Berkeley Lab geneticist Len Pennacchio and his team helped a group of Israeli clinical researchers solve the mystery of a rare inherited disease that causes extreme, sometimes fatal, chronic diarrhea in children. The nearly decade-long investigation not only led to the discovery of a novel protein-coding gene that is critical for intestinal function, but also expanded our understanding of regulatory sequences in the human genome. The results were recently published in Nature.
Gene Enhancers Are Important Despite Apparent Redundancy
Though once thought to be “junk DNA,” enhancers are extremely important, regulating the expression of specific genes that ultimately determine a cell’s properties and functions. However, there are many more enhancers than genes and their relationship is unclear. A team of scientists in the Environmental Genomics & Systems Biology Division have turned their attention to this relationship and the overall importance of enhancers to development. By better linking the genomic complement of an organism with its expressed characteristics, their work offers new insights that further the growing field of systems biology, which seeks to gain a predictive understanding of living systems.
JGI Maps Bacterial Genes That Regulate Microbe-Plant Root Interactions
A plant’s health and development is influenced by the complex community of microbes that surrounds it. Researchers at the Joint Genome Institute (JGI) and their collaborators at the Howard Hughes Medical Institute at the University of North Carolina have identified some 350 genes of the bacterium Pseudomonas simiae that positively or negatively impact how effectively this beneficial microbe colonizes plant roots. Cataloging these genes—and understanding the cellular functions that they’re involved in—is the first step toward developing targeted approaches to improving plant health and growth for a number of applications. The results of the study were published in PLOS Biology. Read more on the JGI website..
Modular Ensembles of Enhancers Regulate Ihh, Developmental Gene Expression in Mice
Biosciences researchers Axel Visel (JGI/EGSB) and Marco Osterwalder (EGSB) contributed to a study, led by researchers at the Max Planck Institute for Molecular Genetics, in which targeted genome editing and a transgenic reporter assay were used to characterize elements regulating Ihh (encoding Indian hedgehog) in mice. Indian hedgehog is a mammalian signaling protein involved with the development and proliferation of cells in cartilage. In humans, copy number variants (CNVs) upstream of Ihh cause localized phenotypes including premature fusion of the sutures of the skull and malformation of the phalanges. The study, published in Nature Genetics, showed that in mice Ihh is regulated by modular ensembles of enhancers (with individual tissue specificities) that appear to act in an additive manner. Despite apparent redundancy and overlapping function of enhancers, these ensembles—in which the correct number of each enhancer is present—are necessary for precise spatiotemporal control of developmental gene expression.
Researchers Collaborate to Create, Characterize Mouse Model of Autism
Using a genetic mouse model developed at Berkeley Lab with CRISPR/Cas9 editing technology, University of California, Davis, researchers led by Alexander Nord have examined the developmental impact of a specific mutation found in some rare cases of autism spectrum disorder (ASD). The project began while Nord—now an assistant professor with the Center for Neuroscience at UC Davis—was a postdoc in the Mammalian Functional Genomics Laboratory of Berkeley Lab co-authors Axel Visel, Len Pennacchio, and Diane Dickel. In a paper published June 26 in the journal Nature Neuroscience, the researchers report that mice with a loss-of-function mutation in one copy of the CHD8 gene have increased brain volume and cognitive impairment, similar to that seen in people with the same mutation. CHD8 encodes a protein responsible for packaging DNA in cells, which in turn controls gene expression during development. Read more from UC Davis.
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