Implications of uniparental disomy in forensic kinship testing: A case study of paternal isodisomy on chromosome 3

Abstract

In typical inheritance, a child receives one chromosome of each pair from each parent. In rare cases, however, both chromosomes may be inherited from the same parent, a phenomenon known as uniparental disomy (UPD). In forensic kinship testing, UPD can lead to Mendelian inconsistencies between parent and child, increasing the risk of inconclusive or erroneous interpretations. In this case study, inconsistencies between the mother and child during paternity testing prompted further investigation. Parentage was confirmed (probability of maternity and paternity >99.99%), using autosomal short tandem repeat (STR) typing. Additional analyses were performed, including STR sequencing via next‐generation sequencing (NGS) and single nucleotide polymorphism (SNP) microarray testing across all trio samples. A total of 4 STRs and 273 SNPs on Chromosome 3 were examined, confirming complete paternal isodisomy in the child. Alternative kinship scenarios were then evaluated to assess the impact of UPD on relationship testing. While paternity results remained conclusive, maternal and secondary relationship analyses produced inconclusive and false outcomes, even when up to 42 STR loci were included. This study highlights the importance of recognizing UPD and its genotypic features in forensic casework. To mitigate the risk of misinterpretation, forensic scientists should remain vigilant for multiple inconsistencies restricted to a single chromosome, supported by the implementation of software alerts designed to flag such patterns.