Peter Salovey President | Yale University
Peter Salovey President | Yale University
A team of geneticists at Yale University has developed a new tool to identify disease-causing mutations in mitochondrial DNA (mtDNA). This development, led by Nicole Lake and Monkol Lek, provides a much-needed method for determining which mutations in the mitochondrial genome contribute to disease. The study was recently published in the journal Nature.
Nicole Lake, an assistant professor of genetics at Yale School of Medicine and the Yale Center of Genomic Health, stated, “We had few tools to help us identify disease-causing mutations in the mtDNA. While there are dozens available for the nuclear genome, this tool for the first time is providing a map of which sites in the mitochondrial genome are most important for health and disease.”
Mitochondria are cellular structures responsible for energy production and contain DNA inherited from one's mother. Attempts to build a constraint model for mitochondria have been challenging due to their small size and unique features. The Yale team overcame these challenges by developing a novel constraint model using a "composite likelihood" approach to analyze newly arising genetic mutations.
The research builds on previous work by Lake and Lek involving a data set of 56,434 individuals created with colleagues from the Broad Institute of MIT and Harvard. By applying their new model to this data set, they confirmed its effectiveness in identifying regions with mutations contributing to mitochondrial diseases.
“We built a mutational model that was really predictive and gave us the results we had hoped to see,” said Lake. To further validate their findings, they incorporated data from another large genomic project, the UK Biobank. Their constraint model remained robust when applied to this expanded pool.
Lek emphasized the importance of collaboration: “It’s about building a model that’s robust; that can be verified. That’s reliable and reliably predictive.” He credited Nicole Lake's initiative following discussions with Shamil Sunyaev from Harvard during early 2020.
Lake sees this breakthrough as just the beginning: “This is an important advance but there is exciting potential to expand,” she said. The tool will be freely accessible worldwide, offering significant promise for future research into mtDNA variations linked to diseases.
The international research team also included Kaiyue Ma, Kenneth K. Ng, Justin Cohen, and Hongyu Zhao from Yale School of Medicine.
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