A groundbreaking research team led by the University of California, Irvine has developed the first genetic reference maps for short DNA repeats linked to over 50 fatal human diseases, such as amyotrophic lateral sclerosis, Huntington’s disease, and various cancers. The newly established UC Irvine Tandem Genome Aggregation Database provides a platform for researchers to explore the connection between these mutations, known as tandem repeat expansions, and diseases, ultimately enhancing clinical diagnostics and understanding health disparities.

Published in the journal Cell, the study introduces the UC Irvine TR-gnomAD, addressing a crucial gap in current biobank genome sequencing efforts. Despite constituting approximately 6 percent of our genome and significantly contributing to complex congenital conditions, scientific comprehension of tandem repeat expansions remains limited.

Wei Li, the Grace B. Bell Chair and professor of bioinformatics at UC Irvine, emphasized the significance of the project in positioning the university as a leader in human and medical genetics. He highlighted the database’s potential to determine how certain diseases might impact diverse groups based on variations in these mutations among ancestries, enabling genetic consulting companies to develop products for accurate interpretation and reporting of the link between traits, different population groups, and diseases.

The research team employed two software tools to analyze the genomic data of 338,963 participants across 11 sub-populations, identifying 0.91 million tandem repeats. Of these, 0.86 million were of high enough quality for further study, revealing that 30.5 percent of them had at least two common alternative forms of a gene caused by a mutation located in the same place on a chromosome.

Li emphasized that while a substantial number of tandem repeats were successfully genotyped, this represents only a fraction of the total number in the human genome. The next steps for the team involve prioritizing the identification and characterization of tandem repeats, paving the way for enhanced understanding of their role in diseases and potential targeted therapeutic interventions.