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Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

LYRA, P.P.R.; DINIZ, E.M.A.; ABE-SANDES, K.; ANGELO, A.L.D.; MACHADO, T.M.B.; CARDEAL, M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.06%
The etiology of respiratory distress syndrome (RDS) is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B) gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53%) girls and 37 (47%) boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA) was 33.9 weeks (range: 29 to 35 weeks and 6 days). The RDS group consisted of 31 (43%) girls and 41 (57%) boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks). The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629). We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis

Parra, Eliane Soler; Panzoldo, Natalia Baratella; Kaplan, Denise; Oliveira, Helena Coutinho Franco de; Santos, Jose Ernesto dos; Fernandes de Carvalho, Luiz Sergio; Spósito, Andrei Carvalho; Gidlund, Magnus Ake; Nakamura, Ruy Tsutomu; Souza Zago, Vanessa
Fonte: BIOMED CENTRAL LTD; LONDON Publicador: BIOMED CENTRAL LTD; LONDON
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.12%
Background: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. Methods: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-a concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. Results: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT...

Mannose-binding lectin and MBL-associated serine protease-2 gene polymorphisms in a Brazilian population from Rio de Janeiro

Ferraroni, N. R.; Segat, L.; Guimaraes, R. L.; Brandao, L. A. C.; Crovella, S.; Constantino-Silva, R. N.; Loja, C.; da Silva Duarte, A. J.; Grumach, A. S.
Fonte: WILEY-BLACKWELL; MALDEN Publicador: WILEY-BLACKWELL; MALDEN
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.06%
Mannose-binding lectin (MBL) is a protein able to bind to carbohydrate patterns on pathogen membranes; upon MBL binding, its associated serine protease MBL-associated serine protease type 2 (MASP2) is autoactivated, promoting the activation of complement via the lectin pathway. For both MBL2 and MASP2 genes, the frequencies of polymorphisms are extremely variable between different ethnicities, and this aspect has to be carefully considered when performing genetic studies. While polymorphisms in the MBL-encoding gene (MBL2) have been associated, depending upon ethnicity, with several diseases in different populations, little is known about the distribution of MASP2 gene polymorphisms in human populations. The aim of our study was thus to determine the frequencies of MBL2 (exon 1 and promoter) and MASP2 (p.D371Y) polymorphisms in a Brazilian population from Rio de Janeiro. A total of 294 blood donor samples were genotyped for 27 polymorphisms in the MBL2 gene by direct sequencing of a region spanning from the promoter polymorphism H/L rs11003125 to the rs1800451 polymorphism (at codon 57 in the first exon of the gene). Genotyping for MASP2 p.D371Y was carried out using fluorogenic probes. To our knowledge, this is the first study reporting the prevalence of the MASP2 p.D371Y polymorphism in a Brazilian population. The C allele frequency 39% is something intermediate between the reported 14% in Europeans and 90% in Sub-Saharan Africans. MBL2 polymorphisms frequencies were quite comparable to those previously reported for admixed Brazilians. Both MBL2 and MASP2 polymorphisms frequencies reported in our study for the admixed Brazilian population are somehow intermediate between those reported in Europeans and Africans...

Análise de polimorfismos do gene que codifica a proteína B do surfactante: comparação entre recém-nascidos pré-termo com e sem síndrome do desconforto respiratório; Surfactant protein B gene polymorphisms analysis: comparison between preterm newborns with and without respiratory distress syndrome

Lyra, Priscila Pinheiro Ribeiro
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 01/07/2010 PT
Relevância na Pesquisa
36.11%
A síndrome do desconforto respiratório (SDR) é causada pela deficiência transitória de surfactante pulmonar em recém-nascidos (RN) prematuros nos primeiros dias de vida. Estudos sugerem que a etiologia da SDR seja multifatorial e multigênica. A proteína B do surfactante (SP-B) é fundamental para o metabolismo do surfactante e para uma função pulmonar normal. A presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da SP-B, parece estar associada à SDR. Objetivos: Determinar a freqüência de polimorfismos do gene que codifica a proteína B do surfactante no DNA de recém nascidos pré-termo com e sem SDR, comparar as freqüências desses polimorfismos entre os dois grupos e avaliar se existe alguma relação entre sexo, raça e SDR. Casuística e Métodos: Foram incluídos no estudo 151 RNPT, sendo 79 sem SDR com idades gestacionais variando entre 29 semanas e 35 semanas e 6 dias e 72 RN pré-termo com SDR com idades gestacionais variando de 26 a 35 semanas. Foram analisados quatro polimorfismos: A/C no nucleotídeo - 18; C/T no nucleotídeo 1580; A/G no nucleotídeo 9306 e G/C no nucleotídeo 8714. Os polimorfismos foram determinados através da amplificação dos segmentos de DNA genômico por reação em cadeia da polimerase e posterior genotipagem. Os genótipos foram definidos através da análise dos produtos obtidos a partir de reações com enzimas de restrição [PCR-based converted restriction fragment length polymorphism (cRFLP)]. Resultados: O grupo Controle foi constituído por 79 RN pré-termo sem SDR; sendo 42 (53...

