Genetic determinants of freckle occurrence in the Spanish population: Towards ephelides prediction from human DNA samples.
Prediction of human pigmentation traits, one of the most differentiable externally visible characteristics among individuals, from biological samples represents a useful tool in the field of forensic DNA phenotyping. In spite of freckling being a relatively common pigmentation characteristic in Europeans, little is known about the genetic basis of this largely genetically determined phenotype in southern European populations. In this work, we explored the predictive capacity of eight freckle and sunlight sensitivity-related genes in 458 individuals (266 non-freckled controls and 192 freckled cases) from Spain. Four loci were associated with freckling (MC1R, IRF4, ASIP and BNC2), and female sex was also found to be a predictive factor for having a freckling phenotype in our population. After identifying the most informative genetic variants responsible for human ephelides occurrence in our sample set, we developed a DNA-based freckle prediction model using a multivariate regression approach. Once developed, the capabilities of the prediction model were tested by a repeated 10-fold cross-validation approach. The proportion of correctly predicted individuals using the DNA-based freckle prediction model was 74.13%. The implementation of sex into the DNA-based freckle prediction model slightly improved the overall prediction accuracy by 2.19% (76.32%). Further evaluation of the newly-generated prediction model was performed by assessing the model's performance in a new cohort of 212 Spanish individuals, reaching a classification success rate of 74.61%. Validation of this prediction model may be carried out in larger populations, including samples from different European populations. Further research to validate and improve this newly-generated freckle prediction model will be needed before its forensic application. Together with DNA tests already validated for eye and hair colour prediction, this freckle prediction model may lead to a substantially more detailed physical description of unknown individuals from DNA found at the crime scene.
['Hernando|Barbara|B|', 'Ibañez|Maria Victoria|MV|', 'Deserio-Cuesta|Julio Alberto|JA|', 'Soria-Navarro|Raquel|R|', 'Vilar-Sastre|Inca|I|', 'Martinez-Cadenas|Conrado|C|']
D054366:Agouti Signaling Protein D016022:Case-Control Studies D004268:DNA-Binding Proteins D005260:Female D005787:Gene Frequency D005828:Genetics, Population D006801:Humans D050835:Interferon Regulatory Factors D008297:Male D008548:Melanosis D008957:Models, Genetic D015999:Multivariate Analysis D009154:Mutation D011110:Polymorphism, Genetic D044102:Receptor, Melanocortin, Type 1 D012680:Sensitivity and Specificity D012737:Sex Factors D013030:Spain
Freckles Ephelides DNA-based prediction Externally visible traits Forensic science