<p>DIP-STRs are genetic markers that combine low mutation deletion/insertion polymorphisms (DIP) with closely associated high mutation short tandem repeats (STRs). These were initially developed for targeting the minor donor in imbalanced two-person mixtures but have recently been explored as ancestry informative markers due to their combination of fast- and slow-evolving polymorphisms. This study aimed to evaluate for the first time the performance of a small set of 10 DIP-STR markers in predicting the ancestry of 100 individuals of self-reported African American, European American, East Asian American, and Southwest Hispanic origin. To characterize the genetic structure of the four populations of interest in STRUCTURE software, 557 previously genotyped HGDP-CEPH samples for the same 10 DIP-STR markers were used as major reference populations for the four major U.S. populations tested. Overall, haplotype diversity was observed among the four population groups for the 10 DIP-STR markers, reporting a total of 116 haplotypes, with 44.8% present across the groups. Common haplotypes were identified for each DIP-STR, as well as unique haplotypes observed only in specific population groups. The tested African American, European American, and East Asian American samples clustered into their respective African, European, and East Asian populations, albeit with some noise, while the Southwest Hispanic group exhibited admixture, as expected. These findings align with results from HGDP-CEPH reference samples, emphasizing that this small set of 10 informative DIP-STR markers can effectively distinguish the four U. S. population groups studied.</p>