An object that is inequivalent to its own mirror image is said to be chiral. Famously embodied in the human hand, this property also applies to nucleic acids. A DNA molecule of any length is inequivalent to a reverse-orientation copy of itself yet, just like the right and left hands, the two are similar in every respect. We have developed synthetic DNA standards (‘sequins’) that are simply reverse-orientation copies of natural DNA sequences. Thanks to their common properties, sequins behave similarly to the original sequences on which they were based, but can be easily and unambiguously distinguished from human DNA by alignment to a reverse-orientation reference. In this way, sequins can be used as internal controls during DNA sequencing, or other genetic assays, to provide qualitative and quantitative measures of analytic performance. This design principle can be used to synthetically represent virtually any feature of the genome, including natural instances of genetic variation, disease causing mutations or analytically challenging features, such as microsatellites or mobile elements. We have created a suite of >500 sequin standards, 1-10kb in length, that have been validated for use in whole genome and targeted next-generation sequencing, third-generation nanopore sequencing, and other assays. Sequins fulfill the unmet need for reference standards suitable for clinical genomics, an important step toward the realization of personalized medicine.