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Data obtained with the use of massive parallel sequencing (MPS) can be valuable in population genetics studies. In particular, such data harbor the potential for distinguishing samples from different populations, especially from those coming from adjacent populations of common origin. Machine learning (ML) techniques seem to be especially well suited for analyzing large datasets obtained using MPS. The Slavic populations constitute about a third of the population of Europe and inhabit a large area of the continent, while being relatively closely related in population genetics terms. In this proof-of-concept study, various ML techniques were used to classify DNA samples from Slavic and non-Slavic individuals. The primary objective of this study was to empirically evaluate the feasibility of discerning the genetic provenance of individuals of Slavic descent who exhibit genetic similarity, with the overarching goal of categorizing DNA specimens derived from diverse Slavic population representatives. Raw sequencing data were pre-processed, to obtain a 1200 character-long binary vector. A total of three classifiers were used—Random Forest, Support Vector Machine (SVM), and XGBoost. The most-promising results were obtained using SVM with a linear kernel, with 99.9% accuracy and F1-scores of 0.9846–1.000 for all classes. [ABSTRACT FROM AUTHOR]

• Custom-built ancestry panel of 111 AIM-SNPs developed for North African and Middle Eastern populations ('NAME' panel). • Independent evaluation and validation in three European member laboratories of the EUROFORGEN consortium. • Maximum differentiation of six major geographical regions obtained with 237 AIM-SNPs (combined NAME and Global AIMs panels). Inference of biogeographic origin is an important factor in clinical, population and forensic genetics. The information provided by AIMs (Ancestry Informative Markers) can allow the differentiation of major continental population groups, and several AIM panels have been developed for this purpose. However, from these major population groups, Eurasia covers a wide area between two continents that is difficult to differentiate genetically. These populations display a gradual genetic cline from West Europe to South Asia in terms of allele frequency distribution. Although differences have been reported between Europe and South Asia, Middle East populations continue to be a target of further investigations due to the lack of genetic variability, therefore hampering their genetic differentiation from neighboring populations. In the present study, a custom-built ancestry panel was developed to analyze North African and Middle Eastern populations, designated the 'NAME' panel. The NAME panel contains 111 SNPs that have patterns of allele frequency differentiation that can distinguish individuals originating in North Africa and the Middle East when combined with a previous set of 126 Global AIM-SNPs. [ABSTRACT FROM AUTHOR]

DNA methylation based age prediction is a new method in the toolbox of forensic genetics. Typically, the method is applied in the course of police investigation e.g. to predict the age of an unknown person that has left a biological trace at a crime scene. The method can also be used to answer other forensic questions, for example to estimate the age of unknown human bodies in the course of the identification process. In the present study, we tested for a potential impact of biogeographic ancestry (BGA) on age predictions using five age dependent methylated CpG sites within the genetic regions of ELOVL2, MIR29B2CHG, FHL2, KLF14 and TRIM59. We collected 102 blood samples each from donors living in Iraq, Middle East (ME) and Germany, Central Europe (EU). Both sample sets were matched in sex and age ranging from 18 to 68 years with exactly one male and female sample per year of age. All samples were analyzed by bisulfite pyrosequencing applying a multiplex pre-amplification strategy based on a single input of 35 ng converted DNA in the PCR. For the CpGs in MIR29B2CHG , FHL2 and KLF14 , we observed significantly different methylation levels between the two populations. While we were able to train two highly accurate prediction models for the respective population with mean absolute deviations between predicted and actual ages (MAD) of 3.34 years for the ME model, and 2.72 years for the EU model, we found an absolute prediction difference between the two population specific models of more than 4 years. A combined model for both populations compensated the methylation difference between the two populations, providing MADs of prediction of only 3.81 years for ME and 3.31 years for EU samples. In total, the results of the present study strongly support the benefit of BGA information for more reliable methylation based age predictions. • Significant methylation differences between EU and ME samples were found for MIR29B2CHG , FHL2 and KLF14. • Population specific CpG methylation caused more than four years prediction differences between EU and ME samples. • Population specific age prediction models lead to great prediction errors when applied to samples with different ancestry. • A combined model compensated for population specific methylation differences but underperformed population specific models. • Biogeographic ancestry has been identified as a relevant co-variable for reliable DNA methylation based age predictions. [ABSTRACT FROM AUTHOR]

