Pairwise relatedness testing in the context of inbreeding: expectation and variance of the likelihood ratio

In this paper we investigate various effects of inbreeding on the likelihood ratio (LR) in forensic kinship testing. The basic setup of such testing involves formulating two competing hypotheses, in the form of pedigrees, describing the relationship between the individuals. The likelihood of each hypothesis is computed given the available genetic data, and a conclusion is reached if the ratio of these exceeds some pre-determined threshold. An important aspect of this approach is that the hypotheses are usually not exhaustive: The true relationship may differ from both of the stated pedigrees. It is well known that this may introduce bias in the test results. Previous work has established formulas for the expected value and variance of the LR, given the two competing hypotheses and the true relationship. However, the proposed method only handles cases without inbreeding. In this paper we extend these results to all possible pairwise relationships. The key ingredient is formulating the hypotheses in terms of Jacquard coefficients instead of the more restricted Cotterman coefficients. While the latter describe the relatedness between outbred individuals, the more general Jacquard coefficients allow any level of inbreeding. Our approach also enables scrutiny of another frequently overlooked source of LR bias, namely background inbreeding. This ubiquitous phenomenon is usually ignored in forensic kinship computations, due to lack of adequate methods and software. By leveraging recent work on pedigrees with inbred founders, we show how background inbreeding can be modeled as a continuous variable, providing easy-to-interpret results in specific cases. For example, we show that if true siblings are subjected to a test for parent-offspring, moderate levels of background inbreeding are expected to inflate the LR by more than 50%.

An evaluation of the SureID 23comp Human Identification Kit for kinship testing

Short tandem repeat (STR) profiling has been routinely used in kinship testing since the introduction of commercial kits in the mid-1990s. While 15 to 23 STR loci normally give definitive results in simple kinship testing, additional loci are sometimes required to resolve complex cases. The SureID 23comp Human Identification Kit, recently released by Health Gene Technologies (China), multiplexes amelogenin and 22 autosomal STRs, 17 of which are non-CODIS STRs. This enables the profiling of 38–40 loci when used in conjunction with widely used commercial kits. In this study, the kit was evaluated for kinship applications as a supplementary STR kit following the minimum criteria for validation recommended by the European Network of Forensic Science Institutes (ENFSI) and the Scientific Working Group on DNA Analysis Methods (SWGDAM) using 500 samples. Performance was comparable with other commercial kits demonstrating: repeatability and reproducibility; precision (maximum s.d. 0.1048 nt); accuracy, all alleles were within ±0.41 nt compared to the actual sizes; heterozygous peak balances at all loci >68%; stutter ratios ranged from 3.8% to 16.15%; full profiles were generated with 125 pg DNA (95.12% of alleles at 62 pg),; and we found 100% concordance over 5 common STRs with the GlobalFiler kit.