DNA-based predictive models for the presence of freckles

Abstract

Freckles or ephelides are hyperpigmented spots observed on skin surface mainly in European and Asian populations. Easy recognition and external visibility make prediction of ephelides, the potentially useful target in the field of forensic DNA phenotyping. Prediction of freckles would be a step forward in sketching the physical appearance of unknown perpetrators or decomposed cadavers for the forensic DNA intelligence purposes. Freckles are especially common in people with pale skin and red hair and therefore it is expected that predisposition to freckles may partially share the genetic background with other pigmentation traits. The first proposed freckle prediction model was developed based on investigation that involved variation of MC1R and 8 SNPs from 7 genes in a Spanish cohort [19]. In this study we examined 113 DNA variants from 46 genes previously associated with human pigmentation traits and assessed their impact on freckles presence in a group of 960 individuals from Poland. Nineteen DNA variants revealed associations with the freckle phenotype and the study also revealed that females have ∼1.8 higher odds of freckles presence comparing to males (pvalue = 9.5 × 10 −5 ). Two alternative prediction models were developed using regression methods. A simplified binomial 12-variable model predicts the presence of ephelides with cross-validated AUC = 0.752. A multinomial 14-variable model predicts one of three categoriesnon-freckled, medium freckled and heavily freckled. The two extreme categories, non-freckled and heavily freckled were predicted with moderately high accuracy of cross-validated AUC = 0.754 and 0.792, respectively. Prediction accuracy of the intermediate category was lower, AUC = 0.657. The study presents novel DNA models for prediction of freckles that can be used in forensic investigations and emphasizes significance of pigmentation genes and sex in predictive DNA analysis of freckles. comparing to the adjacent skin areas [2]. Typically, ephelides appear in childhood, suggesting mainly genetic determination of their appearance. Although the number of freckles can increase in adolescence, they may also disappear with age [1,2]. Several genes have already been associated with the presence of freckles and the previous reports clearly show that ephelides-associated loci partially overlap with other pigmentation traits [3][4][5] and skin cancers [6][7][8][9].Ephelides represent important target for the emerging field of forensic DNA phenotyping (FDP). As with the other pigmentation traits

Evaluation of the VISAGE Basic Tool for Appearance and Ancestry Prediction Using PowerSeq Chemistry on the MiSeq FGx System

“…FDP can provide investigative leads, when standard DNA identification is not possible, for example, due to the lack of a suspect’s reference sample or a lack of matches in National DNA Databases [ 3 , 4 ]. Recent studies focused on fine-tuning the selection of DNA markers to predict physical appearance, e.g., [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. The most successful studies developed models for eye, hair and skin color with promising prediction performance analyzing only a few dozen single nucleotide polymorphisms (SNPs) [ 12 , 13 , 14 ].…”

Evaluation of the Ion AmpliSeq™ PhenoTrivium Panel: MPS-Based Assay for Ancestry and Phenotype Predictions Challenged by Casework Samples

“…Forensic genetics currently stands in front of a new era of DNA analysis as Massively Parallel Sequencing (MPS) is becoming a more commonly used tool for DNA analysis. The enhanced multiplexing capabilities of MPS technology coupled with the ability to analyze a variety of marker types has led to increased research and use of single nucleotide polymorphisms (SNPs) to predict externally visible characteristics (EVCs) and biogeographical ancestry (BGA) from a DNA sample [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. To implement the new capabilities in DNA testing, legal changes are obligatory for SNP analysis by MPS to be applied in new cases.…”

Testing the impact of trait prevalence priors in Bayesian-based genetic prediction modeling of human appearance traits

“…Thus far, for eye, hair and skin color various underlying genes have been identified, predictive DNA markers have been identified, DNA tests suitable for analyzing such genetic markers in forensic DNA samples and statistical prediction models have been developed [4][5][6][7][8][9][10], and some of these DNA test systems have been forensically validated [9,11,12]. For traits such as freckles and hair structure, some associated genetic markers and the first predictive models have already been published, respectively [13][14][15][16]; however, no forensically validated tool has been established so far. Prediction models for some other EVCs are currently under investigation [17][18][19][20].…”

“…Here, we assess the impact of incorporating prior knowledge on EVC trait prevalence in a Bayesian setting on improving the accuracy of DNAbased EVC prediction, but also potential pitfalls caused by misspecification of such prior probabilities. To this end, we consider EVCs such as eye, hair and skin color for which prior-free genetic prediction models have previously been established [9,11,12], but also traits such as hair structure and freckles for which the first prediction models were recently proposed without considering priors [13,15,16]. Given the sparsity or even lack of spatial or population-specific prevalence information available for each of these EVCs [24], we investigated the impact of prevalence-informed priors across a grid in the complete space of all possible values for each trait category, thereby emulating the (mis-) specification of the informative prior values.…”