Forensic DNA Phenotyping (FDP) comprises the prediction of a person's externally visible characteristics regarding appearance, biogeographic ancestry and age from DNA of crime scene samples, to provide investigative leads to help find unknown perpetrators that cannot be identified with forensic STR-profiling. In recent years, FDP has advanced considerably in all of its three components, which we summarize in this review article. Appearance prediction from DNA has broadened beyond eye, hair and skin color to additionally comprise other traits such as eyebrow color, freckles, hair structure, hair loss in men, and tall stature. Biogeographic ancestry inference from DNA has progressed from continental ancestry to sub-continental ancestry detection and the resolving of co-ancestry patterns in genetically admixed individuals. Age estimation from DNA has widened beyond blood to more somatic tissues such as saliva and bones as well as new markers and tools for semen. Technological progress has allowed forensically suitable DNA technology with largely increased multiplex capacity for the simultaneous analysis of hundreds of DNA predictors with targeted massively parallel sequencing (MPS). Forensically validated MPS-based FDP tools for predicting from crime scene DNA i) several appearance traits, ii) multi-regional ancestry, iii) several appearance traits together with multi-regional ancestry, and iv) age from different tissue types, are already available. Despite recent advances that will likely increase the impact of FDP in criminal casework in the near future, moving reliable appearance, ancestry and age prediction from crime scene DNA to the level of detail and accuracy police investigators may desire, requires further intensified scientific research together with technical developments and forensic validations as well as the necessary funding. • Advances in DNA prediction of appearance, ancestry and age increase impact of Forensic DNA Phenotyping. • Appearance DNA prediction broadened beyond eye, hair, skin color to include more traits. • Ancestry DNA prediction progressed beyond continental levels to sub-regional and admixture resolution. • Age DNA prediction widened beyond blood to more somatic tissues and semen. • FDP tools with improved multiplexing capacity based on massively parallel sequencing are emerging. [ABSTRACT FROM AUTHOR]

Forensic DNA phenotyping (FDP) includes biogeographic ancestry (BGA) inference and externally visible characteristics (EVCs) prediction directly from an evidential DNA sample as alternatives to provide valuable intelligence when conventional DNA profiling fails to achieve identification. In this context, the application of Massively Parallel Sequencing (MPS) methodologies, which enables simultaneous typing of multiple samples and hundreds of forensic markers, has been gradually implemented in forensic genetic casework. The Precision ID Ancestry Panel (Thermo Fisher Scientific, Waltham, USA) is a forensic multiplex assay consisting of 165 autosomal SNPs designed to provide biogeographic ancestry information. In this work, a sample of 250 individuals from Rio Grande do Sul (RS) State, southern Brazil, apportioned into four main population groups (African-, European-, Amerindian-, and Admixed-derived Gauchos), was evaluated with this panel, to assess the feasibility of this approach in a highly heterogeneous population. Forensic descriptive parameters estimated for each population group revealed that this panel has enough polymorphic and informative SNPs to be used as a supplementary instrument in forensic individual identification and kinship testing regardless of ethnicity. No statistically significant deviation from Hardy-Weinberg equilibrium was observed after Bonferroni correction. However, seven loci pairs displayed linkage disequilibrium in pairwise LD testing (p < 3.70 × 10−6). Interpopulation comparisons by F ST analysis, MDS plot, and STRUCTURE analysis among the four RS population groups apart and along with 89 reference worldwide populations demonstrated that Admixed- and African-derived Gauchos present the highest levels of admixture and population stratification, whereas European- and Amerindian-derived exhibit a more homogeneous genetic conformation. • 250 samples from four South Brazilian population groups were typed for 165 AISNPs. • All loci were in HW equilibrium, with association between seven loci pairs. • South Amerindians show greater miscegenation than European-derived Gauchos. • Admixed and African-derived present the highest levels of population stratification. • The panel is a promising tool for biogeographical ancestry and human identification. [ABSTRACT FROM AUTHOR]

Massively parallel sequencing can provide genetic data for hundreds to thousands of loci in a single assay for various types of forensic testing. However, available commercial kits require an initial PCR amplification of short-to-medium sized targets which limits their application for highly degraded DNA. Development and optimisation of large PCR multiplexes also prevents creation of custom panels that target different suites of markers for identity, biogeographic ancestry, phenotype, and lineage markers (Y-chromosome and mtDNA). Hybridisation enrichment, an alternative approach for target enrichment prior to sequencing, uses biotinylated probes to bind to target DNA and has proven successful on degraded and ancient DNA. We developed a customisable hybridisation capture method, that uses individually mixed baits to allow tailored and targeted enrichment to specific forensic questions of interest. To allow collection of forensic intelligence data, we assembled and tested a custom panel of hybridisation baits to infer biogeographic ancestry, hair and eye colour, and paternal lineage (and sex) on modern male and female samples with a range of self-declared ancestries and hair/eye colour combinations. The panel correctly estimated biogeographic ancestry in 9/12 samples (75%) but detected European admixture in three individuals from regions with admixed demographic history. Hair and eye colour were predicted correctly in 83% and 92% of samples respectively, where intermediate eye colour and blond hair were problematic to predict. Analysis of Y-chromosome SNPs correctly assigned sex and paternal haplogroups, the latter complementing and supporting biogeographic ancestry predictions. Overall, we demonstrate the utility of this hybridisation enrichment approach to forensic intelligence testing using a combined suite of biogeographic ancestry, phenotype, and Y-chromosome SNPs for comprehensive biological profiling. • Single nucleotide polymorphisms (SNPs) can provide forensic intelligence. • Existing forensic SNP panels are inflexible and may perform poorly on degraded DNA. • We developed and tested a customisable, SNP hybridisation enrichment panel. • The panel provides valuable biological profiles and forensic intelligence. [ABSTRACT FROM AUTHOR]

