Genotipagem de leveduras presentes no processo industrial de produção de álcool combustível e estudo do polimorfismo de genes envolvidos no processo fermentativo em Saccharomyces cerevisiae

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento de marcadores SNPs (Single Nucleotide Polymorphisms) para estudos populacionais do mosquito Aedes aegypti no Brasil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Valor prognóstico do SNP TP53 ARG72PRO na susceptibilidade ao desenvolvimento e na sobrevida de pacientes brasileiros com meduloblastoma

O Meduloblastoma é a neoplasia encefálica mais comum na infância, correspondendo a taxas de 16 a 25% de todos os tumores encefálicos em menores de 19 anos e 30-40% de todos os tumores da fossa posterior. Para investigar o papel do polimorfismo de base única (SNP) TP53 Arg72Pro sobre o risco de desenvolvimento, prognóstico e resposta a terapêutica adjuvante em Meduloblastoma, foi realizado um estudo caso-controle com 122 pacientes e 122 controles saudáveis do Brasil. Em comparação com Arg/Arg, que é o genótipo mais comum na população em estudo, tanto o genótipo Arg/Pro e Pro/Pro não influenciaram o risco de desenvolvimento de Meduloblastoma (OR = 1,36 e P = 0,339 para o genótipo Arg/Pro; OR = 1,50 e P = 0,389 para o genótipo Pro/Pro). Com relação ao prognóstico, a sobrevida livre de doença não foi significativamente diferente entre os genótipos SNP TP53 Arg72Pro (P> 0,05), porém o genótipo menos freqüente, Pro/Pro, foi associado a uma menor sobrevida global dos pacientes com Meduloblastoma (P = 0,021 ). Estes dados sugerem que embora não haja nenhuma associação entre o SNP TP53 Arg72Pro e o risco de desenvolvimento de Meduloblastoma, o genótipo Pro/Pro está associado a uma menor sobrevida global dos pacientes submetidos a terapia adjuvante. No entanto, devido à composição interétnica da população brasileira, futuros estudos envolvendo populações maiores e de outras partes do mundo serão essenciais para uma conclusão definitiva da função do SNP TP53 Arg72Pro.

Associação do perfil de acetilação lenta do gene NAT2 na susceptibilidade ao câncer, na Região Norte do Brasil

Objetivos: O gene N-acetiltransferase 2 (NAT2) é um marcador para o estudo da susceptibilidade interindividual ao desenvolvimento de neoplasias malignas, visto que a enzima NAT2 participa da metabolização de agentes carcinogênicos e os polimorfismos de base única (SNP) do seu gene produzem enzimas com diferentes atividades, levando a acetilação lenta ou rápida de xenobióticos. O objetivo do presente estudo foi verificar uma possível associação entre os SNPS do gene NAT2 e a susceptibilidade ao acometimento de Adenocarcinoma gástrico ou Carcinoma ductal invasivo da mama em pacientes da região norte do Brasil. Material e Métodos: Os cinco polimorfismos de grande importância para a determinação do perfil de metabolização da enzima NAT2 (C282T, T341 C, C481 T, A803G e G857A) foram investigados por sequenciamento direto de 986 pares de bases, amplificados em duas reações de PCR, no total de 133 pacientes com câncer (63 com Câncer Gástrico e 70 com Câncer de Mama) e 89 indivíduos Controles. Para evitar interpretações espúrias decorrentes do subestruturamento populacional, empregamos um painel de 48 marcadores informativos de ancestralidade (IAM). Resultados: Encontramos diferenças estatísticas para a contribuição parental Africana e Européia, quando comparadas entre os grupos com Câncer e Controles, uma contribuição maior do grupo Africano foi detectada no grupo de estudo com câncer e, no grupo controle, foi detectada uma maior contribuição do grupo Europeu (p<0,001). Os genótipos do polimorfismo C282T dominante (TT + CT) apresentaram associação significativa (p<0,001; OR 3,076; Cl 95% 1,664-5,687) para a susceptibilidade as diferentes formas de Câncer investigadas. Foi observada uma associação significante do perfil de acetilação lenta e rápida com a susceptibilidade ao desenvolvimento das neoplasias investigadas (p=0,010; OR 3,054; Cl 95% 1,303-7,159) e (p= 0,041; OR 0,527 Cl 95% 0,280-0,973) evidenciando que indivíduos com o perfil acetilador lento apresentaram um risco aumentado em até três vezes no desenvolvimento de neoplasias quando comparado com os indivíduos controles. Conclusão: O controle genômico da ancestralidade foi efetivamente importante para a presente investigação possibilitando controlar o efeito da ancestralidade na associação do gene NAT2 para susceptibilidade ao câncer. Neste trabalho foi possivel evidenciar a forte influência do perfil de acetilação lenta do gene NAT2 de xenobióticos na susceptibilidade ao Câncer Gástrico e de Mama.

