Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses
Ano de defesa: | 2017 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul
|
Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Biologia Celular e Molecular
|
Departamento: |
Escola de Ci?ncias
|
País: |
Brasil
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.pucrs.br/tede2/handle/tede/7868 |
Resumo: | Genes related to externally visible characteristics (EVC) present a great importance for the prediction of skin and eye colors in humans. In this study, we tested the ability of a set of SNPs in pigment-related genes to predict skin and eye colors in an admixed south Brazilian population. First, we used the Cinderella - Tiana - Snow White model to analyze the allelic distribution of eight biallelic SNPs in pigment-related. Cinderella and Tiana patterns have respectively low and high melanin content in skin and eyes; Cinderella has white skin and blue eyes (low melanin content; LMC) and Tiana has dark skin and eyes (high melanin content; HMC). Comparative investigation between frequencies of genetic variants in Cinderella-Like versus Tiana-Like subjects may indicate which polymorphic variant is associated with melanin synthesis in skin and eyes. Coordinately, studies with Snow White-Like subjects may be informative to reveal any tissue-specific expression, since these individuals have both white skin (LMC) and dark eyes (HMC). Based on allele frequencies of different human popullations, allele ?L? was used for the alleles associated with low melanin content populations (Cinderela-like subjects), and allele ?H? was used for the alleles associated with high melanin content populations (Tiana-like subjects). Allelic distribution of eight SNPs showed that 100% of Cinderella- like subjects (N= 73) had less than eight H alleles, and 82% of Tiana-Like subjects (N= 61) had eight or more H alleles. The AUC (Area Under the Receiver Operating Characteristic Curve) value was 0.99, and the calculation of PGL (Pathway Genetic Load) and GP (Genetic Probability) showed that the SNP set presented 93% and 91% concordance between DNA genotype and phenotypes, respectively. Factorial discriminant analyses (FDA) performed in the Snow White group (light skin and dark eyes; N= 116) showed an association between SNPs rs16891982 (SLC45A2), rs8045560 (MC1R), rs1426654 (SLC24A5), rs2733832 (TYRP1), and rs1042602 (TYR) and the Cinderella cluster for skin phenotype, and an association between SNPS rs4778138 (OCA2), rs12913832 (HERC2), and rs916977 (HERC2) and the Tiana cluster for eye phenotype. Lastly, we studied 436 South Brazilian subjects with different skin and eye colors to construct a multinomial logistic regression model able to predict phenotype. The model was tested in 40 random subjects to measure the efficiency of the prediction. The data presented 93% concordance between the predicted and the observed phenotype, showing the successful phenotype prediction of the model in South Brazilian individuals. This is important since Brazil has an ethnically mixed population in which genomic structure may favor epistatic and pleiotropic effects not observed in populations that are more homogeneous. The analyses presented here are an important contribution to forensic DNA phenotyping scenario. |
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Alho, Clarice Sampaiohttp://lattes.cnpq.br/9777434407315395http://lattes.cnpq.br/4917767756826856Sawitzki, Fernanda Rosa2018-02-26T20:08:29Z2017-11-07http://tede2.pucrs.br/tede2/handle/tede/7868Genes related to externally visible characteristics (EVC) present a great importance for the prediction of skin and eye colors in humans. In this study, we tested the ability of a set of SNPs in pigment-related genes to predict skin and eye colors in an admixed south Brazilian population. First, we used the Cinderella - Tiana - Snow White model to analyze the allelic distribution of eight biallelic SNPs in pigment-related. Cinderella and Tiana patterns have respectively low and high melanin content in skin and eyes; Cinderella has white skin and blue eyes (low melanin content; LMC) and Tiana has dark skin and eyes (high melanin content; HMC). Comparative investigation between frequencies of genetic variants in Cinderella-Like versus Tiana-Like subjects may indicate which polymorphic variant is associated with melanin synthesis in skin and eyes. Coordinately, studies with Snow White-Like