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

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. In this report we describe a framework for accurately and robustly resolving whether individuals are in a complex genomic DNA mixture using high-density single nucleotide polymorphism (SNP) genotyping microarrays. We develop a theoretical framework for detecting an individual's presence within a mixture, show its limits through simulation, and finally demonstrate experimentally the identification of the presence of genomic DNA of individuals within a series of highly complex genomic mixtures. Our approaches demonstrate straightforward identification of trace amounts (<1%) of DNA from an individual contributor within a complex mixture. We show how probe-intensity analysis of high-density SNP data can be used, even given the experimental noise of a microarray. We discuss the implications of these findings in two fields: forensics and genome-wide association (GWA) genetic studies. Within forensics, resolving whether an individual is contributing trace amounts of genomic DNA to a complex mixture is a tremendous challenge. Within GWA studies, there is a considerable push to make experimental data publicly available so that the data can be combined with other studies. Our findings show that such an approach does not completely conceal identity, since it is straightforward to assess the probability that a person or relative participated in a GWA study.