Research Roundup: May 4, 2018
Welcome to the May 4, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by researchers at the Broad Institute and their collaborators.
Evolutionary genetics revealed in the footsteps of Finnish migrations
Using a large repository of genetic data and birth-record data from Finland, an international team of researchers led by Broad institute member Mark Daly at Massachusetts General Hospital (MGH) and Alicia Martin has assembled one of the most comprehensive views of a population's recent evolutionary genetics to date. In a study published recently in the American Journal of Human Genetics, the authors combined Finnish population data with genetic variation data from 43,254 Finns, deriving high-resolution migration maps and evolutionary origins of rare-disease variants. Find out more in this Q&A with Martin in the Broadminded blog.
When headaches are a family affair
Migraine tends to run in families, but it’s not clear if this clustering is due to rare, highly penetrant variants in individual genes or common, less powerful ones spread across many genes. Broad associate member Aarno Palotie of MGH and the Institute for Molecular Medicine Finland, Padhraig Gormley, Mitja Kurki, and colleagues built a polygenic risk score using data from a migraine genome-wide association study, and used it to study the impacts of common and rare variation in a large cohort of families. Reporting in Neuron, they found higher risk scores among familial migraine cases, suggesting that common variants play a significant role in family clustering.
Dual data dives dig into cancers' distinctiveness
Tumors’ genetic landscapes can reveal potentially powerful patterns when linked to the right data. Case in point: two papers published this week by Broad institute member Gad Getz of MGH and colleagues. In Nature Communications, Getz, Nicholas Haradhvala, Jaegil Kim, Yosi Maruvka, Michael Lawrence, Dana-Farber Cancer Institute's Kent Muow, and collaborators used an assortment of computational tools (including the recently developed SignatureAnalyzer and MSMutect) to link simultaneous DNA proofreading and mismatch repair defects with distinct mutational signatures within cancer cells. And in Nature Medicine, Getz, Chip Stewart, and Andrew Dunford teamed up with Dana-Farber's Bjoern Chapuy and Margaret Shipp and others to reveal five discrete subtypes of diffuse large B cell lymphoma, using molecular and clinical data to connect genetics, mechanism, and outcome. Learn more in a Dana-Farber press release.
Autism data fuel a new view on noncoding variation
Studies of the noncoding genome for disease-associated variants present considerable analytical challenges, but a team led by Broad associate member Michael Talkowski at MGH, Harrison Brand, Matthew Stone, and colleagues has developed a new framework to address these barriers in whole-genome studies of common, complex diseases. The team analyzed 519 autism spectrum disorder (ASD) families from the Simons Simplex Collection using this framework, and were unable to demonstrate a rare noncoding variant contribution to ASD risk. The results, described in Nature Genetics, highlight the need for significantly larger sample sizes in studies of noncoding variation. Check out more in a related Nature News & Views piece.
CRISPR tools get a tune up
We’ve heard a lot about CRISPR this week in the news, and on the Broad website, we tell a tale of an ever-evolving field that’s not slowing down anytime soon. Read our feature story on the ways that the CRISPR toolbox is being optimized and expanded to give more precision and capabilities to an already powerful genome editing system, and for a glimpse of what is on researchers’ wish list for innovations to come.