Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays

TLDR

The study discusses the implications of its findings. The study aims to use high‑density SNP microarrays to develop a theoretical framework, simulate limits, and experimentally demonstrate detection of individuals contributing as little as 0.1% of DNA in complex mixtures. The authors develop a theoretical framework, perform simulations to assess limits, and experimentally test detection of individuals in highly complex mixtures using high‑density SNP microarrays. The method enables accurate identification of trace contributors in forensic mixtures, revealing that SNPs can detect individuals contributing less than 0.1% of DNA and that composite statistics do not mask identity in genome‑wide association studies.

Abstract

We use high-density single nucleotide polymorphism (SNP) genotyping microarrays to demonstrate the ability to accurately and robustly determine whether individuals are in a complex genomic DNA mixture. We first develop a theoretical framework for detecting an individual's presence within a mixture, then show, through simulations, the limits associated with our method, and finally demonstrate experimentally the identification of the presence of genomic DNA of specific individuals within a series of highly complex genomic mixtures, including mixtures where an individual contributes less than 0.1% of the total genomic DNA. These findings shift the perceived utility of SNPs for identifying individual trace contributors within a forensics mixture, and suggest future research efforts into assessing the viability of previously sub-optimal DNA sources due to sample contamination. These findings also suggest that composite statistics across cohorts, such as allele frequency or genotype counts, do not mask identity within genome-wide association studies. The implications of these findings are discussed.