Determination of βS haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5%) were identified with genotype CAR/CAR, 9 (19.1%) CAR/BEN, 6 (12.8%) CAR/CAM, 1 (2.1%) BEN/BEN, 2 (4.3%) CAR/Atp, 1 (2.1%) BEN/Atp and 1 (2.1%) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte

The Priority position paper: protecting Europe's food chain from prions

International audienceBovine spongiform encephalopathy (BSE) created a global European crisis in the 1980s and 90s, with very serious health and economic implications. Classical BSE now appears to be under control, to a great extent as a result of a global research effort that identified the sources of prions in meat and bone meal (MBM) and developed new animal-testing tools that guided policy. Priority ( www.prionpriority.eu ) was a European Union (EU) Framework Program 7 (FP7)-funded project through which 21 European research institutions and small and medium enterprises (SMEs) joined efforts between 2009 and 2014, to conduct coordinated basic and applied research on prions and prion diseases. At the end of the project, the Priority consortium drafted a position paper ( www.prionpriority.eu/Priority position paper) with its main conclusions. In the present opinion paper, we summarize these conclusions. With respect to the issue of re-introducing ruminant protein into the feed-chain, our opinion is that sustaining an absolute ban on feeding ruminant protein to ruminants is essential. In particular, the spread and impact of non-classical forms of scrapie and BSE in ruminants is not fully understood and the risks cannot be estimated. Atypical prion agents will probably continue to represent the dominant form of prion diseases in the near future in Europe. Atypical L-type BSE has clear zoonotic potential, as demonstrated in experimental models. Similarly, there are now data indicating that the atypical scrapie agent can cross various species barriers. More epidemiological data from large cohorts are necessary to reach any conclusion on the impact of its transmissibility on public health. Re-evaluations of safety precautions may become necessary depending on the outcome of these studies. Intensified searching for molecular determinants of the species barrier is recommended, since this barrier is key for important policy areas and risk assessment. Understanding the structural basis for strains and the basis for adaptation of a strain to a new host will require continued fundamental research, also needed to understand mechanisms of prion transmission, replication and how they cause nervous system dysfunction and death. Early detection of prion infection, ideally at a preclinical stage, also remains crucial for development of effective treatment strategies

G6pd Sumaré: A Novel Mutation In The G6pd Gene (1292 T-->g) Associated With Chronic Nonspherocytic Anemia.

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Molecular Identification Of Sicilian (deltabeta) Degrees-thalassemia Associated With Beta-thalassemia And Hemoglobin S In Brazil.

We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (deltabeta) degrees -thalassemia with hemoglobin S and beta-thalassemia. Direct sequencing of the beta-globin gene showed only the hemoglobin S mutation in patient 1 and the beta-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 bp, expected to be observed in the DNA of carriers of Sicilian (deltabeta) degrees -thalassemia. The nucleotide sequence of this fragment confirmed the Sicilian deletion. There are few reports concerning the Hb S/(deltabeta) degrees -thalassemia association and patient 2 is the first reported case of Sicilian type of (deltabeta) degrees -thalassemia in association with beta-thalassemia documented at the molecular level.35873-

Effect Of α-thalassemia And β-globin Gene Cluster Haplotypes On The Hematological And Clinical Features Of Sickle-cell Anemia In Brazil

