The Encyclopedia of DNA Elements (ENCODE) collaboration was launched 17 years ago by the National Human Genome Research Institute with the goal of developing the tools and expertise needed to shed light on the 98% of our genome that does not code for proteins. Now in its final year, ENCODE has made huge advances thanks to the combined scientific and technological prowess of several hundred researchers at dozens of institutions. Leading the project for Berkeley Lab are Diane Dickel, Len Pennacchio, and Axel Visel, co-PIs of the Mammalian Functional Genomics Laboratory in Biosciences’ Environmental Genomics and Systems Biology (EGSB) Division. They are co-authors on 4 of the 15 new ENCODE papers published this week as part of a special collection in Nature.
Deciphering the Impact of Non-coding Mutations in the Human Genome
The Mammalian Functional Genomics Laboratory in Biosciences’ Environmental Genomics and Systems Biology (EGSB) Division has developed a higher-throughput transgenic mouse assay to evaluate the disease-causing potential of human variants in enhancers that turn on gene expression during development. The new approach leverages the CRISPR-Cas9 genome editing technology to create transgenic mice that carry an enhancer-reporter construct at a specific “safe harbor” location in the mouse genome. Because the transgenes are integrated in the same location in the genome there are no position effects, so fewer mice are needed to get reproducible results. To demonstrate proof of principle, the researchers used the new method—which they dubbed enSERT (enhancer inSERTion)—to examine nearly a thousand variants of one of the most well-characterized human enhancers that is associated with polydactyly (extra fingers or toes).
JGI Team Helps Uncover Sorghum’s Secrets for Drought Tolerance
Sorghum bicolor (L.) Moench is an African grass that adroitly handles droughts, floods and poor soils. While sorghum is drought-tolerant, the crop’s precise response is dependent on when exactly water becomes a limiting factor – before or after flowering. Reported in PNAS the week of December 2, 2019, is the first paper that describes sorghum’s response to drought, from a large-scale field experiment led by a multi-institutional consortium to uncover the mechanisms behind sorghum’s capacity to produce high yields despite drought conditions. Read the full highlight on the JGI website.
JGI Overhauls Perception of Inovirus Diversity
Inoviruses are filamentous viruses with small, single-stranded DNA genomes and a unique chronic infection cycle. In Nature Microbiology, a team led by DOE Joint Genome Institute (JGI) researchers applied machine learning to publicly available microbial genomes and metagenomes to search for inoviruses. The search tool combed through more than 70,000 microbial and metagenome datasets, ultimately identifying more than 10,000 inovirus-like sequences compared to the 56 previously known inovirus genomes. The results revealed inoviruses are in every major microbial habitat—including soil, water, and humans—around the world.
“We’re not sure why we systematically manage to miss them; maybe it’s due to the way we currently isolate and extract viruses,” said the study’s lead author Simon Roux, a JGI research scientist in the Environmental Genomics group. Click here to read the full story on the JGI site.
Epic Research Endeavor Reveals Cause of Deadly Digestive Disease in Children
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.
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