How the ICMP is Using the Latest DNA Technology to Identify Missing Persons
Every year, millions of people around the world go missing as a result of conflict, human rights abuses, disasters, organized crime, irregular migration, and other causes. As the only international organization that is exclusively tasked to address this issue, the International Commission for Missing Persons (ICMP) is actively engaged in developing institutions and civil society capacity, promoting legislation, fostering social and political advocacy, and developing and providing technical expertise to locate and identify the missing.
In this interview, we speak with Michelle Peck, Research and Validation Manager at the ICMP Laboratory. She explains the challenges that come from identifying missing persons, such as working with limited degraded samples and locating close relatives for reference samples.
One way to increase the likelihood of making an identification is to use massively parallel sequencing (MPS) technology. Currently, ICMP is working on developing a MPS SNP panel containing over 1,400 SNPs that is specifically designed to meet these challenges. SNPs were selected, because they’re the smallest possible target, which makes them ideal for degraded DNA. The panel itself was designed to select tri-allelyic SNPs to maximize heterozygosity to use distant relatives.
As of September 2020, when this video was recorded, 17 individuals from the former Yugoslavia, who were previously unable to be identified have been matched using this new panel.
Laura: Hello and thank you for joining us for our annual video series from the International Symposium on Human Identification. Today, we’re speaking with Michelle Peck. Hi Michelle!
Michelle: Hi Laura, how are you?
Laura: I’m doing good. Thank you so much for joining us. Maybe you can tell our viewers a little bit about yourself.
Michelle: I’m Michelle Peck, and I work at the International Commission for Missing Persons, and I’m the Research and Validation Manager at the Laboratory.
Laura: Can you tell us a little bit more about ICMP?
Michelle: Yes, of course. The ICMP is an international organization, and we assist governments in identifying missing persons that may go missing due to conflicts, natural disasters, human rights abuses, and for various reasons. Some current contexts that were working in on would include the former Yugoslavia, and we have projects in Mexico, Brazil, and Iraq, to name a few. But our support is cross-cutting. We have legal assistance. We work with civil society organizations, and then of course, we give technical support for data systems to anthropology, and then of course, DNA testing.
Laura: Well, speaking on DNA testing, ISHI focuses on DNA, so maybe you can talk a little bit about the DNA lab at ICMP.
Michelle: Of course! The DNA lab is an ISO 17025 accredited laboratory. So, we do DNA profile testing, human identification through database kinship matching, and our main source of samples is post-mortem samples that are most often from bones or teeth samples. Of course, they can be quite challenging, and then (critical to kinship matching) is having family reference samples, which are also a big part of our testing. So, we profile those samples, which are most often blood samples or maybe buccal. Then we put those into our databases.
Laura: Wonderful. You know, I always like to get a little bit of backstory. How did you come to work at ICMP?
Michelle: Yeah, so I started at ICMP three years ago. This corresponded with a move for the whole organization, and actually the laboratory from Bosnia, which is actually where the organization was started. From the context of the war in the former Yugoslavia, that’s how the ICMP and the laboratory was created, or for what reason they were created. So, three years ago, the headquarters and the lab moved to the Netherlands, and were located in the Hague. So, my move to the ICMP corresponded with that, and there was also an emphasis on new technologies, particularly MPS (massively parallel sequencing). Formerly, I was at the Armed Forces DNA Identification Laboratory where I gained experience implementing MPS, so the timing worked well with the move of the lab and myself.
Laura: Wow, missing persons cases can be very complex. What are some of the challenges that you face?
Michelle: Yeah, so there are many challenges with missing persons cases. Of course, one of the biggest challenges is the type of samples that we’re dealing with. So, the post-mortem bone samples, as I mentioned. Those bone samples are often of low quantity, often can be of low quality (they may be degraded), and they may contain inhibitors – environmental conditions and the age of the samples can contribute to that. And while our methods are quite robust and effective, we still have situations where we are only getting partial STR profiles or failed profiles, so that is the biggest challenge.
One of the other challenges is with reference samples. As I mentioned for the kinship matching, one of the key components is to have the family references, because we’re not doing direct matching. There are two challenges with reference samples. One is actually finding the family members who have loved ones missing. So, that’s the reason that our organization works with governments and civil society organizations; to work with those families. But, as it relates to our testing, the other component or difficult part with reference samples is having close relatives. So, the kinship matching process is complex, but it works the best with close relatives. But when you have more distance relatives, such as a niece, nephew, or cousin, really with STRs, the kinship matching is impossible. Then, when you have both of those situations, with distant relatives and a difficult sample, that just makes the challenge even greater.
