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Genomics In The Journals: Aug 23, 2012

NEW YORK (GenomeWeb News) – Members of the Genetic Investigation of Anthropometric Traits consortium and investigators from a handful of research centers in Massachusetts have identified subtle signs of selection affecting multiple genetic variants associated with height in the European population.

As they report in Nature Genetics, the researchers found that the frequency of alleles believed to promote height were more common in individuals of northern European ancestry, who tend to be relatively tall, than in typically shorter populations from southern parts of the continent. As such, they say, the work offers an example of a phenomenon dubbed polygenic adaptation — weak selection simultaneously affecting many sites in the genome. This pattern held both at loci that have been significantly associated with height in Europeans and at alleles with more tenuous ties to the trait.

"By aggregating evidence of directionally consistent intra-European frequency differences over many individual height-increasing alleles, none of which has a clear signal of selection on its own, we observed a combined signature of widespread weak selection," senior author Joel Hirschhorn, a researcher affiliated with the Broad Institute, the Children's Hospital Boston, and Harvard Medical School, and colleagues noted.

"However," they added, "we were not able to determine whether this differential weak selection (either positive or negative) favored increased height in northern Europe, decreased height in southern Europe, or both."

In Nature Chemical Biology, a University of California at Riverside team outlines the method that it developed for detecting glitches in transcription stemming from underlying DNA damage.

The so-called competitive transcription and adduct bypass, or CTAB, assay relies on the use of non-replicating plasmid DNA that contains a specific DNA lesion. Using mass spectrometery, the researchers followed the transcriptional consequences of these DNA trouble spots, modeling the types of damage that can stem from exposure to an outside agent or processes inside the cell itself. In their own study, for instance, the researchers saw a dip in transcription in mammalian cells following the introduction of various types of oxidative DNA damage. And down the road, they say, the CTAB approach is expected to prove useful for exploring the interplay between other DNA modifications, the transcriptional system, and DNA repair proteins.

In the early, online edition of Proceedings of the National Academy of Sciences, a study provides a look at the genetic consequences of extensive and ongoing inbreeding in a population of butterflies living on an island in the Baltic Sea.

Finnish researchers assessed seven microsatellite markers — along with dozens of physical and behavioral traits — in a population of Glanville fritillary butterflies that's been isolated for at least 75 years, comparing them with butterflies of the same species from a much larger population from Estonia. Based on analyses of both traits and genetic profile, the team concluded that the isolated butterflies are experiencing decreased genetic diversity and an accumulation of potentially damaging recessive mutations that are on their way to becoming fixed in the population through a process known as genetic load.

"This population exemplifies the increasingly common situation in fragmented landscapes, in which small and completely isolated populations are vulnerable to extinction due to high genetic load," senior author Ilkka Hanski, a biosciences researcher at the University of Helsinki, and colleagues wrote.

Low doses of antibiotics could potentially contribute to obesity by altering the gut microbial community and its metabolic capabilities, according to a new study in mice.

As it reports in Nature, a New York University-led team treated newly weaned mice with sub-therapeutic doses of three antibiotics, alone or in combination. Within around six weeks, researchers found that mice in the treatment group were heavier — boasting 10 to 15 percent more body fat than untreated mice. The antibiotic-treated mice also showed enhanced bone mineral density and elevated levels of at least one growth-related hormone involved. Such shifts coincided with changes to the composition and metabolic capabilities of the gut microbiome, the team found.

"This work shows the importance of the early life microbiome in conditions like obesity," NYU's Martin Blaser, the study's corresponding author, said in a statement, adding, "We're still learning how far the impact of the microbiome reaches and the costs of perturbing it."

The distinct methylation patterns present in the chimpanzee genome compared to the human genome may help to explain some differences in disease risk in the closely related primate species, according to an American Journal of Human Genetics study by researchers at the Georgia Institute of Technology and elsewhere.

The group focused on human-chimpanzee differences in DNA methylation in samples from the prefrontal cortex, a brain region tissue involved in complex and abstract thinking. Their methyl-C-seq experiments on post-mortem prefrontal cortex samples from three humans and three chimpanzees uncovered variability in DNA methylation between individuals and between species. Moreover, many of the intra-species methylation differences fell in stretches of sequence showing distinct gene expression patterns in human and chimpanzee brains. Among the differentially methylated promoters, researchers saw an over-representation of sequences near neurodevelopmental or psychological disease genes, which tended to show lower methylation levels and higher expression compared to their chimpanzee counterparts.

"Our results hint, but by no means provide proof, that epigenetic divergence — or changes of chemical properties of DNA — may be particularly important for some disease-related phenotypes that are pertinent to modern humans," Georgia Institute of Technology researcher Soojin Yi, the study's senior author, said in a statement.

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

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