High resolution of complex kinship cases using a dense SNP array

Forensic Investigative Genetic Genealogy (FIGG) has emerged as a powerful tool for solving cold cases through the analysis of dense SNP data. FIGG methodologies provide higher sensitivity by detecting a larger fraction of the genome that relatives share compared to standard analysis. This study evaluates the suitability of the Axiom™ Spain Biobank Array (Thermo Fisher Scientific, TFS), which consists of 756,834 SNPs, and it is typically used in biomedical research, for distant kinship inference and its performance in forensic samples. Therefore, considering the commonly encountered incomplete profiles and the high number of SNPs needed to solve distant kinship cases with FIGG approaches, we explored the performance of genotype imputation and refinement in low-quality samples and its impact on kinship analysis. Given the high SNP density of the Axiom array, we assessed whether it could also yield forensic leads regarding phenotype prediction, biogeographical ancestry, and mitochondrial and Y haplotypes. A total of 91 samples were analysed, including samples from i) individuals with known kinship relationships spanning from direct to 7^th degree; ii) individuals of diverse biogeographical ancestries and phenotypes; iii) bone samples of varying post-mortem intervals, and iv) two DNA controls. Kinship analysis was performed using the KING approach, segment analysis and likelihood analysis. While the KING approach failed to distinguish relationships beyond third degree, the combination of segment and likelihood analyses successfully resolved most of the distant kinship cases, from third to seventh degree (with the exception of 2 out of 29 cases). Imputation of simulated low-quality datasets resulted in a small error rate, with accuracy decreasing as SNP input declined. Imputation improved performance in segment-based analyses, which require high SNP density to detect shared genomic regions. Genotype refinement was performed in challenging forensic samples aiming to determine the reliability of the obtained genotypes. However, considering that degraded samples produced unreliable genotypes, and refinement did not significantly improve data quality, the array is not suitable for the analysis of skeletal remains and low-quality samples. The SNP array also enabled inference of biogeographical ancestry and mitochondrial and Y-chromosome haplotypes, whereas prediction of externally visible characteristics showed lower accuracy. These findings highlight both the potential and limitations of high-density SNP arrays for FIGG in forensic contexts, particularly when working with compromised DNA.