A method for positive forensic identification of samples from extremely low-coverage sequence data

Abstract

BackgroundDetermining whether two DNA samples originate from the same individual is difficult when the amount of retrievable DNA is limited. This is often the case for ancient, historic, and forensic samples. The most widely used approaches rely on amplification of a defined panel of multi-allelic markers and comparison to similar data from other samples. When the amount retrievable DNA is low these approaches fail.ResultsWe describe a new method for assessing whether shotgun DNA sequence data from two samples are consistent with originating from the same or different individuals. Our approach makes use of the large catalogs of single nucleotide polymorphism (SNP) markers to maximize the chances of observing potentially discriminating alleles. We further reduce the amount of data required by taking advantage of patterns of linkage disequilibrium modeled by a reference panel of haplotypes to indirectly compare observations at pairs of linked SNPs. Using both coalescent simulations and real sequencing data from modern and ancient sources, we show that this approach is robust with respect to the reference panel and has power to detect positive identity from DNA libraries with less than 1 % random and non-overlapping genome coverage in each sample.ConclusionWe present a powerful new approach that can determine whether DNA from two samples originated from the same individual even when only minute quantities of DNA are recoverable from each.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2241-6) contains supplementary material, which is available to authorized users.

Linkage disequilibrium matches forensic genetic records to disjoint genomic marker sets

“…Vohr et al (30) used SNPs to calculate likelihood ratiobased match scores, relying on a phased reference panel to assist in assigning low-coverage sequence reads to the same individual. Conceptually similar methods have also been used to identify mismatches between genotypes and expression data (31,32).…”

Linkage disequilibrium connects genetic records of relatives typed with disjoint genomic marker sets

“…This study contributes to a growing body of work on inference of genetic relationships in scenarios more challenging than when relatives are typed for the same markers [22][23][24][25][26]. In the setting of ancient DNA, Vohr et al [22] focused on the scenario in which DNA sequence is generated for different DNA samples possibly representing the same or related individuals-from a burial site, for example-but sequence is sufficiently sparse that reads do not necessarily overlap between samples.…”

“…This study contributes to a growing body of work on inference of genetic relationships in scenarios more challenging than when relatives are typed for the same markers [22][23][24][25][26]. In the setting of ancient DNA, Vohr et al [22] focused on the scenario in which DNA sequence is generated for different DNA samples possibly representing the same or related individuals-from a burial site, for example-but sequence is sufficiently sparse that reads do not necessarily overlap between samples. In a computation focused on detecting samples representing the same individual, Vohr et al [22] could distinguish simulated parent-offspring pairs and sib pairs from unrelated pairs; this computation amounts to demonstrating that under a same-individual hypothesis for ∆ test , pairs with a parent-offspring or sib relationship for ∆ true were uncovered.…”

“…In the setting of ancient DNA, Vohr et al [22] focused on the scenario in which DNA sequence is generated for different DNA samples possibly representing the same or related individuals-from a burial site, for example-but sequence is sufficiently sparse that reads do not necessarily overlap between samples. In a computation focused on detecting samples representing the same individual, Vohr et al [22] could distinguish simulated parent-offspring pairs and sib pairs from unrelated pairs; this computation amounts to demonstrating that under a same-individual hypothesis for ∆ test , pairs with a parent-offspring or sib relationship for ∆ true were uncovered. A second study formally estimating relatedness from sparse sequence data while making use of LD between sites with data available in different sampled individuals was able to identify second-and third-degree relative pairs [24].…”

Estimating Genetic Kin Relationships in Prehistoric Populations

“…Such approaches are promising for well-preserved 219 samples but these coverages might not be within reach for most aDNA studies. Other 220 methods specifically designed for ancient DNA data either require larger population 221 sample sizes than READ [50], large reference data sets [41,51] or are not directly 222 designed to identify relatives and estimate their degrees [52].…”