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This Week in PNAS: Dec 22, 2015

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.

In a study slated to appear online this week in the Proceedings of the National Academy of Sciences, researchers from the US and Spain describe deleterious variants that have made their way into the dog genome during the process of domestication and accompanying artificial selection for particular breed traits. By scrutinizing new and existing genome sequences for 46 dogs from domestic breeds, 25 village dogs, 19 gray wolves, and one golden jackal, the team saw signs of diminished natural selection in the domestic dogs compared to wolves, likely reflecting domestication and breed formation-related bottlenecks. "Our findings question the overly typological practice of breeding individuals that best fit breed standards, a Victorian legacy," the authors argue. "This practice does not allow selection to remove potentially deleterious variation associated with genes responsible for breed-specific traits."

A Stanford University team considers the performance and limitations of the genome-wide complex trait analysis, or GCTA, method for tackling the problem of missing heritability in genome-wide association studies. When they applied the GCTA approach to SNP data for almost 2,700 unrelated individuals from the Framingham study, the researchers found that the approach produces heritability estimates that may be unreliable or unstable, depending on the type of data available. In particular, their results suggest that "the heritability estimates [GCTA] produces are highly sensitive to the structure of the genetic relatedness matrix, to the sampling of phenotypes and subjects, and to the accuracy of phenotype measurements."

Finally, American and Canadian researchers report on findings from a study of brain gene expression study that tracked circadian rhythms in the prefrontal cortex of the human brain, using post-mortem samples from 146 individuals. By folding in information on individuals' age and their time of death, the team was able to uncover genes showing circadian expression cycles in two parts of the brain called Brodmann's area 11 and Brodmann's area 47. Results from the analysis reveal age-related shifts in the genes showing rhythmic gene expression in these regions, including transcripts that appeared to lose their circadian cycles and others that began showing rhythmic expression in older individuals. GenomeWeb has more on the study, here.