Gene-Disrupting Variants in 141,456 Humans: Lessons for Biology and Drug Target Discovery.

12.30 – 1.30pmFRIDAY 15 FEBRUARY  |  Seminar Room, Education Centre


Presenter: Prof Daniel MacArthur

Chair: A/Prof Mike Innouye

Daniel MacArthur is an institute member at the Broad Institute of MIT and Harvard, and co-director of the Broad’s Program in Medical and Population Genetics. In addition to his roles at the Broad, MacArthur is a group leader in the Analytic and Translational Genetics Unit at Massachusetts General Hospital and an assistant professor at Harvard Medical School. His work revolves around the use of large-scale genomic data to interpret genetic variants, particularly in the context of rare, severe genetic diseases.

MacArthur’s team has assembled the largest collection of sequences of the protein-coding region (exome) of the human genome, creating a resource called the Genome Aggregation Database (gnomAD). This collection currently contains DNA sequencing data from over 140,000 individuals, and is made publicly available for anyone to use. As a result it has become the default reference database for clinical genetics labs, and is accessed over 15,000 times every day. It also serves as the basis for the Human Knockout Project, an ambitious global endeavour seeking to characterize the clinical impact of the disruption of each of the 20,000 genes in the human genome.

In addition, MacArthur leads a number of efforts applying genomic technologies to the diagnosis of very rare genetic diseases. He co-leads the Broad’s Centre for Mendelian Genomics, which uses both DNA and RNA sequencing technologies to investigate the genetic basis of rare diseases in thousands of families every year. In the first three years of the Centre’s operation it has been able to return genetic diagnoses to over 1,200 families – many of whom had been waiting many years for an answer using standard clinical testing – and identified nearly 100 likely new genes associated with a wide variety of diseases.

MacArthur was recognized for his work with the Harvard Medical School’s Young Mentor Award in 2016, the Massachusetts General Hospital Martin Prize in 2017, and was also the first ever recipient of the American Society of Human Genetics Early-Career Award in 2017.