Sistema histo-sangüíneo ABO, status Secretor e anticorpos anti-Toxoplasma gondii em gestação da região Noroeste do Estado de São Paulo: um estudo de associação

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Polimorfismo dos genes ABO, Lewis e Secretor correlacionados com o câncer de mama

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Association of ABO gene mutations resulting in a rare B subgroup

Background and Objectives B subgroups are rare and the genetic analysis reported to date has been limited.Materials and Methods Serological and molecular investigations were performed in blood from a B-subgroup donor.Results Red cells did not react with anti-B and anti-AB reagents. However, cells absorbed anti-B. Red cells presented positive reactions with anti-H, and saliva secreted H substance. The molecular study demonstrated a B allele with the substitutions 467C>T, 646T>A, 681G>A, 771C>T, 796C>A, 803G>C, 829G>A and an 0 allele with the sequence of 002.Conclusions It is probable that the presence in exon 7 of some of the 002 substitutions could have weakened the enzymatic activity of the encoded B transferase.

Expression cloning of Forssman glycolipid synthetase: a novel member of the histo-blood group ABO gene family.

A phenotypic cloning approach was used to isolate a canine cDNA encoding Forssman glycolipid synthetase (FS; UDP-GalNAc:globoside alpha-1,3-N-acetylgalactosaminyltransferase; EC 2.4.1.88). The deduced amino acid sequence of FS demonstrates extensive identity to three previously cloned glycosyltransferases, including the enzymes responsible for synthesis of histo-blood group A and B antigens. These three enzymes, like FS, catalyze the addition of either N-acetylgalactosamine (GalNAc) or galactose (Gal) in alpha-1,3-linkage to their respective substrates. Despite the high degree of sequence similarity among the transferases, we demonstrate that the FS cDNA encodes an enzyme capable of synthesizing Forssman glycolipid, and demonstrates no GalNAc or Gal transferase activity when closely related substrates are examined. Thus, the FS cDNA is a novel member of the histo-blood group ABO gene family that encodes glycosyltransferases with related but distinct substrate specificity. Cloning of the FS cDNA will allow a detailed dissection of the roles Forssman glycolipid plays in cellular differentiation, development, and malignant transformation.

ABO genotyping in leukemia patients reveals new ABO variant alleles

The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic myeloid leukemia (N = 69), chronic lymphoid leukemia (N = 13), acute myeloid leukemia (N = 15), and acute lymphoid leukemia (N = 11). ABO genotyping was carried out using allele specific primer polymerase chain reaction followed by DNA sequencing. ABO*001 was the most common allele found, followed by ABO*022 and by ABO*A103. We identified 22 new ABO*(variants) in the coding region of the ABO gene in 25 individuals with leukemia (23.2%). The majority of ABO variants was detected in O alleles (15/60.0%). In 5 of 51 samples typed as blood group O (9.8%), we found non-deletional ABO*O alleles. Elucidation of the diversity of this gene in leukemia and in other diseases is important for the determination of the effect of changes in an amino acid residue on the specificity and activity of ABO glycosyltransferases and their function. In conclusion, this is the first report of a large number of patients with leukemia genotyped for ABO. The findings of this study indicate that there is a high level of recombinant activity in the ABO gene in leukemia patients, revealing new ABO variants.

Genetic characterization of the ABO blood group in Neandertals

Background: The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. Results: We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. Conclusion: These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence.

