Impact of SNP microarray analysis of compromised DNA on kinship classification success in the context of investigative genetic genealogy

Jard H De Vries,Daniel Kling,Athina Vidaki,Pascal Arp,Vivian Kalamara,Michael M.P.J Verbiest,Danuta Piniewska-Róg,Thomas J Parsons,André G Uitterlinden,Manfred Kayser

doi:10.1016/j.fsigen.2021.102625

Abstract

Single nucleotide polymorphism (SNP) data generated with microarray technologies have been used to solve murder cases via investigative leads obtained from identifying relatives of the unknown perpetrator included in accessible genomic databases, an approach referred to as investigative genetic genealogy (IGG). However, SNP microarrays were developed for relatively high input DNA quantity and quality, while DNA typically obtainable from crime scene stains is of low DNA quantity and quality, and SNP microarray data obtained from compromised DNA are largely missing. By applying the Illumina Global Screening Array (GSA) to 264 DNA samples with systematically altered quantity and quality, we empirically tested the impact of SNP microarray analysis of compromised DNA on kinship classification success, as relevant in IGG. Reference data from manufacturer-recommended input DNA quality and quantity were used to estimate genotype accuracy in the compromised DNA samples and for simulating data of different degree relatives. Although stepwise decrease of input DNA amount from 200 ng to 6.25 pg led to decreased SNP call rates and increased genotyping errors, kinship classification success did not decrease down to 250 pg for siblings and 1st cousins, 1 ng for 2nd cousins, while at 25 pg and below kinship classification success was zero. Stepwise decrease of input DNA quality via increased DNA fragmentation resulted in the decrease of genotyping accuracy as well as kinship classification success, which went down to zero at the average DNA fragment size of 150 base pairs. Combining decreased DNA quantity and quality in mock casework and skeletal samples further highlighted possibilities and limitations. Overall, GSA analysis achieved maximal kinship classification success from 800 to 200 times lower input DNA quantities than manufacturer-recommended, although DNA quality plays a key role too, while compromised DNA produced false negative kinship classifications rather than false positive ones.

Highlights

For almost three decades, forensic DNA profiling with standard sets of polymorphic short tandem repeat (STR) markers has successfully been used to identify perpetrators of crime, thereby contributing to wards solving numerous criminal cases worldwide [1,2]
Aiming to evaluate Single nucleotide polymorphism (SNP) microarray technology for quantity and/or quality compromised input DNA and to test the consequence of resulting genotyping errors for kinship classification in the context of investigative genetic genealogy (IGG), we performed a series of SNP microarray experiments by applying the widely used Illumina Global Screening Array (GSA)
Our study provides the first systematically obtained empirical evi dence how SNP microarray analysis of quantity- and qualitycompromised DNA impacts on kinship classification success, which is highly relevant in the context of IGG

Summary

Introduction

Forensic DNA profiling with standard sets of polymorphic short tandem repeat (STR) markers has successfully been used to identify perpetrators of crime, thereby contributing to wards solving numerous criminal cases worldwide [1,2]. In principle, forensic STR profiling is unsuitable for identifying unknown perpetrators, whose STR profiles are not yet included in national forensic DNA databases or are unknown to the investigative authorities otherwise This leads to cold cases with STR profiles of crime scene stains being available but not matching any known suspect, including all criminal offenders stored in the national forensic DNA database. Several DNA-based approaches for tracing un known perpetrators have emerged One such way is to use the STRprofile of the unknown to search for family members of the unknown in the national forensic DNA database (i.e., familial search) [3]. Investigative genetic genealogy (IGG) has started to emerge as new approach to trace unknown perpetrators with the help of DNA [4,10]

Methods

Results

Discussion

Conclusion