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Forensic DNA Phenotyping of Adult Body Height Current Scientific and Technical Knowledge and Recommendations for Future Research

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Forensic DNA Phenotyping of Adult Body Height Current Scientific and Technical Knowledge and Recommendations for Future Research Forensic DNA phenotyping of adult body height Current scientific and technical knowledge and recommendations for future research Melde Witmond (student ID 11285699) Literature thesis Master Forensic Science January 2018 Supervisor: Prof. dr. Ate Kloosterman Co-assessor: Dr. ir. Huub Hoefsloot Abstract Forensic DNA phenotyping (FDP) is the prediction of externally visible characteristics (EVCs), such as eye colour or height, from a DNA sample. FDP has the potential to provide a profile of the EVCs of an individual, which could produce new leads in a police investigation. Reliable prediction is already possible for some EVCs, namely eye and hair colour; expanding the EVCs that can be predicted would increase the value of FDP in an investigation. Body height prediction would provide particularly useful information, as it is easily observed by witnesses and difficult to manipulate. Therefore, this literature study aims to create an overview of the research into adult body height prediction and to provide recommendations on how to proceed towards implementation of height prediction into forensic practice. Genotype-phenotype relations are pivotal for accurate predictions from DNA. Deploying several approaches, almost 700 common and over 80 rare variants have been associated with height, which together explain approximately 27,4% of height heritability. Several studies have attempted to predict height using the variants known at that time, with promising results. However, a height prediction model has not yet been developed. There are FDP prediction models available for other EVCs, such as the HIrisPlex model and the Identitas v1 Forensic Chip. These models should serve as guides for the development of a prediction model for height. Thus, research into FDP of adult body height is still far from implementation into practice, but a promising start has been made, and much of the necessary knowledge for the development of a prediction model is available. Although research into the genotype-phenotype relations and prediction of height is important, future research should focus on the development of a reliable multi-trait prediction model that includes height, eye and hair colour, biogeographical ancestry and biological sex. Keywords: forensic intelligence, forensic DNA phenotyping, prediction, adult body height, externally visible characteristics, genotype-phenotype relations 1 Contents Abstract 1 Contents 2 1. Introduction 3 2. Research into forensic DNA phenotyping 4 2.1 Research methods for genotype-phenotype relations 4 2.2 Development and validation of a forensic prediction model 6 2.3 Legal and ethical considerations 8 3. Genotype-phenotype relations of adult body height 10 3.1 Common variants 10 3.2 Rare variants 11 3.3 Biological pathways and processes 12 4. Prediction of adult body height 14 4.1 Research done into height prediction 14 4.2 Other FDP models as examples 16 5. Conclusions and recommendations 19 5.1 Conclusions 19 5.2 Recommendations 19 References 22 Appendix: Search strategy 24 2 1. Introduction In forensic DNA phenotyping (FDP), certain traits of a donor are predicted from the DNA by genotyping loci that are linked to specific phenotypes1. DNA phenotyping can be used to predict many traits; in the biomedical field, it is usually applied to predict diseases2, while in the forensic field, it can be used to determine externally visible characteristics (EVCs) such as eye and hair colour1,3–5. Other EVCs that have a genetic factor, and thus can be predicted from DNA, are biological sex3, hair structure6, skin colour7,8, facial features9 (e.g. eye distance, chin shape), age10, and body height11,12. Some researchers include biogeographical ancestry as EVC, while others argue that you cannot observe someone’s genetic origin, and it is therefore not an EVC1. FDP can be used to compile a profile of the EVCs of the donor, which could be a great addition to the police investigation, especially when there is an unknown individual and when conventional DNA methods fail3. Currently, when crime scene material containing DNA is found, short tandem repeat (STR) analysis is performed to obtain a DNA profile that can be used for identification of the donor by comparison to reference profiles or a DNA database. However, if no DNA profile match is found, the police investigation might come to a standstill, especially when there is limited other evidence1,3,4. In these cases, FDP and the subsequent EVC profile could provide new insights and leads in the investigation, for example in narrowing down the list of possible individuals to only those matching the EVC profile. FDP could be particularly helpful in cases where skeletonised human remains are discovered or in cases where an unknown perpetrator left a DNA-containing trace. Thus, FDP might be the solution to furthering