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Improving human forensics through advances in genetics, genomics and molecular biology

A Corrigendum to this article was published on 29 August 2012

This article has been updated

Key Points

  • Forensic DNA profiling based on short tandem repeat (STR) markers currently allows the identification of persons already known to the investigating authorities. This technology has recently been improved in terms of the ability to analyse degraded DNA and low amounts of DNA, and has increased discrimination power.

  • There are still some technical limitations to STR profiling, some of which can be overcome by using SNPs, which are more suitable for dealing with highly degraded DNA. Although the existing STR-based forensic DNA databases make it unlikely that SNPs will replace STRs for universal identification, SNPs are likely to improve human identification in disaster victim identification and in kinship analysis.

  • The limitation of currently used Y-chromosomal STRs (Y-STRs) for male identification from male/female mixed samples is that it only allows the identification of groups of paternally related males. This can be overcome by applying rapidly mutating Y-STRs that provide male relative differentiation in many cases, allowing individual male identification via Y chromosome analysis.

  • STR or SNP profiling can only identify persons previously known to the investigating authorities, a limitation that could be solved by forensic DNA phenotyping; that is, the inference of externally visible traits and biogeographic ancestry from crime scene DNA to provide intelligence leads for a police investigation that is searching for unknown persons.

  • DNA-based biogeographic ancestry inferences are already possible on the level of at least larger geographic regions such as continents, and partly on subregional levels, using suitable SNPs that also allow the reconstruction of mixed ancestry. DNA-based inferences with a resolution of single countries are unlikely to ever become available.

  • Current DNA-based appearance prediction includes group-specific traits such as eye colour, hair colour and age with categorical prediction accuracies suitable for practical applications, and additional group-specific traits such as skin colour, hair morphology or baldness may follow. Individual-specific DNA-based facial morphology prediction would be most appreciated for finding unknown persons, but is currently beyond our level of genetic knowledge.

  • mRNA-based determination of the cellular origin of a crime scene sample, as is now possible for most relevant tissues in forensic practice, including skin, provides more accuracy than previously used presumptive methods. The use of DNA methylation markers for this purpose appears promising.

  • Estimating the deposition time of a crime scene blood sample by using circadian biomarkers has become possible, although more markers are needed for detailed timing. Furthermore, estimating sample age based on differential RNA degradation appears promising.

  • Future prospects include using next-generation (PCR-free) sequencing technologies to improve human identification in heavily degraded and mixed samples, more detailed DNA reconstruction of human appearance to allow stringent concentration of police investigation in the search for unknown suspects, and more detailed molecular approaches for crime scene reconstruction, such as in sample deposition timing and perhaps in the reconstruction of the physiological conditions of victims and perpetrators during criminal acts.

Abstract

Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.

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Figure 1: Autosomal SNPs suitable for universal human identification.
Figure 2: Genetic substructure of human populations.
Figure 3: DNA-based prediction of human eye colour.
Figure 4: Differentiation of forensically relevant body fluids using genome-wide microRNA expression data.

Change history

  • 29 August 2012

    In Figure 3 of this article, the red box surrounding the second, third and fourth eyes in the third column was incorrectly positioned. The box should surround the third, fourth and fifth eyes in the third column. The authors and editors apologize for the error.

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Acknowledgements

We highly appreciate the contribution of P. Sankar and B.-J. Koops to box 2 on ethical aspects, and box 3 on legal implications of forensic DNA phenotyping, respectively. We are also very grateful to A. Pakstis and K. K. Kidd for providing data used in figure 1. We thank O. Lao, D. Zubakov, R. Koppenol and S. Walsh for preparing figures, as well as K. Ballantyne for help in literature survey. K. Ballantyne, P. Schneider and R. van Oorschot are gratefully acknowledged for valuable comments on an earlier version of the manuscript. We apologize to those colleagues whose work we were unable to cite owing to space restrictions. The work of the authors is supported by the Netherlands Forensic Institute, the Erasmus University Medical Center Rotterdam (M.K.), the Leiden University Medical Center (P.d.K.), and additionally by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) within the framework of the Forensic Genomics Consortium Netherlands (FGCN).

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FURTHER INFORMATION

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23andMe

Centre d'Etude du Polymorphisme Humain (CEPH) Database

deCODEme

Human Genome Diversity Project

Y Chromosome Haplotype Reference Database

Glossary

Short tandem repeat

A DNA sequence containing a variable number (typically ≤50) of tandemly repeated short (2–6 bp) sequence motifs, such as (GATA)n. Forensically used STRs are usually tetranucleotide repeats, which have few stutter artefacts (see below).

Forensic DNA databases

National databases held by the police or the justice system of defined short tandem repeat profiles, usually from persons convicted of a defined crime.

Single nucleotide polymorphisms

DNA sequence variation concerning a single site (base pair) in the genome. The polymorphism is usually a substitution, but can sometimes be a single base pair insertion or deletion.

