Are microhaplotypes derived from the 1000 Genomes Project reliable for forensic purposes?

Area of Science:

• Forensic genetics
• Population genetics
• Genomics

Background:

• Microhaplotypes (MHs) are crucial genetic markers in forensic science.
• Previous research has not fully addressed phasing errors in MHs derived from the 1000 Genomes Project (1kGP).
• These errors can negatively impact forensic parameter evaluations and lead to inaccurate conclusions.

Purpose of the Study:

• To construct a comprehensive set of microhaplotypes across the human genome using expanded 1000 Genomes Project data.
• To evaluate the reliability of these MHs by investigating phasing errors.
• To assess the impact of minor allele frequency (MAF) thresholds on marker reliability.

Main Methods:

• Generation of an extensive microhaplotype set from 1kGP data aligned to GRCh38.
• Application of three MAF thresholds (0, 0.01, 0.05) for marker evaluation.
• Analysis of pedigree data from 602 trios across 18 populations to identify phasing errors.
• Targeted enrichment and next-generation sequencing of 50 MHs for a Southern Han Chinese trio.

Main Results:

• Phasing errors were confirmed in 1kGP-derived MHs using next-generation sequencing.
• The probability of phasing errors positively correlated with marker effective number of alleles (Ae) and informativeness (In).
• Mismatch probabilities differed significantly across continental populations, and certain genomic regions (e.g., MHC) showed higher error rates.

Conclusions:

• Sole reliance on 1kGP sequencing data for forensic MH analysis may be unreliable due to phasing errors.
• Implementing MAF filtering and avoiding problematic genomic regions can mitigate error occurrence.
• Thorough validation of MH forensic parameters is essential for ensuring marker reliability in forensic applications.