Forensic investigative genetic genealogy using genotypes generated or imputed from transcriptomes

Daniel Kling; Alberte Honoré Jepsen; Marie-Louise Kampmann; Stine Bøttcher Jacobsen; Andreas Tillmar; Claus Børsting; Jeppe Dyrberg Andersen

doi:10.1016/j.fsigen.2025.103277

Forensic investigative genetic genealogy using genotypes generated or imputed from transcriptomes

Forensic Sci Int Genet. 2025 Mar 21:78:103277. doi: 10.1016/j.fsigen.2025.103277. Online ahead of print.

Authors

Daniel Kling¹, Alberte Honoré Jepsen², Marie-Louise Kampmann³, Stine Bøttcher Jacobsen³, Andreas Tillmar⁴, Claus Børsting³, Jeppe Dyrberg Andersen³

Affiliations

¹ Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway; Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden; Biostatistics (BIAS), Norwegian University of Life Sciences, Ås, Norway.
² Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: forensic.genetics@sund.ku.dk.
³ Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

PMID: 40121765
DOI: 10.1016/j.fsigen.2025.103277

Abstract

The utility of transcriptome analysis in forensic genetics is steadily increasing. The transcriptome, with its ability to reflect both transcript levels and their nucleotide sequences, is proving to be useful for a variety of different applications, including body fluid identification and donor assignment, thereby providing both genetic and contextual information. Furthermore, the substantial single nucleotide polymorphism (SNP) coverage obtainable with whole transcriptome sequencing may prove useful for additional applications. In this study, we expand the current knowledge of transcriptomics in forensic genetics by showing how RNA can be used for forensic investigative genetic genealogy (FIGG) purposes and inference of distant relationships. Genetic data was simulated for relationships ranging from full siblings (first-degree relatives) to third cousins (seventh-degree relatives). The sets of SNP genotypes were subsequently reduced to only include observed and imputed SNP genotypes at loci covered by transcriptome sequencing of whole blood. The relationships of relatives as distant as second cousins could be reliably classified based on an average of 99,548 SNPs. Appropriate thresholds for sequence quality parameters limited the rate of erroneous genotype calls, with the remaining errors proving to have little to no effect on relationship inference. In conclusion, we present a proof-of-concept study on how transcriptome-based genotypes, in combination with imputed genotypes, may be used for reliable relationship inference for FIGG purposes.

Keywords: Forensic investigative genetic genealogy; SNPs; Shotgun RNA sequencing; Whole transcriptome sequencing.