Breakthrough: Scientists Create First Genetic Maps for Disease-Linked DNA Repeats

A team of researchers, led by the University of California, Irvine, has developed the initial genetic reference maps for short segments of DNA that repeat multiple times. These repetitions are known to be the cause of over 50 severe human diseases like amyotrophic lateral sclerosis, Huntington’s disease, and various cancers.

The UC Irvine Tandem Genome Aggregation Database has been established to allow researchers to investigate the links between these mutations, known as tandem repeat expansions, and diseases. This database aims to enhance our understanding of health inequalities and improve clinical diagnostics.

Published in the journal Cell, the study introduces the UC Irvine TR-gnomAD, bridging a critical gap in current genome sequencing efforts in biobanks. While TR expansions make up about 6% of our genome and significantly contribute to complex congenital conditions, our scientific comprehension of them remains limited.

This innovative initiative places UC Irvine at the forefront of human and medical genetics, addressing the vital need to interpret TR expansions in individuals with genetic disorders. The TR-gnomAD enhances our capacity to determine how specific diseases may impact diverse populations based on variations in these mutations among different ancestries. This information can aid genetic counseling services in developing products to interpret and accurately communicate how certain traits may be associated with various groups of individuals and diseases.”

Wei Li, the Grace B. Bell Chair and professor of bioinformatics and co-corresponding author

In constructing the database, the team employed two software tools to analyze genomic data from 338,963 participants across 11 sub-populations. Out of the .91 million TRs identified, .86 million were deemed of sufficient quality for further analysis. Interestingly, it was observed that 30.5% of these TRs exhibited at least two common alternative forms of a gene due to a mutation situated in the same chromosomal location.

“Although we have successfully genotyped a considerable number of TRs, this is only a fraction of the total present in the human genome,” Li commented. “Our next objectives involve prioritizing the inclusion of a larger set of high-quality TRs and encompassing more underrepresented ancestries like Australian, Pacific Islander, and Mongolian populations as we advance towards personalized precision medicine.”

Collaborating with UC Irvine were co-corresponding author and research assistant professor Ya Cui, postdoctoral scholar Wenbin Ye, biological chemistry graduate student Jason Sheng Li, and pediatrics professor and Institute for Clinical and Translational Science director, Eric Vilain. Additionally, participants included Jingi Jessica Le, a biostatistics professor at UCLA, and Dr. Tamer Sallam, vice chair and associate professor at the UCLA David Geffen School of Medicine.