Análise de polimorfismos do gene que codifica a proteína B do surfactante: comparação entre recém-nascidos de termo sadios e recém-nascidos pré-termo com síndrome do desconforto respiratório; Surfactant protein B gene polymorphisms analysis: comparison between healthy term and preterm newborns with respiratory distress syndrome

Lyra, Priscila Pinheiro Ribeiro
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 10/01/2005 PT
Relevância na Pesquisa
36.06%
A etiologia da síndrome do desconforto respiratório (SDR) é considerada multifatorial e multigênica. A proteína B do surfactante (SP-B) é essencial para a função pulmonar normal. O gene responsável pela produção da SP-B está localizado no braço curto do cromossomo 2 (2p12->p11.2), estendendo-se por aproximadamente por 9.5 Kilobases e contém 11 exons. A presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da SP-B, parece estar associada à SDR. Objetivos: Determinar a freqüência de polimorfismos do gene que codifica a proteína B do surfactante no DNA de recém nascidos pré-termo portadores de SDR e de recémnascidos de termo sadios, comparar as freqüências desses polimorfismos entre os dois grupos e avaliar se existe alguma relação entre sexo, raça e SDR. Casuística e Métodos: Foram incluídos no estudo 150 RN, sendo 50 pré-termo portadores de SDR com idades gestacionais variando entre 28 e 33 semanas e 6 dias, e 100 RN de termo clinicamente sadios com idades gestacionais variando de 37 a 41 semanas e seis dias, no período de junho de 2001 a julho de 2004. Foram analisados quatro polimorfismos: A/C no nucleotídeo - 18; C/T no nucleotídeo 1580; A/G no nucleotídeo 9306 e G/C no nucleotídeo 8714. Os polimorfismos foram determinados através da amplificação dos segmentos de DNA genômico por reação em cadeia da polimerase e posterior genotipagem. Os genótipos foram definidos através da análise dos produtos obtidos a partir de reações com enzimas de S . 22 restrição [PCR-based converted restriction fragment length polymorphism (cRFLP)]. Resultados: O grupo controle foi constituído por 100 RN de termo aparentemente saudáveis; 42(42%) do sexo feminino e 58(58%) do sexo masculino; 39(39%) da raça branca e 61(61%) da raça não branca. O peso variou de 2280g a 4.740g (média de 3.239...

Single nucleotide polymorphisms at 15 codons of the prison protein gene from a scrapie-affected herd of Suffolk sheep in Brazil; Polimor ismos de nucleotídeos únicos em 15 códons do gene da proteína priônica em um rebanho Suffolk afetado com scrapie no Brasil

Andrade, Caroline Pinto de; Castro, Luiza Amaral de; Silva, Sergio Ceroni da; Almeida, Laura Lopes de; Driemeier, David
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
Relevância na Pesquisa
36.05%
Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc). This isoform presents an altered conformation that leads to aggregation in the host’s central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be in luenced by speci ic genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal’s genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171). The most variable codon was 171, where all described alleles were identi ied. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons...

The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis

Parra, Eliane Soler; Panzoldo, Natalia Baratella; Kaplan, Denise; Franco de Oliveira, Helena Coutinho; dos Santos, Jose Ernesto; Fernandes de Carvalho, Luiz Sergio; Sposito, Andrei Carvalho; Gidlund, Magnus; Nakamura, Ruy Tsutomu; de Souza Zago, Vanessa H
Fonte: Biomed Central Ltd; London Publicador: Biomed Central Ltd; London
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.11%
Background: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. Methods: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-a concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. Results: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT...

