Developing criteria and data to determine best options for expanding the core CODIS loci

Abstract

Background: Recently, the Combined DNA Index System (CODIS) Core Loci Working Group established by the US Federal Bureau of Investigation (FBI) reviewed and recommended changes to the CODIS core loci. The Working Group identified 20 short tandem repeat (STR) loci (composed of the original CODIS core set loci (minus TPOX), four European recommended loci, PentaE, and DYS391) plus the Amelogenin marker as the new core set. Before selecting and finalizing the core loci, some evaluations are needed to provide guidance for the best options of core selection.

Method: The performance of current and newly proposed CODIS core loci sets were evaluated with simplified analyses for adventitious hit rates in reasonably large datasets under single-source profile comparisons, mixture comparisons and kinship searches, and for international data sharing. Informativeness (for example, match probability, average kinship index (AKI)) and mutation rates of each locus were some of the criteria to consider for loci selection. However, the primary factor was performance with challenged forensic samples.

Results: The current battery of loci provided in already validated commercial kits meet the needs for single-source profile comparisons and international data sharing, even with relatively large databases. However, the 13 CODIS core loci are not sufficiently powerful for kinship analyses and searching potential contributors of mixtures in larger databases; 19 or more autosomal STR loci perform better. Y-chromosome STR (Y-STR) loci are very useful to trace paternal lineage, deconvolve female and male mixtures, and resolve inconsistencies with Amelogenin typing. The DYS391 locus is of little theoretical or practical use. Combining five or six Y-chromosome STR loci with existing autosomal STR loci can produce better performance than the same number of autosomal loci for kinship analysis and still yield a sufficiently low match probability for single-source profile comparisons.

Conclusion: A more comprehensive study should be performed to provide the necessary information to decision makers and stakeholders about the construction of a new set of core loci for CODIS. Finally, selection of loci should be driven by the concept that the needs of casework should be supported by the processes of CODIS (or for that matter any forensic DNA database).

Figure 1

The log₁₀ of the kinship index (KI) distributions for parent/child (PC) or full-sibling (FS). Log₁₀(KI) distributions for parent/child (PC) or full-sibling (FS) identified as unrelated profiles and unrelated identified as potential related profiles. (A) The new FBI core loci in section A (20 STR loci); (B) the 13 current CODIS core loci. In total, 1 million simulations were performed for each distribution. The KI of the DYS391 locus for true relatives is 2.2. The distributions of true parent/child distributions with or without the DYS391 locus are close, as were the true full-sibling distributions.

Figure 2

The distributions of the number of included profiles in a two-person mixture based on autosomal STRs for four panels. The four panels were the 13 CODIS core loci, the 19 autosomal loci in section A, the 10 most informative of the 13 CODIS core loci (D18S51, FGA, D21S11, D8S1179, VWA, D7S820, D3S1358, TH01, D13S317, and D16S539), and the 10 least informative of the 13 CODIS core loci (D8S1179, VWA, D7S820, D3S1358, TH01, D13S317, D16S539, CSF1PO, D5S818, and TPOX). The distributions were obtained by simulation, in which 1 million profiles were first generated as a database, and then 1 million two-person mixtures were randomly generated without replacement. Each mixture was searched against the database to determine the number of candidate part-contributors beyond those that comprised the mixture. The Y-axis represents the proportion of mixtures with specific number of candidate contributors in a database search. For example, with 13 CODIS loci, no candidate contributors were identified for 67.7% of mixtures. Only 1.3% or 0.4% of two-person mixtures generated more than 10 or 20 candidate contributors, respectively. With the 19 loci in section A, almost 100% of two-person mixtures had no candidate contributors in a database of 1 million profiles.

Figure 3

The log₁₀ of the average kinship index (AKI) distributions of full-sibling and parent/child relationships. Log₁₀(AKI) distributions of full-sibling and parent/child relationships with the most informative autosomal and Y-chromosome STRs (Y-STRs) in Tables 1 and 4. The horizontal axis labels are '14 auto- + 6 Y-STRs' to '18 auto- + 2 Y-STRs' which are the combinations of a specified number of the most informative autosomal STRs in section A (except for the D12S391 locus, because this locus is linked with the VWA locus) and a specified number of the most informative Y-STRs. The term '19 auto- + 1 Y-STRs' refers to all 19 autosomal STR loci in section A and the most informative Y-STR (DYS385). Independence between D12S391 and VWA was assumed in calculation of AKI values of '19 auto- + 1 Y-STRs'. In all calculations, the D5S818 and CSF1PO loci were assumed to be independent (although current data do not support the assumption). The true AKI of '19 auto- + 1 Y-STRs' should be slightly lower.