Biogeographic ancestry

A concept of lineage that looks at kinship and descent based on biogeography, a combination of biology and geography.

Low template DNA

The availability of just a few DNA molecules for DNA profiling.

Allele drop-in

Addition of (typically) one or two alleles to a DNA profile, owing to contamination.

Allele drop-out

Loss of one or both alleles in a DNA profile, owing to stochastic failure of PCR amplification, usually when the number of template molecules is small.

Heterozygote peak imbalance

The proportion of the two alleles of a heterozygote genotype, expressed as the area of the smaller peak divided by the area of the larger peak in an electropherogram.

PCR amplicon

DNA that is generated by PCR amplification.

Stutter artefacts

Artefacts that occur by DNA-replication slippage during the PCR amplification of STRs. Most stutter artefacts seen with fluorescence-based STR analysis are one repeat shorter than the true allele.

Multiplex genotyping

Simultaneous analysis of multiple genetic loci.

Match probability

The chance of two unrelated individuals sharing a DNA profile.

Population differentiation

Populations that differ to a certain extent in their genetic characteristics.

Haplotype

A specific Y chromosome or mitochondrial (mt) type defined by the combination of genotypes of more rapidly evolving markers, usually STRs on the Y chromosome for Y haplotypes, and the mtDNA sequences — including rapidly and slowly evolving sites — for mtDNA haplotypes.

Bottleneck event

A marked reduction in population size followed by the survival and expansion of a small, random sample of the original population. It often results in the loss of genetic variation and more frequent matings among closely related individuals.

Founder event

A situation in which a new population is founded by a small number of incoming individuals. Similar to a bottleneck, the founder effect severely reduces genetic diversity, increasing the effect of random drift.

Genetic clusters and clines

Populations in close geographic proximity that have similar genetic characteristics (clusters), or populations that show a genetic frequency gradient that correlates with the geographic distances separating them (clines).

Effective population size

The number of breeding individuals of an idealized population that has the same properties with respect to genetic drift as does the actual population in question.

Genetic drift

The stochastic fluctuation of allele frequencies in a population owing to chance variations in the contribution of each individual to the next generation.

Residence pattern

Referring to conventional rules or patterns of behaviour concerning the place a couple lives after marriage.

Haplogroup

A specific Y chromosome or mitochondrial type defined by the combination of genotypes of slowly evolving binary markers usually SNPs on the Y chromosome or mtDNA, respectively.

Hypervariable region

Part of mitochondrial DNA that is non-coding and therefore accumulates variation more than the coding parts.

Intelligence-led policing

A strategic, future-oriented and targeted approach to crime control, focusing upon the identification, analysis and 'management' of persisting and developing 'problems' or 'risks'.

Genetic admixture

The process of mixing of two or more groups whose ancestors had been separated (usually long before).

Genetic population substructure

The absence of random mating within a population, leading to allele frequency differences among subpopulations.

Ancestry-informative or ancestry-sensitive DNA markers

DNA markers that show marked allele frequency differences between populations from different geographic regions, and are therefore useful for determining the probable biogeographic ancestry of an individual.

Principle component analysis

A multivariate analysis that provides a new coordinate system, the axes of which (the principal components) successively account for the maximum amount of variance and are uncorrelated with each other.

Laplacian eigenvector

An analysis which — compared with, for example, principal component analysis (PCA) — is a statistical tool one can use to achieve dimension reduction of highly complex sets of (genetic) data. It has a major advantage over PCA in that it compares each individual only with its close neighbours, rather than with all other individuals (here, closeness refers to genetic relatedness, not geographic distance).

Multidimensional scaling analysis

A dimensionality reduction technique, similar to principal component analysis, in which points in a high-dimensional space are projected into a lower-dimensional space while approximately preserving the distance between points.

Genetic distance matrices

A matrix of values expressing the degree of genetic differentiation between two or more populations (or individuals).

Bayesian cluster algorithms

A probabilistic technique for evaluating the grouping of individuals or populations. Hypotheses are evaluated by their posterior probabilities.

Relative admixture proportions

The relative contribution of two or more parental populations to a hybrid population.

Genome-wide association studies

Analysis across the genome using association models to identify regions that contribute to genetic variation in a phenotype. These studies typically analyse data from high-density SNP arrays.

Skin reflectance

Measurable light reflectance of the skin, which depends (among other things) on skin pigmentation.

DNA methylation

A DNA modification in which a methyl group is added to cytosine. Methylation inhibits gene expression and is maintained through DNA replication and cell division.

TaqMan RT-PCR

A proprietary system (developed by Applied Biosystems) that allows the progression of a PCR reaction to be monitored in real time.

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Kayser, M., de Knijff, P. Improving human forensics through advances in genetics, genomics and molecular biology. Nat Rev Genet 12, 179–192 (2011). https://doi.org/10.1038/nrg2952

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