Tandem Repeat Detection Using Next-Generation Mapping and Its Application in Detecting rDNA Copy Number Variation in Plant and Human Genomes

Eukaryotic genomes harbor large tandem repeats, such as rDNA repeats. Copy number variation of rDNA has been shown to correlate with global changes in gene expression. These repeat elements, as special genetic markers, are essential for genomic functions, disease diagnosis, and mapping studies. However, rDNA regions normally span several megabase, which is far beyond the accessibility of current NGS technologies.

The BioNano Genomics Irys® System images fluorescently labeled long DNA molecules of 150 kb to 1 Mb. The exceptional integrity of DNA provides us a method to accurately determine repeat copy numbers and identify boundaries for alignment to physical maps.

We present a robust tool (in development) for the detection of both simple and compound tandem repeats in complex genomes. We detected a 45S rDNA unit as a 5-label compound repeat and estimated their copy numbers in 36 human samples. In Arabidopsis and maize, 43S rDNA unit was detected as a 9-10 kb simple repeat, while in tomato genome, rDNA unit was detected as a two-label compound repeat. We further discovered rDNA copy number and unit size variances between wild and cultivated tomato samples. Molecules containing these repeats play vital roles in precisely locating the rDNA regions on the physical map.

Based on the genome annotations, we validated 83% and 68% of the compound repeats detected in Arabidopsis and maize at sequence level, respectively. We concluded that the tool was fast (8 gigabases per minute), accurate, and robust using the default parameters, single threaded.