Página 1 dos resultados de 611 itens digitais encontrados em 0.014 segundos

Validação cruzada com correção de autovalores e regressão isotônica nos modelos de efeitos principais aditivos e interação multiplicativa; Cross-validation with eigenvalue correction and isotonic regression in the additive main effect and multiplicative interaction model

PIOVESAN, Pamela; ARAÚJO, Lucio Borges de; DIAS, Carlos Tadeu dos Santos
Fonte: Universidade Federal de Santa Maria Publicador: Universidade Federal de Santa Maria
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
35.94%
Neste trabalho é apresentada a aplicação dos modelos AMMI com o propósito de analisar a interação entre genótipo e ambiente em experimentos agronômicos multiambientais com dados balanceados. São apresentados dois métodos de validação cruzada e o aperfeiçoamento desses métodos por meio da correção de autovalores, sendo estes ordenados por meio da regressão isotônica. É realizado um estudo comparativo entre esses métodos por meio de dados reais. Os resultados mostram para esse conjunto de dados que o método de EASTMENT & KRZANOWSKI (1982) seleciona um modelo mais parcimonioso. Além disso, quando esse método é aperfeiçoado com a correção dos autovalores, o número de componentes não se altera. O método de GABRIEL (2002) seleciona um maior número de termos no modelo, e, quando se aplica a correção de autovalores, o número de termos diminui. O aperfeiçoamento desses métodos por meio da correção de autovalores traz um grande benefício para o pesquisador do ponto de vista prático, uma vez que a seleção do número de termos multiplicativos representa um ganho do número de blocos (ou repetições), quando se utiliza o modelo AMMI em vez do modelo completo, sendo, portanto, melhor utilizar o modelo AMMI com correção dos autovalores e selecionar o número de componentes por meio do método de Eastment e Krzanowski.; This paper presents an application of AMMI models - Additive Main effects and Multiplicative Interaction model - for a thorough study about the effect of the interaction between genotype and environment in multi-environments experiments with balanced data. Two methods of crossed validation are presented and the improvement of these methods through the correction of eigenvalues...

Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo; Genotipagem do vírus da hepatite B de pacientes crônicos com resistência ao tratamento com lamivudina na Cidade de Ribeirão Preto, Estado de São Paulo

HADDAD, Rodrigo; MARTINELLI, Ana de Lourdes Candolo; UYEMURA, Sérgio Akira; YOKOSAWA, Jonny
Fonte: Sociedade Brasileira de Medicina Tropical - SBMT Publicador: Sociedade Brasileira de Medicina Tropical - SBMT
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.08%
INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58%) patients were infected with genotype D, 20 (40%) with genotype A and one (2%) with genotype F. Mutations in the YMDD motif occurred in 20% of the patients with genotype A and 27.6% of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.; INTRODUÇÃO: Lamivudina é um análogo de nucleosídeo clinicamente utilizado para o tratamento da infecção crônica pela hepatite B. Entretanto...

Circulation of Different Lineages of Dengue Virus 2, Genotype American/Asian in Brazil: Dynamics and Molecular and Phylogenetic Characterization

Drumond, Betânia Paiva; Mondini, Adriano; Schmidt, Diane J.; de Bronzoni, Roberta Vieira Morais; Bosch, Irene; Nogueira, Maurício Lacerda
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36%
The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time...

Analise molecular dos genotipos do virus da hepatite B em pacientes do estado de São Paulo, sudeste do Brasil; Molecular analysis of the genotypes of hepatitis B virus (HBV) in patients in state of São Paulo, Southeast of Brazil

Priscilla Aparecida Tonetto
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 22/08/2006 Português
Relevância na Pesquisa
26%
O vírus da hepatite B (VHB) pode ser classificado em oito principais genótipos (A-H), e essa classificação tem uma distribuição geográfica determinada. Os genótipos do VHB podem influenciar na progressão de doença. O objetivo foi determinar os genótipos e os subtipos do VHB e correlacioná-los com as variáveis clínicas epidemiológicas, laboratoriais e histológicas. Foram determinados os genótipos de 139 amostras de soro de pacientes infectados pelo VHB, coletadas em Campinas, no estado de São Paulo, Brasil. O método para genotipagem utilizado foi o seqüenciamento parcial do gene S do VHB. Os primers utilizados foram desenhados a partir de seqüências do gene S, com genótipo determinado, depositadas no GenBank. Todas as seqüências obtidas foram comparadas com as seqüências depositadas no GenBank para determinação dos genótipos. O genótipo A (55%) do VHB foi o mais predominante na população, seguido pelos genótipos C (3%), D (38%) e F (4%). Entre os pacientes infectados pelos genótipos A e D, observou-se uma provável descendência africana de 18% (14/76) e 11% (6/53), respectivamente. Entre os quatro pacientes infectados pelo genótipo C, dois possuíam descendência asiática e dois eram caucasianos. Todos os pacientes infectados pelo genótipo F eram caucasianos sem ascendência indígena relatada. Aproximadamente 30% dos pacientes eram HBeAg positivo e 70% eram HBeAg negativo. A carga viral do DNA-VHB foi aproximadamente cinco vezes mais alta entre os HBeAg positivo quando comparada aos HBeAg negativo. Os genótipos A e D são os mais prevalentes entre os pacientes...

Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo

Haddad,Rodrigo; Martinelli,Ana de Lourdes Candolo; Uyemura,Sérgio Akira; Yokosawa,Jonny
Fonte: Sociedade Brasileira de Medicina Tropical - SBMT Publicador: Sociedade Brasileira de Medicina Tropical - SBMT
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2010 Português
Relevância na Pesquisa
26.08%
INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58%) patients were infected with genotype D, 20 (40%) with genotype A and one (2%) with genotype F. Mutations in the YMDD motif occurred in 20% of the patients with genotype A and 27.6% of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.

Factor analysis and SREG GGE biplot for the genotype × environment interaction stratification in maize

Fritsche-Neto,Roberto; Miranda,Glauco Vieira; DeLima,Rodrigo Oliveira; Souza,Heraldo Namorato de
Fonte: Universidade Federal de Santa Maria Publicador: Universidade Federal de Santa Maria
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/05/2010 Português
Relevância na Pesquisa
46.08%
The objective of this study was to evaluate the use of SREG GGE biplot methodology and factor analysis to stratify the genotype×environment interaction in maize. Forty-nine early maize hybrids were evaluated in nine environments. The experimental design used was a 7×7 square lattice with two replicates. Each plot consisted of two 5m long rows spaced 0.90m apart. Grain yield data were used to perform the analysis. The results indicated the existence of two mega-environments in the State of Minas Gerais, Brazil, for early maize hybrids. The stratification of the environment by factor analysis was more selective to join the similarity the according with cultivar performance. However, this approach did not identify specific genotype x environment interactions, which is possible through SREG GGE biplot analysis.

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C

Pavan,Maria Helena Postal; Pavin,Elizabeth João; Gonçales Jr,Fernando Lopes; Zantut-Wittmann,Denise Engelbrecht
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2011 Português
Relevância na Pesquisa
26.02%
OBJECTIVE: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS: At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002...

gerbil: Genotype resolution and block identification using likelihood

Kimmel, Gad; Shamir, Ron
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26%
The abundance of genotype data generated by individual and international efforts carries the promise of revolutionizing disease studies and the association of phenotypes with individual polymorphisms. A key challenge is providing an accurate resolution (phasing) of the genotypes into haplotypes. We present here results on a method for genotype phasing in the presence of recombination. Our analysis is based on a stochastic model for recombination-poor regions (”blocks”), in which haplotypes are generated from a small number of core haplotypes, allowing for mutations, rare recombinations, and errors. We formulate genotype resolution and block partitioning as a maximum-likelihood problem and solve it by an expectation-maximization algorithm. The algorithm was implemented in a software package called gerbil (genotype resolution and block identification using likelihood), which is efficient and simple to use. We tested gerbil on four large-scale sets of genotypes. It outperformed two state-of-the-art phasing algorithms. The phase algorithm was slightly more accurate than gerbil when allowed to run with default parameters, but required two orders of magnitude more time. When using comparable running times, gerbil was consistently more accurate. For data sets with hundreds of genotypes...

Effects of Conserved RNA Secondary Structures on Hepatitis Delta Virus Genotype I RNA Editing, Replication, and Virus Production

Jayan, Geetha C.; Casey, John L.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2005 Português
Relevância na Pesquisa
26.02%
RNA editing of the hepatitis delta virus (HDV) antigenome at the amber/W site by the host RNA adenosine deaminase ADAR1 is a critical step in the HDV replication cycle. Editing is required for production of the viral protein hepatitis delta antigen long form (HDAg-L), which is necessary for viral particle production but can inhibit HDV RNA replication. The RNA secondary structural features in ADAR1 substrates are not completely defined, but base pairing in the 20-nucleotide (nt) region 3′ of editing sites is thought to be important. The 25-nt region 3′ of the HDV amber/W site in HDV genotype I RNA consists of a conserved secondary structure that is mostly base paired but also has asymmetric internal loops and single-base bulges. To understand the effect of this 3′ region on the HDV replication cycle, mutations that either increase or decrease base pairing in this region were created and the effects of these changes on amber/W site editing, RNA replication, and virus production were studied. Increased base pairing, particularly in the region 15 to 25 nt 3′ of the editing site, significantly increased editing; disruption of base pairing in this region had little effect. Increased editing resulted in a dramatic inhibition of HDV RNA synthesis...