Milk protein polymorphisms in Brazilian Zebu cattle

Silva,Ivana Tramontina da; Del Lama,Marco Antonio
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/1997 EN
Relevância na Pesquisa
45.84%
Five bovine milk protein polymorphisms were studied in Zebuine cattle raised in Brazil, through horizontal electrophoresis on starch gel containing urea and 2-mercaptoethanol, using basic and acidic buffer systems. Allelic frequencies for a-La, b-Lg, aS1-Cn, b-Cn and k-Cn loci were estimated in six Gyr herds (N = 283), six Guzerat herds (N = 205), one Nelore herd (N = 17) and one Sindi herd (N = 22), all from São Paulo or Minas Gerais State, Brazil. Genotypic frequencies observed for each locus and breed studied are in accordance with the assumption of genetic equilibrium, demonstrating absence of high inbreeding levels for the breeds tested. The FST value found indicated significant genetic differentiation among breeds; however, the Gyr and Guzerat herds showed significantly different gene frequencies. Genetic distance estimates among zebuine breeds studied and the Holstein breed, taken as a reference for a taurine breed, showed strong differences between these two racial groups

Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

Lyra,P.P.R.; Diniz,E.M.A.; Abe-Sandes,K.; Angelo,A.L.D.; Machado,T.M.B.; Cardeal,M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2011 EN
Relevância na Pesquisa
36.06%
The etiology of respiratory distress syndrome (RDS) is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B) gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53%) girls and 37 (47%) boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA) was 33.9 weeks (range: 29 to 35 weeks and 6 days). The RDS group consisted of 31 (43%) girls and 41 (57%) boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks). The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629). We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

Genetic polymorphism and relationships among several swine populations of landrace, large white and duroc breeds

Tagliaro,Cláudia Helena; Franco,Maria Helena Lartigau Pereira; Weimer,Tania Azevedo
Fonte: Universidade Federal de Santa Maria Publicador: Universidade Federal de Santa Maria
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/1997 EN
Relevância na Pesquisa
45.84%
The data of three protein polymorphisms were used to investigate the genetic relationships among the Landrace, Large White and Duroc swine breeds reared in Brazil, 12 other populations of these same breeds from various countries and a population of Belgium Landrace. The dendrogram, constructed from matrix of genetic distance coefficients, disclosed three large groups clustered by breed. Among them, the Landrace and the Large White showed in average closer resemblance (D= 0.203) than between them and Duroc (D= 0.241). It the three breeds, the smallest genetic distances were found between Brazilian and Cuban pig populations (Landrace: D = 0.060; Large White: D = 0.052; Duroc: D = 0.065), although there were not reports of pig exchanges between these two countries.

Biochemical polymorphisms and genetic relationships between Brazilian and foreign breeds of pigs reared in Brazil

Tagliaro,Cláudia Helena; Franco,Maria Helena Lartigau Pereira; Schneider,Maria Paula Cruz; Brito,Benito Guimarães de; Barbosa,Antonio Stockler
Fonte: Universidade Federal de Santa Maria Publicador: Universidade Federal de Santa Maria
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/1999 EN
Relevância na Pesquisa
45.84%
The genetic variability of 14 protein systems encoded by 15 structural loci was investigated in blood samples of Piau and Caruncho pig breeds. The results were compared with those obtained previously for samples of Landrace, Large White, Duroc and Mouro. The degree of genetic variability obtained for Piau (He=0.114) was similar to that estimated for other breeds reared in Brazil (Landrace, He=0.116; Large White, He=0.119; Duroc, 0.095; Mouro, He= 0.130). Caruncho showed the lowest variability (He= 0.056). The gene frequencies at the polymorphic loci were used to evaluate the usefulness of these systems for paternity testing and the combined probabilities of paternity exclusion were estimated at 58% for the Piau and 36% for the Caruncho breed. Analysis of genetic distances revealed that the greatest similarity observed was between Piau and Landrace (D=0.042). Caruncho showed the greatest divergence among all breeds compared and the distances between this breed and others range from 0.107 (with Landrace) to 0.176 (with Duroc). The tree constructed by UPGMA and Rogers’ Distance gave a topology in which Piau and Mouro joined with the European breeds (Landrace and Large White) whereas Caruncho was separated from all the other breeds. The results of the analysis of the Caruncho samples should be interpreted with caution since the number of animals studied was small.

