A research team led by the University of California, Irvine has built genetic reference maps for short lengths of DNA repeated multiple times, known as tandem repeat expansions. These mutations are linked to more than 50 lethal human diseases, including amyotrophic lateral sclerosis, Huntington's disease, and multiple cancers.
The UC Irvine Tandem Genome Aggregation Database (TR-gnomAD) enables researchers to study the connection between these mutations and diseases, helping to understand health disparities and improve clinical diagnostics. The study, published in Cell, addresses a critical gap in current biobank genome sequencing efforts, as tandem repeat expansions constitute about 6% of the human genome and substantially contribute to complex congenital conditions.
The team utilized two software tools to analyze the genomic data of 338,963 participants across 11 sub-populations. Of the 1.91 million TRs identified, 1.86 million were of high enough quality to be retained for further study. Notably, 30.5% of the TRs had at least two common alternative forms of a gene caused by a mutation located in the same place on a chromosome.
"Although we've successfully genotyped a substantial number of TRs, that is still just a fraction of the total number in the human genome," said Wei Li, co-corresponding author. "Our next steps will be to prioritize the integration of a greater number of high-quality TR and include more underrepresented ancestries, such as Australian, Pacific Islander and Mongolian, as we move closer to realizing personalized precision medicine.