Researchers at the University of California, Irvine have created genetic reference maps for short sections of DNA that are repeated numerous times. These repetitive DNA sequences are linked to over 50 deadly human diseases, such as amyotrophic lateral sclerosis, Huntington’s disease, and various types of cancer. The project, known as the UC Irvine Tandem Genome Aggregation Database, is the first of its kind to provide this comprehensive genetic information.The UC Irvine TR-gnomAD database allows researchers to investigate the link between tandem repeat expansions and diseases, health disparities, and clinical diagnostics. This study, featured in the journal Cell, introduces the UC Irvine TR-gnomAD, which fills a crucial gap in current biobank genome sequencing efforts. Despite TR expansions making up about 6% of our genome and playing a significant role in complex congenital conditions, our scientific understanding of them is still limited. This project positions UC Irvine at the forefront of human and medical genomics.”TR-gnomAD is an important advancement in genetics because it helps us understand TR expansions in individuals with genetic disorders,” explained Wei Li, the Grace B. Bell Chair and professor of bioinformatics and co-corresponding author. “This database enhances our ability to assess the impact of certain diseases on diverse populations by analyzing variations in these mutations among ancestries. With this information, genetic consulting companies can create products to accurately report how specific traits may be linked to different groups of people and diseases.”
The team used two software tools to analyze and build the database.The study examined genomic data from 338,963 participants in 11 different sub-populations. Out of the 0.91 million TRs that were identified, 0.86 million were deemed to be of high quality and suitable for further analysis. It was also found that 30.5 percent of these TRs had at least two common alternative forms of a gene due to a mutation at the same location on a chromosome.
“While we have successfully genotyped a significant number of TRs, this is only a small fraction of the total number in the human genome,” Li explained. “Our next steps will involve prioritizing the integration of a larger number of high-quality TRs and including more underrepresented ancestries, such as those from Australia.The research involved members of the UC Irvine team such as co-corresponding author Ya Cui, research assistant professor; Wenbin Ye, postdoctoral scholar; Jason Sheng Li, graduate student in biological chemistry; and Eric Vilain, professor of pediatrics and director of the Institute for Clinical and Translational Science. Also involved were Jingi Jessica Le, professor of biostatistics at UCLA, and Dr. Tamer Sallam, vice chair and associate professor at the UCLA David Geffen School of Medicine. This research brings us closer to achieving personalized precision medicine for diverse populations, including individuals of African, Pacific Islander and Mongolian descent.Â