Amplification of the DFR1 gene in Saccaromyces cerevisiae

A new system was employed to study amplification of t,he DHF'R gene DFB,1 ) in Sa<,:;charoillYCB§. .Q~~Yi...S!i<;1~. . This system consists of a series of yeast strains containing a casset,te which encodes t he yeast, D..ERl gene ttghtly linked tjO a f usion of the yeast 1EU2. regulat,ory region wi tJ1 the LAQZ str ctural gene from E. cO.1-1 (,) . M. Clement , unpubl i,::;hed) . Th's casset;t e was shown t.o be integrat,ed int o a unj que chromosomal l ocati on in each strain . Yeast cells were se l ected for MTX-resistance and overproduction of ~ galac t osi d se ( B-gal ). Since the inserted DF'Rl and ~ACZ genes are independently regulated, it was thought that cel l s with this phenotype probably contain e d ampl if ications of the cassette. A lar ge variat ion in the f requn y o f MTX-resistance was found between the di ff e r ent str ains. These freqlen c ~ es r anged from about 2 x 10 - 7 fo r a population of cells containing the cassette integrated at, the BI J2.l gene in t,he middle of the long arm of chromosome V, to about 5 x 10-4 for a strain with the cassette i nserted in the r DNA cluster Abo It 85% of the MTX- res i stcmt iso l ates examined showed enhanced B·-gal act i v ity rel a t ive t o the parental strain . For the ma jorit y of strains, the mean B- gal activity in drug-r sistant clones was about 3 times that o f the parent following a single se l ect i on step . I n con t r ast, primary MTX-resistant derivat~ves of cells with the cassette inserted 3 at the rDNA cluster showed inc r eases in B- gal activity ranging from 9 - 14 f old r elative to the parent. Analysis of the latte r s train by Southe rn hybr idization indicated that the cassette was inde e d amplified several fold in MTX-re sistant derivatives. A sing l e strain, in which the cassette was inserted at the !lEA;], loc u.s , was used to examine in more detai 1 , the parameters affecting DFRl gene amplificat~ion in yeast . The mean B- gal activity in drug-resistant derivatives of this strain could be increased from 3 to 6 or 7 fold relative to the parent, by stepwise sel ection using increasing MTX concentrations. B-gal overproduction was found to be un stable in all primary and highly -resistant isolates examined. There was no indication, h owever, of a decrease i n growth r a t e in MTX-res i s tant cells which overproduced B - gal.

Lack of association between ABO histo-blood groups, secretor and non-secretor phenotypes, and anti-Toxoplasma gondii antibodies among pregnant women from the northwestern region of São Paulo State, Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

ABO blood groups and Helicobacter pylori cagA infection: evidence of an association

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genetic of the ABO blood system and its link with the immune system

Peter J. D'Adamo, autor do livro Eat Right For Your Type, escreve que o grupo O representa o primeiro tipo sangüíneo que surgiu nos humanos e também afirma que os grupos sangüíneos constituem as bases do sistema imune. Recentes estudos filogenéticos realizados em primatas humanos e não humanos estabeleceram que o gene A representa a forma ancestral dos genes que ocupam o locus ABO. Associações entre os grupos sangüíneos ABO, doenças infecciosas, não infecciosas e imunodeficiências também foram relatadas. Diante das proposições do autor, as quais se opõem às informações resultantes de recentes estudos moleculares e filogenéticos, nossa intenção é apresentar algumas reflexões sobre a genética e a evolução dos genes do sistema ABO e as conexões deste sistema com o sistema imune.

High intestinal cholesterol absorption is associated with cardiovascular disease and risk alleles in ABCG8 and ABO: evidence from the LURIC and YFS cohorts and from a meta-analysis.

OBJECTIVES This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). BACKGROUND Plant sterol-enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. METHODS The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorption because it is independent of plant sterols. First, we investigated the associations of 6 single nucleotide polymorphisms in ABCG8 and ABO with CR in the LURIC (LUdwisghafen RIsk and Cardiovascular health study) and the YFS (Young Finns Study) cohorts. Second, we conducted a systematic review and meta-analysis to investigate whether CR might be related to CVD. RESULTS In LURIC, the minor alleles of rs4245791 and rs4299376 and the major alleles of rs41360247, rs6576629, and rs4953023 of the ABCG8 gene and the minor allele of rs657152 of the ABO gene were significantly associated with higher CR. Consistent results were obtained for rs4245791, rs4299376, rs6576629, and rs4953023 in YFS. The meta-analysis, including 6 studies and 4,362 individuals, found that CR was significantly increased in individuals with CVD. CONCLUSIONS High cholesterol absorption is associated with risk alleles in ABCG8 and ABO and with CVD. Harm caused by elevated cholesterol absorption rather than by plant sterols may therefore mediate the relationships of ABCG8 and ABO variants with CVD.