Laura: I can only imagine. Maybe we can talk a little bit about why DNA is the most useful for some of the work you’re doing and how some of the new technologies have impacted that.
Michelle: Right, so DNA is the most unique identifier of an individual, an often in cases (with the remains that we get) it may be the only option, because there isn’t other information. And with DNA, of course, we know genetic inheritance patterns. We have population statistics. And then also, with all that information, we can make identification with statistic basis, which is the most reliable to make an identification. So, DNA is the most reliable identifier, so that’s why we focus on that, and the success of the organization had in the former Yugoslavia was in using a DNA-led approach. As I mentioned, there are still very challenging missing persons cases for which STR testing is insufficient, and of course, those are the situations where we have challenging bone samples and distant relatives. So, for those samples, we’re working on developing a massively parallel sequencing SNP panel that contains over 1,400 SNPs so this panel was specifically designed to meet these challenges.
We selected SNPs, because they’re the smallest possible target, which is great for degraded DNA, and then the design of the panel selected SNPs that are tri-allelyic to maximize heterozygosity to use distant relatives. Then, the assay that we’re using for this is QIAGEN’s QIASEQ chemistry, and it incorporates a powerful feature called a unique molecular index or a UMI, and this is particularly useful for low quality samples, because what the UMI does is allow you to trace back from your sequencing data to the unique, original starting molecule. That’s critical for all samples, but particularly for difficult samples. As I said, it was designed to meet those challenges, so some of the evaluations we’ve done of the kit or the panel is to see how it works with distant relatives. So, when we look at matching simulations, for example, for a cousin, we’re able to get likelihood ratios sufficient for matching with this SNP panel, which wouldn’t be possible for STRs.
Laura: The technology is amazing! We’ve come such a long way in such a short time it feels like. How are you applying this MPS panel in particular?
Michelle: So our first application with the panel is with presumptive cases, so we’re using STR matching to identify potential matches where the statistics aren’t high enough to issue a match report with STRs, but it allows us to identify potential matches. So, we’re testing the relevant bone samples and the family reference samples with the MPS panel to work to get a match with that. But that is low throughput, so we’d really like to get it into more database kinship testing, where we have the bone samples with the SNPs in the database, and we have the family reference samples in the database to allow for the matching that occurs and the searching for matches with the SNP panel.
Laura: Ok, are there future applications that you see with this?
Michelle: Yeah, so if we can move to what I was just describing and we’re able to have these databases and be able to do a higher throughput method, both with the matching, but also thinking of the laboratory process, which is a long one, but if we can roboticize that and increase the throughput, we’re really going to be opening the door to be able to use this method on a high scale approach. Some contexts that we see it being particularly useful for: one is the missing migrants crisis, where access to close relatives is often a major limitation and another potential application is assistance to Vietnam, where there’s hundreds of thousands of missing and there’s a huge emphasis on working to identify those who perished in the war. And, in that context, there’s the lack of close relatives, and those samples are extremely challenging due to the environment there. And, again, the design of the MPS panel was designed to address these two issues, so being able to scale it up would really allow us to apply it to the context that it’s designed for.
Laura: Fantastic! Are there any stories that you’re able to share with us about MPS panel that you’re working with?
Michelle: Yeah, so I’m very excited to share some initial success that we’ve had with the panel. We’ve issued 17 match reports in relation to the continued efforts to identify the missing from the former Yugoslavia, and those are individuals that were not able to be identified with STRs, and one of our first cases is one of our most interesting (so far) and it involved three missing siblings, for which there were only two first cousins as family references for those missing persons. The matching expert in the lab actually did a lot of background research and investigation into the missing persons event that these bones were found at and looking at the family pedigrees of those that were missing from that event. So, there was strong evidence pointing that they were the three individuals that we suspected, but only when were able to do the MPS testing were we able to issue match reports for these three individuals, so that was really an exciting initial success and we’re excited to see how we can apply it to these other cases.
Laura: That’s wonderful! This work is so important. Is there any way that the public can work to support your work?
Michelle: Yes, of course. The best way is on social media, and we have Twitter, LinkedIn, and Facebook accounts. So, our handle for that is @TheICMP, so hopefully everyone can follow us and see the work that we’re doing and we’d love for people to reach out through those accounts.
Laura: Well, thank you so much for joining us. We really appreciate you taking the time to share more about your work.
Michelle: Yes, thank you Laura. It was a pleasure!
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