within the past 50 million years or so, particularly in relatively young bird lineages such as those containing songbird species. Their results also point to diversification differences related to northern and southern hemisphere locales.

They noted that species peppered across the bird phylogenetic tree — and from a range of geographic regions — seem to have had high diversification rates over the course of bird history.

"The contribution of rapidly radiating lineages to both temporal diversification dynamics and spatial distributions of species diversity illustrates the benefits of an inclusive geographical and taxonomical perspective," the study's authors explained.

A study in mBio suggests that gut microbe communities in American honeybees contain more — and more diverse — antibiotic resistance genes than gut microbiomes from bees in other parts of the world.

The study's authors attributed this pattern to the use of a tetracycline-related antibiotic called oxytetracycline in US beekeeping. In that setting, they explained, the drug is often used to ward off foulbrood, a larval disease caused by bacterial pathogens.

The Yale University researchers used PCR- and sequencing-based assays to screen for antibiotic resistance genes in honeybees from several sites in the US. The search uncovered eight tetracycline resistance loci in the guts of honeybees from the US compared to three resistance loci in the gut microbiomes of bees from places where antibiotics are not used in beekeeping such as Switzerland, the Czech Republic, and New Zealand.

"It seems likely this reflects a history of using oxytetracycline since the 1950s," Yale ecology and evolutionary biology researcher Nancy Moran, the study's senior author, said in a statement, adding that this pattern "parallels findings in other domestic animals, like chickens and pigs."

In a study in the early, online version of Science, a research team from Sweden and Finland delved into the functional consequences of altering a MYC gene regulatory region that contains variants implicated in cancer risk in humans.

The investigators carried out their experiments in mice missing a stretch of regulatory element sequence upstream of MYC that is home to a conserved SNP called rs6983267. In human GWASs, that commonly occurring chromosome 8 variant is believed to contribute to colorectal and prostate cancer tumorigenesis, prompting interest in untangling its function.

Under normal circumstances, the researchers reported, mice that did not have the rs6983267-containing sequence showed similar, if slightly reduced, MYC expression compared to wild type mice. But under conditions that normally cause intestinal tumors in mice, the animals lacking rs6983267 were no longer susceptible to cancer, the study authors explained, consistent with an authentic, cancer-related role for the SNP.

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

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