Studies of blood groups and protein polymorphisms in the Brazilian horse breeds Mangalarga Marchador and Mangalarga (Equus caballus)

Lippi,Andréia Samaha; Mortari,Norma
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2003 EN
Relevância na Pesquisa
55.92%
Allelic frequencies at 12 loci (five blood groups: C, D, K, P, and U; and seven protein polymorphisms: Al, A1B, Es, Gc, Hb, PGD, and Tf), are given for two Brazilian horse breeds: Mangalarga Marchador and Mangalarga. The high genetic identity value found (96.0%) is consistent with their common origin, although, at some point of the development of Mangalarga Marchador, Mangalarga separated from the original stock. The expected average heterozygosity was higher in Mangalarga Marchador. The populations presented genetic differentiation, as shown by the statistically significant value of F ST. The nonsignificant F IS values showed that there was no appreciable consanguineous mating in any of the two populations. Exclusion probability calculated for the 12 loci was 87.0% and 86.5% for Mangalarga Marchador and Mangalarga, respectively. No genetic equilibrium was observed in the A1B, Tf, and Es loci of Mangalarga Marchador. The frequencies of blood factors A, Q, and T were calculated.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

Angelo,Ana Luiza Dias; Cavalcante,Lourianne Nascimento; Abe-Sandes,Kiyoko; Machado,Taisa Bonfim; Lemaire,Denise Carneiro; Malta,Fernanda; Pinho,Joao Renato; Lyra,Luiz Guilherme Costa; Lyra,Andre Castro
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 EN
Relevância na Pesquisa
36.12%
OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein...

Statistical analyses of Drosophila and human protein polymorphisms.

Ota, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1975 EN
Relevância na Pesquisa
46.03%
By using the distribution function of allelic frequencies which was recently derived by Kimura and Ota for the model of stepwise production of neutral alleles, the observed protein polymorphisms of Drosophila and man are tested for fit to the theory of neutral protein variation. The observed and theoretical distributions of alleles agree quite well except for the excess of rare alleles in the actual distributions. In human polymorphisms, the alleles with frequencies less than 1% are more numerous than expected, whereas in Drosophila, those with frequencies less than 10% are more numerous. It is pointed out that these results support my thesis that mutational pressure rather than balancing selection is the main cause for the maintenance of protein polymorphisms.

Genetic Variation in Natural Populations of Five Drosophila Species and the Hypothesis of the Selective Neutrality of Protein Polymorphisms

Ayala, Francisco J.; Tracey, Martin L.; Barr, Lorraine G.; McDonald, John F.; Pérez-Salas, Santiago
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1974 EN
Relevância na Pesquisa
45.84%
We have studied genetic variation at 30–32 loci coding for enzymes in natural populations of five species of Drosophila. The average proportion of heterozygous loci per individual is 17.7 ± 0.4%. The average proportion of polymorphic loci per population is 69.2 ± 2.6% or 49.8 ± 2.2%, depending on what criterion of polymorphism is used. The following generalizations are advanced: (1) The amount of genetic polymorphism varies considerably from locus to locus. (2) At a given locus, populations of the same species are very similar in the amount and pattern of genetic variation. (3) However, at some loci large differences sometimes occur between local populations of the same species. (4) The amount of variation at a given locus is approximately the same in all five species. (5) When different species are compared, the pattern of the variation is either essentially identical or totally different at a majority of loci. We have tested the hypothesis that protein polymorphisms are selectively neutral by examining four predictions derived from the hypothesis. Our results are at variance with every one of the predictions. We have measured the amount of genetic differentiation, D, between taxa of various degrees of evolutionary divergence. The average value of D is 0.033 for local populations...

Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis

Acosta, Nicole; Quiroga, Andrés; Delgado, Pilar; Bravo, María Mercedes; Jaramillo, Carlos
Fonte: The WJG Press and Baishideng Publicador: The WJG Press and Baishideng
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.84%
AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies.

Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions

Serohijos, Adrian W.R.; Shakhnovich, Eugene I.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
36.1%
The patterns of polymorphisms in genomes are imprints of the evolutionary forces at play in nature. In particular, polymorphisms have been extensively used to infer the fitness effects of mutations and their dynamics of fixation. However, the role and contribution of molecular biophysics to these observations remain unclear. Here, we couple robust findings from protein biophysics, enzymatic flux theory, the selection against the cytotoxic effects of protein misfolding, and explicit population dynamics simulations in the polyclonal regime. First, we recapitulate results on the dynamics of clonal interference and on the shape of the DFE, thus providing them with a molecular and mechanistic foundation. Second, we predict that if evolution is indeed under the dynamic equilibrium of mutation–selection balance, the fraction of stabilizing and destabilizing mutations is almost equal among single-nucleotide polymorphisms segregating at high allele frequencies. This prediction is proven true for polymorphisms in the human coding region. Overall, our results show how selection for protein folding stability predominantly shapes the patterns of polymorphisms in coding regions.

