DNA identification by pedigree likelihood ratio accommodating population substructure and mutations

Abstract

DNA typing is an important tool in missing-person identification, especially in mass-fatality disasters. Identification methods comparing a DNA profile from unidentified human remains with that of a direct (from the person) or indirect (for example, from a biological relative) reference sample and ranking the pairwise likelihood ratios (LR) is straightforward and well defined. However, for indirect comparison cases in which several members from a family can serve as reference samples, the full power of kinship analysis is not entirely exploited. Because biologically related family members are not genetically independent, more information and thus greater power can be attained by simultaneous use of all pedigree members in most cases, although distant relationships may reduce the power. In this study, an improvement was made on the method for missing-person identification for autosomal and lineage-based markers, by considering jointly the DNA profile data of all available family reference samples. The missing person is evaluated by a pedigree LR of the probability of DNA evidence under alternative hypotheses (for example, the missing person is unrelated or if they belong to this pedigree with a specified biological relationship) and can be ranked for all pedigrees within a database. Pedigree LRs are adjusted for population substructure according to the recommendations of the second National Research Council (NRCII) Report. A realistic mutation model was also incorporated to accommodate the possibility of false exclusion. The results show that the effect of mutation on the pedigree LR is moderate, but LRs can be significantly decreased by the effect of population substructure. Finally, Y chromosome and mitochondrial DNA were integrated into the analysis to increase the power of identification. A program titled MPKin was developed, combining the aforementioned features to facilitate genetic analysis for identifying missing persons. The computational complexity of the algorithms is explained, and several ways to reduce the complexity are introduced.

Figure 1

Family pedigree. A, B, C, E and F are untyped family members; D, G, H and I are typed members. Untyped Connectors (UC) include A, B, E and F. G is an Offspring with Single Typed Parent (OSTP).

Figure 2

Pedigree to identify the missing person U. In this, C1 and C2 are the alleged children of U, F is alleged father, M is the alleged mother and S is the alleged spouse. M and S are not typed. S is an UC, whose genotype has to be inferred.

Figure 3

Family pedigrees with mutations. Comparison of log of pedigree (p) likelihood ratios for cases with and without mutation (m) and with and without population substructure (θ) given true identity (20,000 simulations). Mutation rate data are from the AABB [29].