The University of California, Irvine research team has created the first genetic reference maps for short lengths of DNA repeated multiple times that are linked to over 50 fatal human diseases, such as ALS and Huntington’s disease. The UC Irvine Tandem Genome Aggregation Database allows researchers to investigate the connection between tandem repeat expansions and diseases, improve clinical diagnostics, and understand health disparities. This groundbreaking study, published in the journal Cell, introduces the UC Irvine TR-gnomAD, filling a critical gap in current genome sequencing efforts by focusing on tandem repeat expansions, which make up 6 percent of the human genome and significantly impact complex congenital conditions.
Wei Li, professor of bioinformatics, describes the project as positioning UC Irvine as a leader in human and medical genetics. By studying the diversity of tandem repeat expansions among different ancestries, the TR-gnomAD database helps genetic consulting companies develop products to accurately interpret this information and determine how certain diseases may affect specific groups of people. The research team used two software tools to analyze genomic data from over 330,000 participants across 11 sub-populations, identifying around 2.91 million TRs with 2.86 million considered of high quality. Additionally, they discovered that 30.5 percent of these TRs had at least two common alternative forms of a gene, indicating the complexity of these mutations.
Despite successfully genotyping a large number of TRs, the team acknowledges that this represents only a fraction of the total TRs in the human genome. Future steps include integrating a greater number of high-quality TRs, as well as including more underrepresented ancestries in the database, such as Australian, Pacific Islander, and Mongolian populations, to move towards personalized precision medicine. The research involved collaboration from various UC Irvine team members, including Ya Cui, Wenbin Ye, Jason Sheng Li, and Eric Vilain, as well as Jingi Jessica Le from UCLA and Dr. Tamer Sallam from the UCLA David Geffen School of Medicine.
The development of the UC Irvine TR-gnomAD database showcases the team’s commitment to advancing genetic research and improving clinical outcomes for individuals with genetic disorders. By filling a critical gap in understanding tandem repeat expansions, the database allows for more comprehensive studies on the genetic factors behind various diseases, including cancer. By including underrepresented ancestries and prioritizing the integration of high-quality TRs, the research team aims to provide a more inclusive and accurate platform for studying how diseases affect diverse populations. This project positions UC Irvine as a leader in the field of human and medical genetics, leading to advancements in personalized precision medicine.
The implications of this research extend beyond genetic diagnostics, offering a deeper understanding of health disparities and the genetic factors influencing certain diseases. By shedding light on the complexities of tandem repeat expansions and their role in genetic disorders, the UC Irvine TR-gnomAD database paves the way for more targeted and effective treatments for individuals with these conditions. As the team continues to expand the database and include more diverse populations, the potential for personalized precision medicine becomes even greater, offering hope for improved clinical outcomes and a more comprehensive understanding of genetic diseases on a global scale.
