Description of original award (Fiscal Year 2015, $585,415)
As submitted by the proposer:
Mixture evidence is increasing and far more complex cases are being encountered. Unfortunately, a portion of these complex mixtures are being deemed inconclusive or are being assessed with low statistical strength. Statistics packages have been developed and are being developed to address complex mixtures; but even these have limitations. As with any DNA typing system statistical methods cannot make a limited DNA profile better than it is. There is a need to develop analytical systems that make mixtures less complicated. Analytical and statistical approaches can work together to enhance mixture interpretation capabilities. Massively parallel sequencing (MPS) could facilitate mixture interpretation and simplify some complex mixtures. The value of MPS is its high throughput and the ability to provide sequence variation in addition to the nominal length of STR alleles, thereby, increasing the power of discrimination and potentially resolving contributors in mixtures that share alleles or share an allele and stutter product. We propose to identify additional sequence variation in STRs to facilitate mixture interpretation. The studies include describing allele sequence variation of those STRs of the CODIS core set and generally used Y STRs. The analyses include 1) identification and description of the type of variation(s) that exist at these STRs; 2) population studies to determine the frequency of the novel alleles; and 3) determination of the degree of retaining the variation observed in a true allele in its accompanying stutter product. Then, novel autosomal STRs and Y-STRs will be sought to expand markers that would better facilitate mixture interpretation. There is a wealth of STRs, available on the internet, yet to be screened for such variation. While identifying those markers with more alleles based on length only would seem sufficient, markers containing intra-allelic SNPs that display similar high heterozygosity are more desirable for forensic purposes. For the former, the greater number of alleles translates into potential heterozygotes where a large size difference of alleles of heterozygotes can result in substantial preferential amplification of the smaller sized allele. A similarly discriminating locus due to the presence of intra-allelic SNPs could have fewer large difference size heterozygote alleles and thus demonstrate less preferential amplification. Lastly, the software STRait Razor v 2.0 has been a tool that has facilitated worldwide STR typing from MPS data. STRait Razor v 3.0 will integrate flanking region SNP variation using associated variant-calling software, be validated, and made available freely.
This project contains a research and/or development component, as defined in applicable law.
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