Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | http://tede2.pucrs.br/tede2/handle/tede/5997 |
Resumo: | 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. |
id |
P_RS_bd47a31045bded8094fc8608f68fa097 |
---|---|
oai_identifier_str |
oai:tede2.pucrs.br:tede/5997 |
network_acronym_str |
P_RS |
network_name_str |
Biblioteca Digital de Teses e Dissertações da PUC_RS |
repository_id_str |
|
spelling |
Alho, Clarice Sampaio509.556.750-49http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782703D1910.679.280-49http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705806U6Rodenbusch, Rodrigo2015-05-14T11:12:13Z2014-08-27http://tede2.pucrs.br/tede2/handle/tede/5997The 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 compreensão da função e expressão dos genes envolvidos nos traços externamente visíveis (EVC; do inglês externally visible characteristics) têm sido amplamente utilizada em vários estudos de evolução humana e investigações forenses. Para este último propósito, vários esforços têm sido feitos para descobrir um modelo eficiente e fácil para a predição da cor da pele e dos olhos em seres humanos. A vantagem óbvia da predição de tais EVCs, através da utilização do DNA, é sua incorporação na rotina em laboratórios forenses, sendo assim aplicada em investigações policiais. Em nosso estudo, relacionamos o genótipo de oito SNPs em genes relacionados com a pigmentação (rs4778138 - OCA2; rs12913832 - HERC2; rs16891982 - SLC45A2; rs8045560 - MC1R; rs1426654 - SLC24A5; rs2733832 - TYRP1; rs1042602 - TYR; rs916977 - HERC2) com diferentes abordagens analíticas. Este painel de SNPs considerou as frequências alélicas obtidas de dados do HapMap e Alfred a partir de indivíduos com Alto Conteúdo de Melanina (HMC; do inglês High Melanin Content; a partir de populações africanas), e Baixo Conteúdo de Melanina (LMC; do inglês Low Melanin Content; a partir de populações europeias) e definiu os alelos H (para predizer os HMC) e alelos L (para predizer os LMC). A distribuição cumulativa dos alelos H e L nos dois grupos com características de pigmentação fenotipicamente distintas, dos 134 indivíduos da nossa população, mostrou que 82% dos indivíduos HMC (N = 61) tinham oito ou mais alelos H e 100% dos indivíduos de LMC (N = 73) tinham menos de oito alelo H, com o valor de precisão de 96,3%. Outras abordagens como AUC (do inglês; Area Under the Receiver Operating Characteristic Curve), cálculo de PGL (do inglês; Pathway Genetic Load) e GP (do inglês; Genetic Probability) foram realizadas. A análise AUC foi de 0,99 tanto para a predição fenotípica dos HMC quanto LMC; as análises PGL, para o painel com 8 SNPs, teve 93% de concordância genótipo-fenótipo nos HMC ou LMC; e a abordagem GP mostrou 91% de concordância para predição dos fenótipos HMC e LMC. Nossa tecnologia de genotipagem de alto rendimento, combinada com diferentes abordagens analíticas, chegou a uma precisão muito alta para predizer os fenótipos extremos de pigmentação humana. Acreditamos que esta técnica de fenotipagem forense pelo DNA (FDP; do inglês forensic DNA phenotyping), seria particularmente útil nos casos em que os perfis genéticos de locais de crime não fossem encontrados no bancos de dados de DNA ou para ajudar a classificar cadáveres degradados, esqueletos, ou vestígios biológicos de pessoas desaparecidas.Submitted by Setor de Tratamento da Informação - BC/PUCRS (tede2@pucrs.br) on 2015-05-14T11:12:13Z No. of bitstreams: 1 468517 - Texto Completo.pdf: 6892081 bytes, checksum: c5aa659f71c5093d831d4810c3ab482c (MD5)Made available in DSpace on 2015-05-14T11:12:13Z (GMT). No. of bitstreams: 1 468517 - Texto Completo.pdf: 6892081 bytes, checksum: c5aa659f71c5093d831d4810c3ab482c (MD5) Previous issue date: 2014-08-27application/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/162751/468517%20-%20Texto%20Completo.