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A Prospective Screening of Gene Copy Number Variation in Brazilian

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A Prospective Screening of Gene Copy Number Variation in Brazilian Pró-Reitoria Acadêmica Curso de Biomedicina Trabalho de Conclusão de Curso VARIAÇÃO DE GENES DE CÓPIAS MÚLTIPLAS EM POPULAÇÕES MUNDIAIS EM UMA AMOSTRA MISCIGENADA DA POPULAÇÃO BRASILEIRA Autora: Priscilla Orosco Taveira Orientador: Dr. Tulio Cesar de Lima Lins Brasília - DF 2015 1 PRISCILLA OROSCO TAVEIRA VARIAÇÃO DE GENES DE CÓPIAS MÚLTIPLAS EM POPULAÇÕES MUNDIAIS EM UMA AMOSTRA MISCIGENADA DA POPULAÇÃO BRASILEIRA Artigo apresentado ao curso de graduação em Biomedicina da Universidade Católica de Brasília como requisito parcial para obtenção do título de Bacharel em Biomedicina. Orientador: Dr. Tulio Cesar de Lima Lins Brasília 2015 2 Artigo de TCC II, de autoria Priscilla Orosco Taveira, intitulado “VARIAÇÃO DE GENES DE CÓPIAS MÚLTIPLAS EM POPULAÇÕES MUNDIAISEM UMA AMOSTRA MISCIGENADA DA POPULAÇÃO BRASILEIRA”, apresentado como requisito parcial para a obtenção do grau de Bacharel em Biomedicina da Universidade Católica de Brasília, em 24 de Setembro de 2015, defendida e aprovada pela banca examinadora abaixo assinada: ____________________________________________________ Orientador Dr. Tulio Cesar de Lima Lins Pós - doutorando em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília _____________________________________________________ Prof. Dra. Rosangela Vieira de Andrade Curso de Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília _____________________________________________________ Prof. Dra. Marcela Aparecida Chiabai Pós- doutoranda em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília BRASÍLIA 2015 3 Resumo As variantes do número de cópias (CNVs) representam um recurso importante de variação no genoma humano. Alguns genes envolvidos por CNVs são distribuídos de forma diferente entre os grupos de população humana entretanto é importante compreender a distribuição de CNV dentro e entre as populações especialmente naquelas com ascendência miscigenada, tais como as populações brasileiras. O objetivo do estudo foi investigar a variabilidade de um conjunto de CNVs incorporados a genes numa amostra da população brasileira. Os mesmos foram escolhidos com base em dados que mostram que eles possuem uma distribuição diferenciada na variação de cópia entre Africanos e Europeus. Quatro genes (POLRJ4, PCDHB13, NPEPPS e AMY1) foram investigados por qPCR em uma amostra de 96 brasileiros, previamente classificados por ascendência genética. O gene AMY1apresentou um número de cópias variáveis na gama de 1 a 8 cópias, em quanto que o NPEPPS variou de 1 a 5 cópias. A baixa variabilidade foi identificada pelos genes POLRJ4 e PCDHB13, mostrando duas cópias em frequência de 0,875 e 0,917, respectivamente. A ascendência genética não se correlacionou com o número de cópias dos genes AMY1 e NPEPPS. Os resultados proporcionaram uma visão ampla da frequência correspondente a variação do número de cópias do gene em uma amostra da população brasileira, atuando como referência para posteriores estudos genéticos da população o qual pode correlacionar esses polimorfismos com outras características fenotípicas. 4 Anexo 1. Artigo científico: A Prospective Screening of Gene Coy Number Variation in Brazilian Admixed Population Sample Autores: Dianny Elizabeth Jimenez, Tulio Cesar de Lima Lins, Priscilla Orosco Taveira e Rinaldo Wellerson Pereira Revista: Hereditary Genetics. Volume 3, Issue 1, p. 125. 31 Jan, 2014. ISSN:2161-1041. doi:10.4172/2161-1041.1000125 Jimenez et al., Hereditary Genet 2014, 3:1 Hereditary Genetics http://dx.doi.org/10.4172/2161-1041.1000125 Research Article Open Access A Prospective Screening of Gene Copy Number Variation in Brazilian Admixed Population Sample Dianny Elizabeth Jimenez¹, Tulio Cesar de Lima Lins², Priscilla Orosco Taveira¹, Rinaldo Wellerson Pereira¹,²* 1Programa de Pos-Graduaçao em Ciencias Genomicas e Biotecnologia, Universidade Catolica de Brasilia, Brasilia, DF, Brazil 2Programa de Pos-Graduacao em Patologia Molecular, Universidade de Brasilia, Brasilia, DF, Brazil Abstract Copy number variants (CNVs) represent an important source of variation in the human genome. Some CNVS embedded genes are differently distributed among the human population groups. Therefore, it is important to understand the distribution of CNV within and between populations, especially in those with admixed ancestry, such as the Brazilians. The aim of the study was to investigate the variability of a set of CNV-embedded genes in a sample of the Brazilian population. The CNV-embedded genes were chosen based on data showing that they have differential copy variation distribution between African and Europeans. Four genes (POLR2J4, PCDHB13, NPEPPS and AMY1) were