subjects may be informative to reveal any tissue-specific expression, since these individuals have both white skin (LMC) and dark eyes (HMC). Based on allele frequencies of different human popullations, allele ?L? was used for the alleles associated with low melanin content populations (Cinderela-like subjects), and allele ?H? was used for the alleles associated with high melanin content populations (Tiana-like subjects). Allelic distribution of eight SNPs showed that 100% of Cinderella- like subjects (N= 73) had less than eight H alleles, and 82% of Tiana-Like subjects (N= 61) had eight or more H alleles. The AUC (Area Under the Receiver Operating Characteristic Curve) value was 0.99, and the calculation of PGL (Pathway Genetic Load) and GP (Genetic Probability) showed that the SNP set presented 93% and 91% concordance between DNA genotype and phenotypes, respectively. Factorial discriminant analyses (FDA) performed in the Snow White group (light skin and dark eyes; N= 116) showed an association between SNPs rs16891982 (SLC45A2), rs8045560 (MC1R), rs1426654 (SLC24A5), rs2733832 (TYRP1), and rs1042602 (TYR) and the Cinderella cluster for skin phenotype, and an association between SNPS rs4778138 (OCA2), rs12913832 (HERC2), and rs916977 (HERC2) and the Tiana cluster for eye phenotype. Lastly, we studied 436 South Brazilian subjects with different skin and eye colors to construct a multinomial logistic regression model able to predict phenotype. The model was tested in 40 random subjects to measure the efficiency of the prediction. The data presented 93% concordance between the predicted and the observed phenotype, showing the successful phenotype prediction of the model in South Brazilian individuals. This is important since Brazil has an ethnically mixed population in which genomic structure may favor epistatic and pleiotropic effects not observed in populations that are more homogeneous. The analyses presented here are an important contribution to forensic DNA phenotyping scenario.Os genes relacionados a caracter?sticas externamente vis?veis (EVC) apresentam grande import?ncia para a previs?o de cores de pele e olho em humanos. Neste estudo, testamos a capacidade de um conjunto de SNPs em genes relacionados ? s?ntese de pigmento melanina para prever cores de pele e olho em uma popula??o sul-brasileira. Inicialmente, utilizamos o modelo Cinderela - Tiana - Neve Branca para analisar a distribui??o al?lica de oito SNPs bial?licos associados ? produ??o da melanina. Os padr?es Cinderela e Tiana possuem respectivamente baixo e alto conte?do de melanina na pele e nos olhos; Cinderela tem pele branca e olhos azuis (baixo conte?do de melanina, LMC) e Tiana tem pele e olhos escuros (alto conte?do de melanina, HMC). A investiga??o comparativa entre frequ?ncias de variantes gen?ticas em indiv?duos com Cinderela-Like versus Tiana-Like pode indicar qual variante polim?rfica est? associada ? s?ntese de melanina na pele e nos olhos. De forma coordenada, os estudos com indiv?duos Branca de Neve-Like podem ser informativos para revelar a express?o tecido-espec?fica, uma vez que esses indiv?duos t?m pele branca (LMC) e olhos escuros (HMC). Com base em frequ?ncias de alelos de diferentes popula??es humanas, o nome alelo "L" foi utilizado para os alelos associados a popula??es de baixo conte?do de melanina (indiv?duos Cinderela-Like) e o nome alelo "H" foi utilizado para os alelos associados a popula??es de alto conte?do de melanina (Indiv?duos Tiana-Like). A distribui??o al?lica de oito SNPs mostrou que 100% de indiv?duos com Cinderela-Like (N= 73) tinham menos de oito alelos H e 82% de indiv?duos Tiana-Like (N= 61) tinham oito ou mais alelos H. O valor AUC (Area Under the Receiver Operating Characteristic Curve) foi de 0,99 e o c?lculo de PGL (Pathway Genetic Load) e GP (Probabilidade Gen?tica) mostrou que o conjunto de SNP apresentou concord?ncia de 93% e 91% entre gen?tipo e fen?tipo, respectivamente. As an?lises discriminantes fatoriais (FDA) realizadas no grupo Branca de Neve-Like (pele clara e olhos escuros; N= 116) mostraram associa??o positiva entre SNPs rs16891982 (SLC45A2), rs8045560 (MC1R), rs1426654 (SLC24A5), rs2733832 (TYRP1) e rs1042602 (TYR) e o cluster de Cinderela para o fen?tipo da pele, e associa??o positiva entre SNPS rs4778138 (OCA2), rs12913832 (HERC2) e rs916977 (HERC2) e o cluster Tiana para o fen?tipo dos olhos. Por fim, estudamos 436 sujeitos