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Biologia Celular e MolecularPUCRSBrasilFaculdade de BiociênciasBIOLOGIA CELULARBIOLOGIA MOLECULARGENÉTICA MOLECULARDNACIENCIAS BIOLOGICAS::BIOLOGIA GERALAnálise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melaninainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis819824693009663736060060060036528317262667714-1634559385931244697info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAIL468517 - Texto Completo.pdf.jpg468517 - Texto Completo.pdf.jpgimage/jpeg3142http://tede2.pucrs.br/tede2/bitstream/tede/5997/4/468517+-+Texto+Completo.pdf.jpgba5d201d432e3531d4a46b8f821fde84MD54TEXT468517 - Texto Completo.pdf.txt468517 - Texto Completo.pdf.txttext/plain136788http://tede2.pucrs.br/tede2/bitstream/tede/5997/3/468517+-+Texto+Completo.pdf.txt77be005fa06ef9f22619fec88f4d7cb6MD53ORIGINAL468517 - Texto Completo.pdf468517 - Texto Completo.pdfapplication/pdf6892081http://tede2.pucrs.br/tede2/bitstream/tede/5997/2/468517+-+Texto+Completo.pdfc5aa659f71c5093d831d4810c3ab482cMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8610http://tede2.pucrs.br/tede2/bitstream/tede/5997/1/license.txt5a9d6006225b368ef605ba16b4f6d1beMD51tede/59972015-09-29 08:21:56.103oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2015-09-29T11:21:56Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
title |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
spellingShingle |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina Rodenbusch, Rodrigo BIOLOGIA CELULAR BIOLOGIA MOLECULAR GENÉTICA MOLECULAR DNA CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
title_full |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
title_fullStr |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
title_full_unstemmed |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
title_sort |
Análise de SNPS em genes de pigmentação humana em indivíduos com alto ou baixo conteúdo de melanina |
author |
Rodenbusch, Rodrigo |
author_facet |
Rodenbusch, Rodrigo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Alho, Clarice Sampaio |
dc.contributor.advisor1ID.fl_str_mv |
509.556.750-49 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782703D1 |
dc.contributor.authorID.fl_str_mv |
910.679.280-49 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705806U6 |
dc.contributor.author.fl_str_mv |
Rodenbusch, Rodrigo |
contributor_str_mv |
Alho, Clarice Sampaio |
dc.subject.por.fl_str_mv |
BIOLOGIA CELULAR BIOLOGIA MOLECULAR GENÉTICA MOLECULAR DNA |
topic |
BIOLOGIA CELULAR BIOLOGIA MOLECULAR GENÉTICA MOLECULAR DNA CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
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. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-08-27 |
dc.date.accessioned.fl_str_mv |
2015-05-14T11:12:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://tede2.pucrs.br/tede2/handle/tede/5997 |
url |
http://tede2.pucrs.br/tede2/handle/tede/5997 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
8198246930096637360 |
dc.relation.confidence.fl_str_mv |
600 600 600 |
dc.relation.department.fl_str_mv |
36528317262667714 |
dc.relation.cnpq.fl_str_mv |
-1634559385931244697 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Pontifícia Universidade Católica do Rio Grande do Sul |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Biologia Celular e Molecular |
dc.publisher.initials.fl_str_mv |
PUCRS |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade de Biociências |
publisher.none.fl_str_mv |
Pontifícia Universidade Católica do Rio Grande do Sul |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) instacron:PUC_RS |
instname_str |
Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
instacron_str |
PUC_RS |
institution |
PUC_RS |
reponame_str |
Biblioteca Digital de Teses e Dissertações da PUC_RS |
collection |
Biblioteca Digital de Teses e Dissertações da PUC_RS |
bitstream.url.fl_str_mv |
http://tede2.pucrs.br/tede2/bitstream/tede/5997/4/468517+-+Texto+Completo.pdf.jpg http://tede2.pucrs.br/tede2/bitstream/tede/5997/3/468517+-+Texto+Completo.pdf.txt http://tede2.pucrs.br/tede2/bitstream/tede/5997/2/468517+-+Texto+Completo.pdf http://tede2.pucrs.br/tede2/bitstream/tede/5997/1/license.txt |
bitstream.checksum.fl_str_mv |
ba5d201d432e3531d4a46b8f821fde84 77be005fa06ef9f22619fec88f4d7cb6 c5aa659f71c5093d831d4810c3ab482c 5a9d6006225b368ef605ba16b4f6d1be |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
repository.mail.fl_str_mv |
biblioteca.central@pucrs.br|| |
_version_ |
1799765311909527552 |