Relationship of sclerostin and secreted frizzled protein polymorphisms with bone mineral density: an association study with replication in postmenopausal women

Valero Díaz de Lamadrid, Carmen; Zarrabeitia Cimiano, María Teresa; Hernández Hernández, José Luis; Pineda, Begoña; Cano, Antonio; García Pérez, Miguel A.; Riancho Moral, José Antonio
Fonte: Lippincott, Williams & Wilkins Publicador: Lippincott, Williams & Wilkins
Tipo: info:eu-repo/semantics/article; acceptedVersion
ENG
Relevância na Pesquisa
46.02%
Objectives.- Secreted frizzled-related protein and sclerostin, encoded by FRZB and SOST genes, respectively, are extracellular Wnt inhibitors that tend to decrease bone formation. The purpose of this study was to explore the association of sets of polymorphisms capturing common variations of these genes with bone mineral density (BMD). Methods.- Twelve polymorphic loci of the FRZB gene and 7 of the SOST gene were genotyped in postmenopausal women from two Spanish regions (Cantabria, n=1043, and Valencia, n=342). The polymorphisms included tagging SNPs and SNPs with possible functional consequences assessed in silico. Results.-The rs4666865 polymorphism of the FRZB gene was associated with spine BMD in the Cantabria cohort in the single-locus (p=0.008) and the haplotypic analysis. However, the results were not replicated in the Valencia cohort. Several polymorphisms at the 5´region of the SOST gene, and particularly rs851056, were associated with BMD in women from both cohorts (p=0.002 in Cantabria and 0.005 in Valencia). When the results of both cohorts were combined, the mean BMD difference across rs851056 genotypes was 47 mg/cm2 or 0.31 standard deviations (p<0.001). No differences in FRZB and SOST expression was detected across genotypes. Conclusions.- Polymorphisms in the 5’ region of SOST gene are associated with BMD in postmenopausal women...

Testing for Selective Neutrality of Electrophoretically Detectable Protein Polymorphisms

Weir, B. S.; Brown, A. H. D.; Marshall, D. R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1976 EN
Relevância na Pesquisa
45.92%
The statistical assessment of gene-frequency data on protein polymorphisms in natural populations remains a contentious issue. Here we formulate a test of whether polymorphisms detected by electrophoresis are in accordance with the stepwise, or charge-state, model of mutation in finite populations in the absence of selection. First, estimates of the model parameters are derived by minimizing chi-square deviations of the observed frequencies of genotypes with alleles (0,1,2...) units apart from their theoretical expected values. Then the remaining deviation is tested under the null hypothesis of neutrality. The procedure was found to be conservative for false rejections in simulation data. We applied the test to Ayala and Tracey 's data on 27 allozymic loci in six populations of Drosophila willistoni . About one-quarter of polymorphic loci showed significant departure from the neutral theory predictions in virtually all populations. A further quarter showed significant departure in some populations. The remaining data showed an acceptable fit to the charge state model. A predominating mode of selection was selection against alleles associated with extreme electrophoretic mobilities. The advantageous properties and the difficulties of the procedure are discussed.

Dysfunctional Crohn's disease-associated NOD2 polymorphisms cannot be reliably predicted on the basis of RIPK2-binding or membrane association

Parkhouse, Rhiannon; Monie, Tom P.
Fonte: Frontiers Publicador: Frontiers
Tipo: Article; published version
EN
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This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fimmu.2015.00521; Polymorphisms in NOD2 represent the single greatest genetic risk factor for the development of Crohn's disease. Three different non-synonomous NOD2 polymorphisms - R702W, G908R, L1007fsincC - account for roughly 80 % of all NOD2-associated cases of Crohn's disease and are reported to result in a loss of receptor function in response to muramyl dipeptide stimulation. Loss of NOD2 signalling can result from a failure to detect ligand; alterations in cellular localization; and changes in protein interactions, such as an inability to interact with downstream adaptor protein RIPK2. Using an overexpression system we analysed approximately 50 NOD2 polymorphisms reportedly connected to Crohn's disease to determine if they also displayed loss of function and if this could be related to alterations in protein localization and/or association with RIPK2. Just under half the polymorphisms displayed a significant reduction in signalling capacity following ligand stimulation, with nine of them showing near complete ablation. Only two polymorphisms, R38M and R138Q, lost the ability to interact with RIPK2. However, both these polymorphisms still associated with cellular membranes. In contrast...