Purpose Racial/ethnic disparities in the incidence of type 2 diabetes mellitus (T2DM) are well documented, and many researchers have proposed that biogeographical ancestry (BGA) may play a role in these disparities. However, studies examining the role of BGA on T2DM have produced mixed results to date. Therefore, the objective of this research was to quantify the contribution of BGA to racial/ethnic disparities in T2DM incidence controlling for the mediating influences of socioeconomic factors. Methods We analyzed data from the Boston Area Community Health Survey, a prospective cohort with approximately equal numbers of black, Hispanic, and white participants. We used 63 ancestry-informative markers to calculate the percentages of participants with West African and Native American ancestry. We used logistic regression with G-computation to analyze the contribution of BGA and socioeconomic factors to racial/ethnic disparities in T2DM incidence. Results We found that socioeconomic factors accounted for 44.7% of the total effect of T2DM attributed to black race and 54.9% of the effect attributed to Hispanic ethnicity. We found that BGA had almost no direct association with T2DM and was almost entirely mediated by self-identified race/ethnicity and socioeconomic factors. Conclusions It is likely that nongenetic factors, specifically socioeconomic factors, account for much of the reported racial/ethnic disparities in T2DM incidence. [ABSTRACT FROM AUTHOR]

Skin pigmentation is one of the most prominent and variable phenotypes in humans. We compared the alleles of 163 SNPs and indels from the Human Pigmentation (HuPi) AmpliSeq™ Custom panel, and biogeographic ancestry with the quantitative skin pigmentation levels on the upper arm, lower arm, and forehead of 299 Pakistani individuals from three subpopulations: Baloch, Pashtun, and Punjabi. The biogeographic ancestry of each individual was estimated using the Precision ID Ancestry Panel. All individuals were mainly of mixed South-Central Asian and European ancestry. However, the Baloch individuals also had an average proportion of Sub-Saharan African ancestry of approximately 10%, whereas it was <1% in the Punjabi and Pashtun individuals. The pairwise genetic distances between the Pashtun, Punjabi, and Baloch subpopulations based on the ancestry markers were statistically significantly different. Individuals from the Pashtun subpopulation had statistically significantly lower skin pigmentation than individuals from the Punjabi and Baloch subpopulations (p < 0.05). The proportions of European and Sub-Saharan African ancestry and five SNPs (rs1042602, rs10831496, rs1426654, rs16891982, and rs12913832) were statistically significantly associated with skin pigmentation at either the upper arm, lower arm or forehead in the Pakistani population after correction for multiple testing (p < 10−3). A model based on four of these SNPs (rs1426654, rs1042602, rs16891982, and rs12913832) explained 33% of the upper arm skin pigmentation. The four SNPs and the proportions of European and Sub-Saharan African ancestry explained 37% of the upper arm skin pigmentation. Our results indicate that the four likely causative SNPs, rs1426654, rs1042602, rs16891982, and rs12913832 located in SLC24A5, TYR, SLC45A2, and HERC2, respectively, are essential for skin color variation in the admixed Pakistani subpopulations. [ABSTRACT FROM AUTHOR]

In 1932, seven burials were discovered on a Texas plantation that was originally the site of a 17th-century Caddo Indian village. Of the seven excavated graves, one set of remains (an adult male) was notably buried in a manner inconsistent with traditional Caddoan burial practices and has long been purported to be the remains of Sieur de Marle (a member of the French explorer La Salle's last expedition). Diary accounts of La Salle's expedition scribe report that Sieur de Marle died along a river near an Indian village during a trek to Canada to find help for colonists left behind at the ill-fated Fort St. Louis. Additionally, two lead projectiles recovered from the grave were ballistically analyzed and determined to be consistent with ammunition used in 17th-century weaponry. In the 1980s, anthropologists requested access to the remains for study, but the skull was missing. Cranial measurements recorded in 1940 and 1962 (by two independent anthropologists) were used to investigate the ancestry of this individual; and the Giles-Elliot (G-E) discriminant function was calculated to be 18.1, within the Anglo-European range. Dietary isotope testing on non-cranial skeletal elements determined that this unknown male's diet was rich in animal/marine protein sources, which differs appreciably from Caddo Indian populations of that time period. In order to genetically assess this individual's biogeographic ancestry and to provide further support that this individual is of European descent, mitochondrial DNA (mtDNA) sequencing was performed using the Applied Biosystems™ Precision ID mtDNA Whole Genome Panel. mtDNA sequencing of multiple sections from two different long bones yielded compiled results consistent with either Haplogroup H or R, both predominantly European mtDNA haplogroups. Further anthropological calculations were conducted using cranial measurements, FORDISC™ software, and discriminant function analysis. Two-way, four-way, and multigroup discriminant function analyses further classify this set of unidentified remains as being White (European) in origin, with posterior probabilities of 0.999, 0.881 and 0.986, respectively. Combined with historical records of Sieur de Marle's death, as well as overlays of historical and contemporary maps which demonstrate that the plantation site aligns with Joutel's diary accounts of de Marle's burial, these collective results support that these remains are of a European male and may possibly belong to this prominent member of La Salle's expedition team. [ABSTRACT FROM AUTHOR]