sul-brasileiros com diferentes cores de pele e de olhos para construir um modelo de regress?o log?stica multinomial capaz de prever o fen?tipo. O modelo foi testado em 40 indiv?duos aleat?rios para medir a efici?ncia da predi??o. Os dados apresentaram concord?ncia de 93% entre o fen?tipo previsto e observado, mostrando a previs?o fenot?pica bem-sucedida do modelo em indiv?duos sul-brasileiros. Isso ? importante, uma vez que o Brasil tem uma popula??o etnicamente mista, na qual a estrutura gen?mica pode favorecer os efeitos epistaticos e pleiotr?picos n?o observados em popula??es mais homog?neas. As an?lises aqui apresentadas s?o uma importante contribui??o para a ?rea da fenotipagem por DNA.Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2018-02-26T11:20:29Z No. of bitstreams: 1 FERNANDA_ROSA_SAWITSKI_TES.pdf: 5519043 bytes, checksum: d8234f6f341fd9d5f2c4a39db88b714c (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-02-26T20:03:16Z (GMT) No. of bitstreams: 1 FERNANDA_ROSA_SAWITSKI_TES.pdf: 5519043 bytes, checksum: d8234f6f341fd9d5f2c4a39db88b714c (MD5)Made available in DSpace on 2018-02-26T20:08:29Z (GMT). No. of bitstreams: 1 FERNANDA_ROSA_SAWITSKI_TES.pdf: 5519043 bytes, checksum: d8234f6f341fd9d5f2c4a39db88b714c (MD5) Previous issue date: 2017-11-07Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/170976/TES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.jpghttp://tede2.pucrs.br:80/tede2/retrieve/177615/TES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Biologia Celular e MolecularPUCRSBrasilEscola de Ci?nciasForensePigmenta??o HumanaFenotipagemSNPCIENCIAS BIOLOGICAS::BIOLOGIA GERALFenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forensesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho ser? publicado como artigo ou livro24 meses26/02/20208198246930096637360500500600-16345593859312446972075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSORIGINALTES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdfTES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdfapplication/pdf5519043http://tede2.pucrs.br/tede2/bitstream/tede/7868/5/TES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdfd8234f6f341fd9d5f2c4a39db88b714cMD55THUMBNAILTES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.jpgTES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.jpgimage/jpeg4088http://tede2.pucrs.br/tede2/bitstream/tede/7868/4/TES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.jpg325bac94b4bc46c63bde81b9c7264d37MD54TES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.jpgTES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.jpgimage/jpeg5643http://tede2.pucrs.br/tede2/bitstream/tede/7868/7/TES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.jpga3c412de9043622751e968cdcf535a3aMD57TEXTTES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.txtTES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.txttext/plain1753http://tede2.pucrs.br/tede2/bitstream/tede/7868/3/TES_FERNANDA_ROSA_SAWITZKI_CONFIDENCIAL.pdf.txt28a485c182a599ccdc4a186bb7df28beMD53TES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.txtTES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.txttext/plain138222http://tede2.pucrs.br/tede2/bitstream/tede/7868/6/TES_FERNANDA_ROSA_SAWITZKI_COMPLETO.pdf.txte3264eaba5f49283f06b6f613918408fMD56LICENSElicense.txtlicense.txttext/plain; charset=utf-8610http://tede2.pucrs.br/tede2/bitstream/tede/7868/1/license.txt5a9d6006225b368ef605ba16b4f6d1beMD51tede/78682020-02-27 20:01:00.87oai: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:2020-02-27T23:01Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
title |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
spellingShingle |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses Sawitzki, Fernanda Rosa Forense Pigmenta??o Humana Fenotipagem SNP CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
title_full |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
title_fullStr |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
title_full_unstemmed |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
title_sort |
Fenotipagem por DNA - variantes em genes humanos que regulam a pigmenta??o de olhos e de pele : an?lise fenot?pica e genot?pica de indiv?duos sulbrasileiros para fins forenses |
author |
Sawitzki, Fernanda Rosa |
author_facet |