Metodologias e estratégias de imputação de marcadores genéticos em bovinos da raça Cachim

Pós-graduação em Genética e Melhoramento Animal - FCAV

Assinaturas de seleção em bovinos da raça Canchim

Pós-graduação em Genética e Melhoramento Animal - FCAV

Single nucleotide polymorphisms in candidate genes associated with gastrointestinal nematode infection in goats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ocorrência do SNP c.767G>T no gene DNM1responsável pelo colapso induzido pelo exercício em cães da raça Labrador Retriever no Estado de São Paulo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A Key Management Protocol for Wireless Sensor Networks with Multiple Base Stations

Most of the proposed key management protocols for wireless sensor networks (WSNs) in the literature assume that a single base station is used and that the base station is trustworthy. However, there are applications in which multiple base stations are used and the security of the base stations must be considered. This paper investigates a key management protocol in wireless sensor networks which include multiple base stations. We consider the situations in which both the base stations and the sensor nodes can be compromised. The proposed key management protocol, mKeying, includes two schemes, a key distribution scheme, mKeyDist, supporting multiple base stations in the network, and a key revocation scheme, mKeyRev, used to efficiently remove the compromised nodes from the network. Our analyses show that the proposed protocol is efficient and secure against the compromise of the base stations and the sensor nodes.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients

Diabet. Med. 29, e55e61 (2012) Abstract Aims The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. Methods We cross-sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. Results Genotype frequencies in the whole population were consistent with the HardyWeinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 +/- 0.1 vs. 6.2 +/- 0.1 mmol/l, P = 0.020) and waist circumference (94.5 +/- 0.6 vs. 96.3 +/- 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. Conclusions These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.

Evaluation of MLH1 I219V Polymorphism in Unrelated South American Individuals Suspected of Having Lynch Syndrome

Background: Some single-nucleotide polymorphisms are associated with higher risk of colorectal cancer development and are suggested to explain part of the genetic contribution to Lynch syndrome. Aim: To evaluate the mutL homolog 1 (MLH1) I219V polymorphism in 124 unrelated South American individuals suspected of having Lynch syndrome, based on frequency, association with pathogenic MLH1 and mutS homolog 2 (MSH2) mutation and clinical features. Materials and Methods: DNA was obtained from peripheral blood and polymerase chain reaction (PCR) was performed, followed by direct sequencing. Results: The Val allelic of the I219V polymorphism was found in 51.61% (64/124) of the individuals, with an allelic frequency of 0.3. MLH1 or MHS2 pathogenic mutations were found in 32.81% (21/64) and in 23.33% (14/60) of Val-carriers and non-carriers, respectively. Conclusion: The Val-carrying genotype was frequent in the studied population; however, it does not appear to exert any modifier effect on MLH1 or MSH2 pathogenic mutations and the development of colorectal cancer.

Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5

SERA5 is regarded as a promising malaria vaccine candidate of the most virulent human malaria parasite Plasmodium falciparum. SERA5 is a 120 kDa abundantly expressed blood-stage protein containing a papain-like protease. Since substantial polymorphism in blood-stage vaccine candidates may potentially limit their efficacy, it is imperative to fully investigate polymorphism of the SERA5 gene (sera5). In this study, we performed evolutionary and population genetic analysis of sera5. The level of inter-species divergence (kS = 0.076) between P. falciparum and Plasmodium reichenowi, a closely related chimpanzee malaria parasite is comparable to that of housekeeping protein genes. A signature of purifying selection was detected in the proenzyme and enzyme domains. Analysis of 445 near full-length P. falciparum sera5 sequences from nine countries in Africa, Southeast Asia, Oceania and South America revealed extensive variations in the number of octamer repeat (OR) and serine repeat (SR) regions as well as substantial level of single nucleotide polymorphism (SNP) in non-repeat regions (2562 bp). Remarkably, a 14 amino acid sequence of SERA5 (amino acids 59-72) that is known to be the in vitro target of parasite growth inhibitory antibodies was found to be perfectly conserved in all 445 worldwide isolates of P. falciparum evaluated. Unlike other major vaccine target antigen genes such as merozoite surface protein-1, apical membrane antigen-1 or circumsporozoite protein, no strong evidence for positive selection was detected for SNPs in the non-repeat regions of sera5. A biased geographical distribution was observed in SNPs as well as in the haplotypes of the sera5 OR and SR regions. In Africa, OR- and SR-haplotypes with low frequency (<5%) and SNPs with minor allele frequency (<5%) were abundant and were mostly continent-specific. Consistently, significant genetic differentiation, assessed by the Wright's fixation index (FST) of inter-population variance in allele frequencies, was detected for SNPs and both OR- and SR-haplotypes among almost all parasite populations. The exception was parasite populations between Tanzania and Ghana, suggesting frequent gene flow in Africa. The present study points to the importance of investigating whether biased geographical distribution for SNPs and repeat variants in the OR and SR regions affect the reactivity of human serum antibodies to variants. (C) 2011 Elsevier Ltd. All rights reserved.

Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C > A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

Crohn's disease-associated polymorphism within the PTPN2 gene affects muramyl-dipeptide-induced cytokine secretion and autophagy

The single nucleotide polymorphism (SNP) rs2542151 within the gene locus region encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) has been associated with Crohn's disease (CD), ulcerative colitis (UC), type-I diabetes, and rheumatoid arthritis. We have previously shown that PTPN2 regulates mitogen-activated protein kinase (MAPK) signaling and cytokine secretion in human THP-1 monocytes and intestinal epithelial cells (IEC). Here, we studied whether intronic PTPN2 SNP rs1893217 regulates immune responses to the nucleotide-oligomerization domain 2 (NOD2) ligand, muramyl-dipeptide (MDP).

Assessment of D216H DYT1 polymorphism in a Chinese primary dystonia patient cohort

The D216H single-nucleotide polymorphism (SNP) (rs1801968) in DYT1 exon 4 has been suggested to be a genetic modifier in primary dystonia.