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Previous issue date: 2014-08-27 / The understanding of gene function in the externally visible characteristcs (EVC) expression has several uses in human population evolution studies or in forensic investigations. To this last, some effort has been done to discover an efficient and easy model for prediction of skin and eye color in humans. The obvious advantage of the prediction of such EVCs through the use of DNA is to be incorporated as routine in forensic labs and to be applied to police investigations. In our study we combined the genotyping of eight SNPs in pigment-related genes (rs4778138 - OCA2; rs12913832 - HERC2; rs16891982 - SLC45A2; rs8045560 - MC1R; rs1426654 - SLC24A5; rs2733832 - TYRP1; rs1042602 - TYR; rs916977 - HERC2) with different analytical approaches. Considering this SNP panel we evaluated allele frequencies from HAPMAP and ALFRED data obtained from subjects with High Melanin Content (HMC; from African populations), and Low Melanin Content (LMC; from European populations) and defined the alleles H (to predict HMC subjects) and alleles L (to predict LMC subjects). The cumulative distribution of alleles H and alleles L in two phenotypically different color groups of 134 South Brazilian subjects showed that 82% of HMC subjects (N = 61) had eight or more allele H and 100% of LMC subjects (N = 73) had less than eight allele H, with accuracy value of 96.3%. We performed other analyses using AUC (Area Under the Receiver Operating Characteristic Curve), PGL (Calculation of Pathway Genetic Load), and GP (Genetic Probability) approaches. The AUC was 0.99 in predicting both HMC and LMC phenotypes; PGL showed the eight SNPs panel had 93% of concordance between genotype and HMC or LMC phenotypes; and GP approach showed 91% of concordance between prediction and HMC or LMC phenotypes. Our high-throughput genotyping technology combined with different analytical approaches reached very high accuracy to predict the extreme phenotypes of human pigmentation. We believe this forensic DNA phenotyping (FDP) technique would be particularly useful in cases in which the genetic profiles of crime scenes were not found in the DNA data banks or to help classify degraded cadavers skeletons, or biological clues of dismissed people. / A compreens?o da fun??o e express?o dos genes envolvidos nos tra?os externamente vis?veis (EVC; do ingl?s externally visible characteristics) t?m sido amplamente utilizada em v?rios estudos de evolu??o humana e investiga??es forenses. Para este ?ltimo prop?sito, v?rios esfor?os t?m sido feitos para descobrir um modelo eficiente e f?cil para a predi??o da cor da pele e dos olhos em seres humanos. A vantagem ?bvia da predi??o de tais EVCs, atrav?s da utiliza??o do DNA, ? sua incorpora??o na rotina em laborat?rios forenses, sendo assim aplicada em investiga??es policiais. Em nosso estudo, relacionamos o gen?tipo de oito SNPs em genes relacionados com a pigmenta??o (rs4778138 - OCA2; rs12913832 - HERC2; rs16891982 - SLC45A2; rs8045560 - MC1R; rs1426654 - SLC24A5; rs2733832 - TYRP1; rs1042602 - TYR; rs916977 - HERC2) com diferentes abordagens anal?ticas. Este painel de SNPs considerou as frequ?ncias al?licas obtidas de dados do HapMap e Alfred a partir de indiv?duos com Alto Conte?do de Melanina (HMC; do ingl?s High Melanin Content; a partir de popula??es africanas), e Baixo Conte?do de Melanina (LMC; do ingl?s Low Melanin Content; a partir de popula??es europeias) e definiu os alelos H (para predizer os HMC) e alelos L (para predizer os LMC). A distribui??o cumulativa dos alelos H e L nos dois grupos com caracter?sticas de pigmenta??o fenotipicamente distintas, dos 134 indiv?duos da nossa popula??o, mostrou que 82% dos indiv?duos HMC (N = 61) tinham oito ou mais alelos H e 100% dos indiv?duos de LMC (N = 73) tinham menos de oito alelo H, com o valor de precis?o de 96,3%. Outras abordagens como AUC (do ingl?s; Area Under the Receiver Operating Characteristic Curve), c?lculo de PGL (do ingl?s; Pathway Genetic Load) e GP (do ingl?s; Genetic Probability) foram realizadas. A an?lise AUC foi de 0,99 tanto para a predi??o fenot?pica dos HMC quanto LMC; as an?lises PGL, para o painel com 8 SNPs, teve 93% de concord?ncia gen?tipo-fen?tipo nos HMC ou LMC; e a abordagem GP mostrou 91% de concord?ncia para predi??o dos fen?tipos HMC e LMC. Nossa tecnologia de genotipagem de alto rendimento, combinada com diferentes abordagens anal?ticas, chegou a uma precis?o muito alta para predizer os fen?tipos extremos de pigmenta??o humana. Acreditamos que esta t?cnica de fenotipagem forense pelo DNA (FDP; do ingl?s forensic DNA phenotyping), seria particularmente ?til nos casos em que os perfis gen?ticos de locais de crime n?o fossem encontrados no bancos de dados de DNA ou para ajudar a classificar cad?veres degradados, esqueletos, ou vest?gios biol?gicos de pessoas desaparecidas.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/5997 |
| Date | 27 August 2014 |
| Creators | Rodenbusch, Rodrigo |
| Contributors | Alho, Clarice Sampaio |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biologia Celular e Molecular, PUCRS, Brasil, Faculdade de Bioci?ncias |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 8198246930096637360, 600, 600, 600, 36528317262667714, -1634559385931244697 |
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