RESUMO
The Brazilian population is one of the most heterogeneous populations of the world, formed mainly by an admixture of European, African and Native American populations. Brazil is the fifth largest country in the world (8,511,960 km(2)), being divided into five geographical regions. This study provides population genetic data of up to 137,161 unrelated individuals representing the entire Brazilian territory. Allelic frequencies and other population data analysis are reported for the 15 autosomal STR loci included in the PowerPlex®16 kit (Promega Corporation, Madison, WI, USA). In order to guarantee that individuals were not related, we have considered only F1 data from couples undergoing paternity testing. The number of individuals genotyped for each locus was: CSF1PO (113,526); D3S1358 (135,133); D5S818 (135,181); D7S820 (137,136); D8S1179 (134,211); D13S317 (137,161); D16S539 (136,942); D18S51 (136,739); D21S11 (130,014); FGA (135,839); Penta D (110,333); Penta E (128,055); TH01 (112,695); TPOX (123,102); vWA (127,415). Allele sizes ranged from 1 to 48.2. Statistic parameters (PD, PIC and Ho; considering values ≥0.75) suggest that markers D13S317, D16S539, D18S51, D21S11, D7S820, D8S1179, Penta D, Penta E, TH01, FGA and vWA were more informative for genetic identification purposes in the Brazilian population.
Assuntos
Frequência do Gene , Genética Populacional , Repetições de Microssatélites , Brasil , Impressões Digitais de DNA/métodos , Eletroforese Capilar , Loci Gênicos , Genótipo , Humanos , Reação em Cadeia da PolimeraseRESUMO
INTRODUCTION: Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic variations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated. OBJECTIVE: To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals without the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals. METHODS: The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the 'Time-resolved fluorometer' technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III). RESULTS: The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect against the disease.The DQA1 label proved to be able to differentiate between 71.13% of the diabetic and non-diabetic individuals.This value increased to 82.47% when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups. CONCLUSIONS: The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles.
Assuntos
Antígenos CD/genética , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-D/genética , Insulina/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Alelos , Antígeno CTLA-4 , Estudos de Casos e Controles , Análise Discriminante , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , HumanosRESUMO
INTRODUCTION:Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic variations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated. OBJECTIVE:To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals without the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals. METHODS: The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the "Time-resolved fluorometer" technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III). RESULTS: The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect against the disease.The DQA1 label proved to be able to differentiate between 71.13 percent of the diabetic and non-diabetic individuals.This value increased to 82.47 percent when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups. CONCLUSIONS: The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles.
INTRODUÇÃO: O diabetes melito tipo 1 (T1ADM) é uma doença multifatorial em que os aspectos genéticos e ambientais são importantes para o seu desenvolvimento. A associação das variações genéticas com a doença tem sido demonstrada em vários trabalhos, no entanto, o papel de alguns locos gênicos não foi ainda completamente elucidado. OBJETIVOS: Comparar a frequência de alelos do HLA e polimorfismos nos genes CTLA-4 e insulina em brasileiros com T1ADM e indivíduos sem a doença, além de identificar marcadores gênicos que sejam capazes de discriminar indivíduos diabéticos e não diabéticos. MÉTODOS: A presença dos alelos de HLA DQB1, DQA1 e DRB1, bem como dos polimorfismos -2221 MspI no gene da insulina e 49 A/G no gene CTLA-4, foram identificados por meio da técnica Time-resolved fluorometer, após hibridização com sondas marcadas com Eu (III)/Sm (III) e Tb (III). RESULTADOS: Os alelos DQB1*0302 e DQA1*03 foram identificados como sendo de predisposição ao T1ADM, e o alelo DQB1*0301 mostrou um efeito protetor à doença. Analisando somente o marcador DQA1, este mostrou ser capaz de diferenciar 71,13 por cento dos indivíduos entre diabéticos e não diabéticos, cujo valor aumentou para 82,47 por cento quando adicionado o marcador DQB1. A frequência dos polimorfismos nos genes da insulina e CTLA-4 não mostrou diferença significativa entre os dois grupos estudados. CONCLUSÕES: Os marcadores genéticos que melhor caracterizaram e discriminaram diabéticos e não diabéticos foram os alelos de HLA DQA1 e DQB1.
Assuntos
Adolescente , Adulto , Humanos , Antígenos CD/genética , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-D/genética , Insulina/genética , Polimorfismo Genético/genética , Alelos , Estudos de Casos e Controles , Análise Discriminante , Frequência do Gene , Genótipo , Predisposição Genética para Doença/genéticaRESUMO
Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by a near total congenital absence of fat and predisposition to develop diabetes mellitus. In this study, we investigated the presence of mutations in the Seipin and 1-acylglycerol phosphate acyltransferase 2 (AGPAT2) genes in 32 affected subjects with BSCL from 17 consanguineous pedigrees living in two separate geographical regions, the northeastern and southeastern regions, of Brazil. All, except one, of the 22 BSCL subjects from 15 families living in the northeastern region were found to have a homozygous 669insA mutation in the Seipin gene. In contrast, all 10 BSCL subjects from two families living in the southeastern region were found to a have a homozygous 1036-bp deletion including exons 3 and 4 of AGPAT2. These results support genetic heterogeneity among BSCL patients in Brazil. Our finding of a single mutation in the Seipin and AGPAT2 genes in the pedigrees from the northeastern and southeastern regions, respectively, will be useful in genetic counseling of subjects from these large pedigrees from Brazil.
