Rare mutations tracked, genetic landscapes explored, and a data translator envisioned.
Research Roundup: November 30, 2018
Welcome to the November 30, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Teasing apart the fabric of psychiatric genetics
Raymond Walters and institute member Benjamin Neale of the Stanley Center for Psychiatric Research, together with collaborators in the Psychiatric Genomics Consortium (PGC), published two large GWAS studies this week, one in Nature Neuroscience on alcohol dependence, the other in Nature Genetics on ADHD (with colleagues from Denmark's iPSYCH consortium). In addition to their distinct findings — such as unique alcohol dependence variants in European and African populations, and 12 genomic loci that impact ADHD risk — both studies called attention to significant genetic overlaps between these and a variety of other behavioral and psychiatric traits. Learn more about the alcohol study in a Washington University press release, and about the ADHD study in a Broad news story, an Aarhus University press release, and stories in GenomeWeb and The Guardian.
Tracking mutations, cell by cell
Identifying how mutations accumulate in a cell population over time is a critical element of understanding diseases such as age-related neurodegeneration and cancer. Yehuda Brody, core institute member Paul Blainey, and colleagues now report a new technique, called lineage sequencing, to understand this process. The approach enables scientists to overcome sequencing error to accurately reconstruct a timeline of rare somatic mutation events in a clonal cell population, with resolution down to the single-cell level. The researchers envision that lineage sequencing could be applied widely to study spontaneous and exposure- or therapy-associated mutational processes in remarkable detail. Learn more in Genome Research.
Laying out the genetics of a rare bone-marrow disease
Diamond-Blackfan anemia (DBA), an inherited rare disease, leads to bone-marrow failure and affects seven out of every million live births. Current therapy options including corticosteroid (hormone) therapy and stem cell transplant can cause other significant side effects. To characterize the genetic landscape of DBA and gain a better understanding of its treatment outcomes, a team led by Jacob Ulirsch, Jeffrey Verboon, and associate member Vijay Sankaran (all in the Program for Medical and Population Genetics) and collaborators performed whole-exome sequencing for a cohort of 472 individuals diagnosed with the disease. Reporting the detailed analysis in the American Journal of Human Genetics, researchers hope that the study will inform future clinical treatments of DBA and advance the understanding of other rare diseases.
A translational vision comes into focus
To better translate advances from basic to clinical to public health science, a consortium of scientists in 2016 committed to the vision of a Biomedical Data Translator, an effort to bridge symptom-based diagnosis with molecular and cellular characterizations through an informatics platform comprising diverse data types. In Clinical and Translational Science, consortium members describe early, encouraging results of the effort’s feasibility phase. Read more in an editorial, a paper summarizing the group’s work so far, and a second paper, penned by corresponding author and institute scientist Paul Clemons of the Chemical Biology and Therapeutic Science Program, describing the scientific community that has helped develop the prototype Translator system.