criminal investigations that have come to a standstill or reopening cold cases. Although, current knowledge on FDP can only reliably predict limited phenotypes of a few EVCs1, for example only blue and brown eye colour and only red, blond and brown hair colour. If a trace is small, which it often is in forensic cases, it is undesirable to waste sample material on a test that gives limited or no useful information. If more research is done into the genotype-phenotype relations of EVCs, more EVCs can be reliably predicted, and a more informative test can be developed. As many researchers are performing their own studies on trait prediction, both in the biomedical field and the forensic field, it is important to create an overview of research done so far. This will allow for better understanding of what is still to be researched before FDP can be applied in forensic practice. Such an overview should be created for each EVC, although this would be too much for one study. Thus, in this literature study, I will focus on one EVC, adult body height, for several reasons. First of all, biological sex, eye colour, hair colour and skin colour have been extensively researched, while the research into the genotype-phenotype relations of body height is upcoming. EVCs such as hair structure and facial features have not been studied as much, and thus, an overview is not yet needed. Secondly, although height is a more complex trait than eye and hair colour, it is less complex than facial features. This makes body height the logical next EVC to investigate thoroughly, after eye and hair colour. Thirdly, body height can give information that is very relevant to a police investigation, compared to other EVCs; height is more easily observable than eye colour, it is not as easy to change as hair colour, and it has less racial and ethical issues than skin colour. As it is my opinion that including adult body height in an FDP analysis would be of great value, this literature study will provide an overview of the research so far on body height and give recommendations on how to progress with the research and development of a prediction model. The research question of this study is, therefore: “How far from implementation into practice is the research into forensic DNA phenotyping of adult body height?”. To answer this research question, forensic DNA phenotyping in general will first be discussed in more depth. Then, the genotype- phenotype relations of body height will be described. This is followed by a discussion of the research into the prediction of height, including a brief description of FDP prediction models for other EVCs. Lastly, conclusions and several recommendations for future directions will be given. 3 2. Research into forensic DNA phenotyping As mentioned in chapter 1, FDP is the process of predicting EVCs of a donor from his or her DNA. EVCs are considered complex traits, their phenotype influenced by multiple genetic loci and environmental factors3,13. This makes it harder to identify the genetic loci of EVCs and thus to predict the phenotypes compared to Mendelian inherited traits, which only have a genetic factor13. Understandably, FDP starts with thoroughly characterising the genotype-phenotype relations of an EVC. This chapter will discuss the most deployed research methods to unravel these relations, as well as an approach to develop and validate a prediction model for forensic practice. Several legal and ethical considerations of FDP are discussed as well, as those are important in the implementation of FDP in practice. 2.1 Research methods for genotype-phenotype relations Genotype-phenotype relations, where single nucleotide polymorphisms (SNPs) are linked to a phenotypic characteristic2,14, are fundamental to FDP. For example, a particular nucleotide at a SNP location is observed more in individuals with blue eyes while another nucleotide at that location is observed in individuals with brown eyes. Genotyping this SNP, together with several other SNPs that are associated with eye colour, can be used to predict the eye colour of an individual. As EVCs are complex traits, there are many SNPs associated with an EVC, their combination determining the phenotype. There are several research methods for investigating genotype-phenotype relations, Table 1 provides a comparative overview of these methods. One of the most used methods to study these genotype-phenotype relations is genome-wide association studies (GWAS)2,12,15. Many thousands of participants are genotyped with SNP arrays and their phenotypes are recorded. Depending on the study, these phenotypes can be diseases, EVCs or both; usually, multiple phenotypes are recorded and investigated in one study. Participants are grouped and compared to find SNPs that significantly differ between a group with a certain variant of a trait and a group with another variant of that trait2,16. There are several aspects of GWAS that need to be considered as they influence the findings. The first aspect is the selection of participants; more and more GWAS are using population-based approaches to participant selection, called cohort studies2.
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