An international team led by investigators in Germany and the US describe the transcription factor binding-based scheme they established for evaluating loci linked to type 2 diabetes risk. In their Cell study, the researchers demonstrated that this integrative computational strategy — which takes into account transcription factor binding site phylogeny and conservation in multiple species — can track down type 2 diabetes-associated variants with mechanistic ties to the disease. "[C]ross-species conservation analysis at the level of co-occurring [transcription factor binding sites] provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms," the study's authors say.
The Sloan-Kettering Institute's Zhirong Bao and colleagues present a systems biology-based method for using cellular imaging and targeted gene deletion to delve into the mechanistic events involved with cell differentiation. With the help of tissue-specific markers for gauging phenotypes, the researchers used their model to track differentiation in hundreds of Caenorhabditis elegans embryos lacking one of 20 different genes. "The result not only recapitulates current knowledge but also provides insights into gene function and regulated fate choice," they write, "including an unexpected self-renewal."
Finally, a team from the UK and Germany looks at the imprinted loci architecture in mice, focusing on 97 physical traits. Through a series of crosses, array-based gene expression experiments, and gene knockout studies involving heterogeneous mouse stocks, the researchers saw heritability in parent-of-origin expression effects. They also detected signs of parent-of-origin effects involving non-imprinted loci that appear to result from interactions with loci that are imprinted. "We propose that this gene network effect may account for some of the missing heritability seen when comparing sibling-based to population based studies of the phenotypic effects of genetic variants," the study's authors argue.