Methicillin-Resistant Staphylococcus aureus (MRSA) Detection: Comparison of Two Molecular Methods (IDI-MRSA PCR Assay and GenoType MRSA Direct PCR Assay) with Three Selective MRSA Agars (MRSA ID, MRSASelect, and CHROMagar MRSA) for Use with Infection-Control Swabs▿

van Hal, S. J.; Stark, D.; Lockwood, B.; Marriott, D.; Harkness, J.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26%
Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing problem. Rapid detection of MRSA-colonized patients has the potential to limit spread of the organism. We evaluated the sensitivities and specificities of MRSA detection by two molecular methods (IDI-MRSA PCR assay and GenoType MRSA Direct PCR assay) and three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA), using 205 (101 nasal, 52 groin, and 52 axillary samples) samples from consecutive known MRSA-infected and/or -colonized patients. All detection methods had higher MRSA detection rates for nasal swabs than for axillary and groin swabs. Detection of MRSA by IDI-MRSA was the most sensitive method, independent of the site (94% for nasal samples, 80% for nonnasal samples, and 90% overall). The sensitivities of the GenoType MRSA Direct assay and the MRSA ID, MRSASelect, and CHROMagar MRSA agars with nasal swabs were 70%, 72%, 68%, and 75%, respectively. All detection methods had high specificities (95 to 99%), independent of the swab site. Extended incubation for a further 24 h with selective MRSA agars increased the detection of MRSA, with a corresponding decline in specificity secondary to a significant increase in false-positive results. There was a noticeable difference in test performance of the GenoType MRSA Direct assay in detection of MRSA (28/38 samples [74%]) compared with detection of nonmultiresistant MRSA (17/31 samples [55%]) (susceptible to two or more non-β-lactam antibiotics). This was not observed with selective MRSA agar plates or IDI-MRSA. Although it is more expensive...

FTO genotype is associated with exercise training-induced changes in body composition

Rankinen, Tuomo; Rice, Treva; Teran-Garcia, Margarita; Rao, D.C.; Bouchard, Claude
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.13%
The fat mass and obesity associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known if regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test if the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO SNP rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (p=0.004) but not in women (p=0.331; gene-by-sex interaction p=0.0053). The FTO genotype was associated with body fat responses to regular exercise (p<0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C-allele showed three times greater fat mass and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.

Delayed conduction and its implications in murine Scn5a+/− hearts: independent and interacting effects of genotype, age, and sex

Jeevaratnam, Kamalan; Poh Tee, Sui; Zhang, Yanmin; Rewbury, Rebecca; Guzadhur, Laila; Duehmke, Rudolf; Grace, Andrew A.; Lei, Ming; Huang, Christopher L.-H.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.02%
We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a+/− and wild type (WT) hearts. The investigated conditions of genotype, age, and sex affected latencies but not repolarization time courses of RV monophasic action potentials. This prompted examination of the patterns of RV epicardial activation, its dispersion, and their interrelationships as possible arrhythmic mechanisms using a 64-channel, multi-electrode array. Mean ventricular activation times (T*MEAN), spatial dispersions (D*S) between recording channels/cardiac cycle, and maximum activation times (T*MAX) representing the slowest possible conduction in any given heart were all higher in old male Scn5a+/− compared with young male and old female Scn5a+/− and old male WT. Temporal dispersions (D*T) of recording channels were similarly higher in old male Scn5a+/− compared with old male WT. All groupings of D*T, D*S, and T*MAX nevertheless linearly correlated with T*MEAN, with indistinguishable slopes. The variates explored thus influence D*T, D*S, and T*MAX through actions on T*MEAN. These findings in turn correlated with increased levels of fibrosis in young male...