investigated by qPCR in a sample of 96 Brazilians, previously classified by genetic ancestry. The gene AMY1 showed a variable copy numbers in the range of 1 to 8 copies whereas NPEPPS ranged from 1 to 5 copies. A low variability was identified for the POLR2J4 and PCDHB13 genes, showing 2 copies in frequency of 0.875 and 0.917, respectively. Genetic ancestry was not correlated to the number of copies of the AMY1and NPEPPS genes. The results provided an overview of the corresponding frequency of gene copy number variation in a sample of the Brazilian population, serving as reference for further genetic population studies, which may correlate these polymorphisms with other phenotypic features. Keywords: qPCR; CNV; POLR2J4; PCDHB13; NPEPPS; AMY1 Material and Methods Introduction Samples Copy number variations (CNVs) are deletions or duplications of The study analyzed DNA samples from 96 (51 men and 45 DNA segments of at least 1000 bases (1 kb) up to several Mb in size women) unrelated Brazilians. The European, African and Native present in a variable range of copy numbers when compared to a American genetic ancestry proportions were previously estimated reference genome [1-4]. Their occurrence is variable among human in the sample with 28 ancestry informative markers [28]. DNA from populations, making them a wide source of population differentiation peripheral blood was extracted by a saline precipitation method, and [5-7]. Copy number polymorphisms (CNPs) are CNVs with population the concentration and quality were determined with NanoDrop® ND-1000 Spectrophotometer (Thermo Scientific, USA). A unique frequencies of at least 1% [8-12]. sample with a high quantity DNA was selected as a calibrator sample CNVs play an important role over several genetic diseases for quality control in all qPCR reactions. All samples were taken with susceptibility, such as obesity, diabetes, cancer and neuropsychiatric the knowledge and consent of the donors, and the Ethic Committee of diseases [7,11-14]. In addition, the genetic heritability of non- Universidade Catolica de Brasilia approved the research protocol. pathological human traits can also be explained by CNVs [15-18]. For Copy number polymorphism estimation instance, adaptive evolution on chemosensation and immune response [19]. Patterns of copy number in salivary amylase gene have also a The four selected genes (AMY1, NPEPPS, PCDH-BETA13 and correlation with human populations with different dietary history, POLR2J4) are within CNV regions that were recognized as polymorphic, revealing an evolutionary selection for copy numbers in cultures with and their copy numbers were differently distributed in representative higher starch diets [20]. Thus, CNV may have exerted an important role populations of European, African and Asian ancestry in a previous in the evolution of physiological adaptations modeling the stratification study [7] and structural variants were accessed in the Database of of continental populations [2]. The literature describes CNVs loci Genomic Variants (DGV, http://dgv.tcag.ca/). showing significant copy number differences between different ethnic Custom TaqMan® copy numbers assays were acquired from Applied groups [14,21-24], including some that are population-specific [25,26]. Biosystems®/Life Technologies® (Table 1). As an endogenous control, a region with a known number of two copies in a human diploid genome, The use of Ancestry-Informative markers (SNPs and Indels polymorphism) has long been used to evaluate population stratification and admixture. It has been used to depict the Brazilian population as one of high heterogeneity, characterized by varying admixture from *Corresponding author: Rinaldo Wellerson Pereira, SGAN 916 Modulo B, “Bloco parental populations, such as European, African and Native Americans C” 2º Andar, Sala C-207 – Brasilia–DF, Brazil, CEP 70790-160, Tel: +55-61-3448- [27-29]. However, studies conducted in the Brazilian population 7222; Fax: +55-61-3347-4797; E-mail: [email protected] evaluated CNV only as a source of pathological variation and, up to Received December 26, 2013; Accepted January 29, 2014; Published January the moment, no investigation considered general population samples 31, 2014 as a source of phenotypic variation, especially relating CNVs and Citation: Jimenez DE, de Lima Lins TC, Taveira PO, Pereira RW (2014) A genetic ancestry. In order to determine the polymorphism degree in Prospective Screening of Gene Copy Number Variation in Brazilian Admixed individuals from the Brazilian population, this study aimed to assess Population Sample. Hereditary Genet 3: 125. doi:10.4172/2161-1041.1000125 the copy number of the CNVs embedded genes AMY1, NPEPPS, Copyright: © 2014 Jimenez DE, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits PCDHB13
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