Sawitzki, Fernanda Rosa |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Alho, Clarice Sampaio |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9777434407315395 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4917767756826856 |
dc.contributor.author.fl_str_mv |
Sawitzki, Fernanda Rosa |
contributor_str_mv |
Alho, Clarice Sampaio |
dc.subject.por.fl_str_mv |
Forense Pigmenta??o Humana Fenotipagem SNP |
topic |
Forense Pigmenta??o Humana Fenotipagem SNP CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Genes related to externally visible characteristics (EVC) present a great importance for the prediction of skin and eye colors in humans. In this study, we tested the ability of a set of SNPs in pigment-related genes to predict skin and eye colors in an admixed south Brazilian population. First, we used the Cinderella - Tiana - Snow White model to analyze the allelic distribution of eight biallelic SNPs in pigment-related. Cinderella and Tiana patterns have respectively low and high melanin content in skin and eyes; Cinderella has white skin and blue eyes (low melanin content; LMC) and Tiana has dark skin and eyes (high melanin content; HMC). Comparative investigation between frequencies of genetic variants in Cinderella-Like versus Tiana-Like subjects may indicate which polymorphic variant is associated with melanin synthesis in skin and eyes. Coordinately, studies with Snow White-Like subjects may be informative to reveal any tissue-specific expression, since these individuals have both white skin (LMC) and dark eyes (HMC). Based on allele frequencies of different human popullations, allele ?L? was used for the alleles associated with low melanin content populations (Cinderela-like subjects), and allele ?H? was used for the alleles associated with high melanin content populations (Tiana-like subjects). Allelic distribution of eight SNPs showed that 100% of Cinderella- like subjects (N= 73) had less than eight H alleles, and 82% of Tiana-Like subjects (N= 61) had eight or more H alleles. The AUC (Area Under the Receiver Operating Characteristic Curve) value was 0.99, and the calculation of PGL (Pathway Genetic Load) and GP (Genetic Probability) showed that the SNP set presented 93% and 91% concordance between DNA genotype and phenotypes, respectively. Factorial discriminant analyses (FDA) performed in the Snow White group (light skin and dark eyes; N= 116) showed an association between SNPs rs16891982 (SLC45A2), rs8045560 (MC1R), rs1426654 (SLC24A5), rs2733832 (TYRP1), and rs1042602 (TYR) and the Cinderella cluster for skin phenotype, and an association between SNPS rs4778138 (OCA2), rs12913832 (HERC2), and rs916977 (HERC2) and the Tiana cluster for eye phenotype. Lastly, we studied 436 South Brazilian subjects with different skin and eye colors to construct a multinomial logistic regression model able to predict phenotype. The model was tested in 40 random subjects to measure the efficiency of the prediction. The data presented 93% concordance between the predicted and the observed phenotype, showing the successful phenotype prediction of the model in South Brazilian individuals. This is important since Brazil has an ethnically mixed population in which genomic structure may favor epistatic and pleiotropic effects not observed in populations that are more homogeneous. The analyses presented here are an important contribution to forensic DNA phenotyping scenario. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-11-07 |
dc.date.accessioned.fl_str_mv |
2018-02-26T20:08:29Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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http://tede2.pucrs.br/tede2/handle/tede/7868 |
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http://tede2.pucrs.br/tede2/handle/tede/7868 |
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por |
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por |
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8198246930096637360 |
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2075167498588264571 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
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Programa de P?s-Gradua??o em Biologia Celular e Molecular |
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PUCRS |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Escola de Ci?ncias |
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Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
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