Our study of microhaps grew out of our earlier demonstration of mini-haplotypes of up to 10 kb in extent [17], linguistically paralleling the early transition in forensics from minisatellites to microsatellite loci. These loci were chosen to be comprised of multiple SNPs within small enough segments of DNA that they could be phased by single sequencing reads. By limiting size to the length of NGS reads, we have identified phased loci that maximize information content in the smallest length of DNA, highly

suitable for forensic applications where DNA is degraded. By using SNPs instead of STRPs, we have greatly reduced the potential for analysis error which accompanies STRP typing of degraded DNA (allele dropout, stutter peaks, identification of MEK inhibitor a mixture). While we are not proposing this initial panel of 31 unlinked microhaps as a final panel for forensic implementation, it might find some immediate Selleckchem MK-2206 limited applications in actual forensic work when degradation of biological samples or other conditions do not allow the use of standard STRPs. Another value of sequencing is that rare variants will be seen when one occurs within a microhap. As the 1000 Genomes project has shown, there are many rare variants seen once

or only a few times. Such a rare variant will define an essentially unique allele that will make inference of biological relationship virtually certain, at least based on that locus, but will not necessarily define the nature of the relationship. enough Although such rare variants will be missed when the SNPs are typed individually and phased statistically, the low mutation rates for SNPs and nearly zero recombination rates across these small DNA segments allow high levels of resolvability of the microhap genotypes. At this

stage of development it is not possible to compare this panel to the CODIS markers for the ability to infer a biological relationship because our populations have not been typed for both sets of markers. While these microhaps are individually less good (fewer alleles, lower heterozygosity) than the majority of the CODIS markers, we have already identified and characterized more loci than are included in the expanded CODIS panel. Each multiallelic microhap is clearly more informative on relationships than an individual di-allelic SNP [34]. The nature of kinship statistics makes it clear that loci such as these microhaps have relevant information [26]. When more such loci are documented, it will be important to determine which individual loci and which combinations of loci are better at familial identification. In the meantime, our analyses demonstrate the utility of the 31 unlinked microhaps for diverse studies, both forensic and anthropological, beyond familial inference. The PCA, tree, and STRUCTURE analyses (Fig. 3 and Supplemental Figs.