Examining Overweight and Obesity as Risk Factors for Common Mental Disorders Using Fat Mass and Obesity-Associated (FTO) Genotype-Instrumented Analysis: The Whitehall II Study, 1985–2004

Kivimäki, Mika; Jokela, Markus; Hamer, Mark; Geddes, John; Ebmeier, Klaus; Kumari, Meena; Singh-Manoux, Archana; Hingorani, Aroon; Batty, G. David
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.02%
The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)2). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study (London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985–2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men—a finding that should be interpreted cautiously because the function of the FTO gene is unknown.

Testing different types of genotype-environment correlation: an extended children-of-twins model

Narusyte, Jurgita; Neiderhiser, Jenae M.; D’Onofrio, Brian M.; Reiss, David; Spotts, Erica L.; Ganiban, Jody; Lichtenstein, Paul
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/2008 Português
Relevância na Pesquisa
26%
This study presents an extended children-of-twins model, allowing us to test the direction of the association between parenting and child adjustment. Three mechanisms can be examined: direct phenotypic influence of parenting on child behavior (controlling for both parental and child genotype), passive genotype-environment correlation and evocative genotype-environment correlation. This model has been tested using Monte-Carlo simulations. We generated datasets consisting of 1000 twin parent pairs together with their children, and 1000 twin children pairs together with their parents. These simulated datasets were then used to estimate the model and the procedure was repeated 1000 times. The simulation results showed that our model recovered the true values of parameters with high precision. The model was also applied to an observed dataset to analyze, as a first example, the association between maternal emotional overinvolvement and child internalizing problems. The results showed that this association was best explained by evocative genotype-environment correlation.

Displacement of the Predominant Dengue Virus from Type 2 to Type 1 with a Subsequent Genotype Shift from IV to I in Surabaya, Indonesia 2008–2010

Yamanaka, Atsushi; Mulyatno, Kris C.; Susilowati, Helen; Hendrianto, Eryk; Ginting, Amor P.; Sary, Dian D.; Rantam, Fedik A.; Soegijanto, Soegeng; Konishi, Eiji
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 07/11/2011 Português
Relevância na Pesquisa
26.02%
Indonesia has annually experienced approximately 100,000 reported cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) in recent years. However, epidemiological surveys of dengue viruses (DENVs) have been limited in this country. In Surabaya, the second largest city, a single report indicated that dengue virus type 2 (DENV2) was the predominant circulating virus in 2003–2005. We conducted three surveys in Surabaya during: (i) April 2007, (ii) June 2008 to April 2009, and (iii) September 2009 to December 2010. A total of 231 isolates were obtained from dengue patients and examined by PCR typing. We found that the predominant DENV shifted from type 2 to type 1 between October and November 2008. Another survey using wild-caught mosquitoes in April 2009 confirmed that dengue type 1 virus (DENV1) was the predominant type in Surabaya. Phylogenetic analyses of the nucleotide sequences of the complete envelope gene of DENV1 indicated that all 22 selected isolates in the second survey belonged to genotype IV and all 17 selected isolates in the third survey belonged to genotype I, indicating a genotype shift between April and September 2009. Furthermore, in December 2010, isolates were grouped into a new clade of DENV1 genotype I...

Genotype Probabilities at Intermediate Generations in the Construction of Recombinant Inbred Lines

Broman, Karl W.
Fonte: Genetics Society of America Publicador: Genetics Society of America
Tipo: Artigo de Revista Científica
Publicado em /02/2012 Português
Relevância na Pesquisa
26.02%
The mouse Collaborative Cross (CC) is a panel of eight-way recombinant inbred lines: eight diverse parental strains are intermated, followed by repeated sibling mating, many times in parallel, to create a new set of inbred lines whose genomes are random mosaics of the genomes of the original eight strains. Many generations are required to reach inbreeding, and so a number of investigators have sought to make use of phenotype and genotype data on mice from intermediate generations during the formation of the CC lines (so-called pre-CC mice). The development of a hidden Markov model for genotype reconstruction in such pre-CC mice, on the basis of incompletely informative genetic markers (such as single-nucleotide polymorphisms), formally requires the two-locus genotype probabilities at an arbitrary generation along the path to inbreeding. In this article, I describe my efforts to calculate such probabilities. While closed-form solutions for the two-locus genotype probabilities could not be derived, I provide a prescription for calculating such probabilities numerically. In addition, I present a number of useful quantities, including single-locus genotype probabilities, two-locus haplotype probabilities, and the fixation probability and map expansion at each generation along the course to inbreeding.