Graphene And Carbon Nanotube Nanocomposite For Gene Transfection.

Graphene and carbon nanotube nanocomposite (GCN) was synthesised and applied in gene transfection of pIRES plasmid conjugated with green fluorescent protein (GFP) in NIH-3T3 and NG97 cell lines. The tips of the multi-walled carbon nanotubes (MWCNTs) were exfoliated by oxygen plasma etching, which is also known to attach oxygen content groups on the MWCNT surfaces, changing their hydrophobicity. The nanocomposite was characterised by high resolution scanning electron microscopy; energy-dispersive X-ray, Fourier transform infrared and Raman spectroscopies, as well as zeta potential and particle size analyses using dynamic light scattering. BET adsorption isotherms showed the GCN to have an effective surface area of 38.5m(2)/g. The GCN and pIRES plasmid conjugated with the GFP gene, forming π-stacking when dispersed in water by magnetic stirring, resulting in a helical wrap. The measured zeta potential confirmed that the plasmid was connected to the nanocomposite. The NIH-3T3 and NG97 cell lines could phagocytize this wrap. The gene transfection was characterised by fluorescent protein produced in the cells and pictured by fluorescent microscopy. Before application, we studied GCN cell viability in NIH-3T3 and NG97 line cells using both MTT and Neutral Red uptake assays. Our results suggest that GCN has moderate stability behaviour as colloid solution and has great potential as a gene carrier agent in non-viral based therapy, with low cytotoxicity and good transfection efficiency.

Carbon Nanoparticles For Gene Transfection In Eukaryotic Cell Lines.

For the first time, oxygen terminated cellulose carbon nanoparticles (CCN) was synthesised and applied in gene transfection of pIRES plasmid. The CCN was prepared from catalytic of polyaniline by chemical vapour deposition techniques. This plasmid contains one gene that encodes the green fluorescent protein (GFP) in eukaryotic cells, making them fluorescent. This new nanomaterial and pIRES plasmid formed π-stacking when dispersed in water by magnetic stirring. The frequencies shift in zeta potential confirmed the plasmid strongly connects to the nanomaterial. In vitro tests found that this conjugation was phagocytised by NG97, NIH-3T3 and A549 cell lines making them fluorescent, which was visualised by fluorescent microscopy. Before the transfection test, we studied CCN in cell viability. Both MTT and Neutral Red uptake tests were carried out using NG97, NIH-3T3 and A549 cell lines. Further, we use metabolomics to verify if small amounts of nanomaterial would be enough to cause some cellular damage in NG97 cells. We showed two mechanisms of action by CCN-DNA complex, producing an exogenous protein by the transfected cell and metabolomic changes that contributed by better understanding of glioblastoma, being the major finding of this work. Our results suggested that this nanomaterial has great potential as a gene carrier agent in non-viral based therapy, with low cytotoxicity, good transfection efficiency, and low cell damage in small amounts of nanomaterials in metabolomic tests.

Identification Of Target Genes Using Gene Expression Profile Of Granulocytes From Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.

Iis--integrated Interactome System: A Web-based Platform For The Annotation, Analysis And Visualization Of Protein-metabolite-gene-drug Interactions By Integrating A Variety Of Data Sources And Tools.

High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted. We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web. We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two-hybrid, proteomics and metabolomics datasets, but it is also extendable to other datasets. IIS is freely available online at: http://www.lge.ibi.unicamp.br/lnbio/IIS/.