Genotype Imputation for African Americans using data from HapMap Phase II versus 1000 Genomes Projects

Sung, Yun Ju; Gu, C Charles; Tiwari, Hemant K; Arnett, Donna K; Broeckel, Ulrich; Rao, DC
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.02%
Genotype imputation provides imputation of untyped SNPs that are present on a reference panel such as those from the HapMap Project. It is popular for increasing statistical power and comparing results across studies using different platforms. Imputation for African American populations is challenging because their LD blocks are shorter and also because no ideal reference panel is available due to admixture. In this paper, we evaluated three imputation strategies for African Americans. The intersection strategy used a combined panel consisting of SNPs polymorphic in both CEU and YRI. The union strategy used a panel consisting of SNPs polymorphic in either CEU or YRI. The merge strategy merged results from two separate imputations, one using CEU and the other using YRI. Because recent investigators are increasingly using the data from the 1000 Genomes (1KG) Project for genotype imputation, we evaluated both 1KG-based imputations and HapMap-based imputations. We used 23,707 SNPs from chromosomes 21 and 22 on Affymetrix SNP Array 6.0 genotyped for 1,075 HyperGEN African Americans. We found that 1KG-based imputations provided a substantially larger number of variants than HapMap-based imputations, about three times as many common variants and eight times as many rare and low frequency variants. This higher yield is expected because the 1KG panel includes more SNPs. Accuracy rates using 1KG data were slightly lower than those using HapMap data before filtering...

Cost-Effectiveness of Genotype Testing for Primary Resistance in Brazil

Luz, Paula M.; Morris, Bethany L.; Grinsztejn, Beatriz; Freedberg, Kenneth A.; Veloso, Valdilea G.; Walensky, Rochelle P.; Losina, Elena; Nakamura, Yoriko M.; Girouard, Michael P.; Sax, Paul E.; Struchiner, Claudio J.; Paltiel, A. David
Fonte: JAIDS Journal of Acquired Immune Deficiency Syndromes Publicador: JAIDS Journal of Acquired Immune Deficiency Syndromes
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.11%
Objective: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. Design: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). Methods: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as “cost-effective” compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12...

Genotype-phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies

Bunge, S.; Clements, P.; Byers, S.; Kleijer, W.; Brooks, D.; Hopwood, J.
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
Relevância na Pesquisa
36%
Fibroblasts from 16 patients with known alpha-L-iduronidase gene mutations and different clinical phenotypes of mucopolysaccharidosis type I (MPS I) were investigated in order to establish genotype/phenotype correlations. Enzyme kinetic studies were performed using the specific alpha-L-iduronidase substrate iduronosyl anhydro[1-3H]mannitol-6-sulfate. Specific residual enzyme activities were estimated using the kinetic parameters and an immunoquantification assay which determines levels of alpha-L-iduronidase protein. Cells were cultured in the presence of [35S]sulfate and the in vivo degradation of accumulated labelled glycosaminoglycans measured after different chase times. Residual enzyme activity and different amounts of residual enzyme protein were present in extracts from 9 of 16 cell lines covering a wide spectrum of clinical severity. Catalytic capacity, calculated as the product of kcat/Km and ng iduronidase protein per mg cell protein, was shown in most cases to be directly related to the severity of clinical phenotype, with up to 7% of normal values for patients with the attenuated form of MPS I (Scheie) and less than 0.13% for severely affected patients (Hurler) In vitro turnover studies allowed further refinement of correlations between genotype and phenotype. Scheie disease compared to Hurler disease patients were shown to accumulate smaller amounts of glycosaminoglycans that were also turned over faster. A combination of turnover and residual enzyme data established a correlation between the genotype...

TATES: Efficient Multivariate Genotype-Phenotype Analysis for Genome-Wide Association Studies

van der Sluis, Sophie; Posthuma, Danielle; Dolan, Conor V.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.07%
To date, the genome-wide association study (GWAS) is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in loss of statistical power to detect causal variants. Multivariate genotype–phenotype methods do exist but attain maximal power only in special circumstances. Here, we present a new multivariate method that we refer to as TATES (Trait-based Association Test that uses Extended Simes procedure), inspired by the GATES procedure proposed by Li et al (2011). For each component of a multivariate trait, TATES combines p-values obtained in standard univariate GWAS to acquire one trait-based p-value, while correcting for correlations between components. Extensive simulations, probing a wide variety of genotype–phenotype models, show that TATES's false positive rate is correct, and that TATES's statistical power to detect causal variants explaining 0.5% of the variance can be 2.5–9 times higher than the power of univariate tests based on composite scores and 1.5–2 times higher than the power of the standard MANOVA. Unlike other multivariate methods...