To compare the features of sickle-cell anemia in Brazil with those in other locales, we studied the effects of the β-globin-like gene cluster haplotype and α-thalassemia upon the clinical and hematological features in 85 patients, The distribution of haplotypes differed from that in the United States and Jamaica, The Central African Republic (CAR) haplotype predominated; 34% of patients were CAR haplotype homozygotes, 45% CAR/ Benin homozygotes, and 11% Benin homozygotes. No Senegal haplotype chromosomes were observed, α-thalassemia was present in 17.5% of patients, HbF levels were higher in Benin homozygotes, compared with the other two groups (P < 0.05). Nearly half the patients with a CAR haplotype had leg ulcers, compared to 12.5% of the Benin homozygote group; stroke did not occur in α-thalassemia carriers, but neither result was statistically Significant, As in other studies, our results indicate that the CAR haplotype may be associated with more severe disease.5327276Nagel, R.L., Rao, S.K., Dunda-Belkhodja, O., Connolly, M.M., Fabry, M.E., Georges, A., Krishnamoorthy, R., Labie, D., The hematologic characteristics of sickle cell anemia bearing the Bantu haplotype: The relationship between Gγ and HbF level (1987) Blood, 69, pp. 1026-1030Aluoch, J.R., Kilinç, Y., Aksoy, M., Yüregir, G.T., Bakioglu, I., Klutar, A., Kutlar, F., Huisman, T.H.J., Sickle cell anaemia among Eti-Turks: Haematological, clinical and genetic observations (1986) Br J Haematol, 64, pp. 45-55Schiliro, G., Samperi, P., Consalvo, C., Gangarossa, S., Teste, R., Miraglia, V., Lo Nigro, L., Clinical hematological, and molecular features in Sicilians with sickle cell disease (1992) Hemoglobin, 16, pp. 469-480Noguchi, C.T., Dover, G.H., Rodgers, G.P., Serjeant, G.R., Antonarakis, S.E., Anagnou, N.P., Higgs, D.R., Schechter, A.N., Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease (1985) J Clin Invest, 75, pp. 1632-1637Steinberg, M.H., Embury, S.H., α-thalassemia in blacks: Genetic and clinical aspects and interactions with the sickle hemoglobin gene (1986) Blood, 68, pp. 985-990Falusi, A.G., Kulozik, A.E., Relationship of foetal haemoglobin levels and βS haplotypes in homozygous sickle cell disease (1990) Eur J Haematol, 45, pp. 1-4Kulozik, A.E., Wainscoat, J.S., Serjeant, G.R., Kar, B.C., Al-Awamy, B., Essan, G.J.F., Falusi, A.G., Weatherall, D.J., Geographical survey of βS-globin gene haplotypes: Evidence for an independent Asian origin of the sickle-cell mutation (1986) Am J Hum Genet, 39, pp. 239-244Nagel, R.L., Erlingsson, S., Fabry, M.E., Croizat, H., Susuka, S.M., Lachman, H., Sutton, M., Billett, H.H., The Senegal DNA haplotype is associated with the amelioration of anemia in African-American sickle cell anemia patients (1991) Blood, 77, pp. 1371-1375Oner, C., Dimovski, A.J., Olivieri, N.F., Schiliro, G., Codrington, J.F., Fattoum, S., Adekile, A.D., Huisman, T.H.J., βS haplotypes in various world populations (1992) Hum Genet, 89, pp. 99-104Powars, D.R., Sickle cell anemia: βS-gene-cluster haplotypes as prognostic indicators of vital organ failure (1991) Semin Hematol, 28, pp. 202-208De Montalembert, M., Maier-Redelsperger, M., Girot, R., Belloy, M., Vilmer, E., Ducrocp, R., Guidal, C., Elion, J., β-globin gene cluster and α-thalassemia do not correlate with the acute clinical manifestations of sickle cell disease in children (1993) Blood, 82, pp. 2595-2596Rieder, R.F., Safaya, S., Gillette, P., Fryd, S., Hsu, H., Adams III, J.G., Steinberg, M.H., Effect of β-globin gene cluster haplotype on the hematological and clinical features of sickle cell anemia (1991) Am J Hematol, 36, pp. 184-189Gonçalves, M.S., Nechman, J.F., Figueiredo, M.S., Kerbauy, J., Arruda, V.R., Sonati, M.F., Saad, S.T.O., Stoming, T.A., Sickle cell anemia in a Brazilian population from São Paulo. A study of the βS haplotypes (1994) Hum Hered, 44, pp. 322-327Costa, F.F., Arruda, V.R., Gonçalves, M.S., Miranda, S.R.P., Carvalho, M.H., Sonati, M.F., Saad, S.T.O., Queiroz, I.L., BS-gene-cluster haplotypes in sickle cell anemia patients from two regions of Brazil (1994) Am J Hematol, 45, pp. 96-97Pembrey, M.E., McWade, P., Weatherall, D.J., Reliable routine estimation of small amounts of foetal haemoglobin by alkali denaturation (1972) J Clin Pathol, 25, pp. 738-740Poncz, M., Solwiejcyk, D., Harpel, B., Mory, Y., Schwartz, E., Surrey, S., Construction of human gene libraries from small amounts of peripheral human blood: Analysis of β-like globin genes (1982) Hemoglobin, 6, pp. 27-36Southern, E.M., Detection of specific sequences among DNA fragments separated by gel electrophoresis (1975) J Mol Biol, 98, pp. 503-517Sonati, M.F., Farah, S.B., Ramalho, A.S., Costa, F.F., High prevalence of deletional type of alpha thalassemia among a black population of Brazil (1991) Hemoglobin, 15, pp. 309-311Sutton, M., Bouhassira, E.E., Nagel, R.L., Polymerase chain reaction amplification applied to the determination of β-like globin gene cluster haplotypes (1989) Am J Hematol, 32, pp. 66-69Agresti, A., Finlay, B., (1986) Statistical Methods for the Social Sciences, , San Francisco: Dellen Publishing CoPagnier, J., Dunda-Belkhodja, O., Zohoun, I., Teyssier, J., Baya, H., Jaeger, G., Nagel, R.L., Labie, D., α-thalassemia among sickle cell anemia patients in various African populations (1984) Hum Genet, 68, pp. 318-319Castillo, R., Gay, R.N., Ballas, S.K., Homozygosity for the CAR β-haplotype in sickle in sickle cell anemia (SS) is associated with increased prevalence of α-gene deletion and leg ulcers (1992) Blood, 80, p. 199. , abstractHiggs, D.R., Aldridge, B.E., Lamb, J., Clegg, J.B., Weatherall, D.J., Hayes, R.J., Grandison, Y., Serjeant, G.R., The interaction of alpha-thalassemia and homozygous sickle-cell disease (1982) N Engl J Med, 306, pp. 1441-1446Schroeder, W.A., Powards, D.R., Kay, L.M., Chan, L.S., Huynh, V., Shelton, J.B., Shelton, J.R., β-cluster haplotypes, α-gene status, and hematological data from SS, SC, and S- β-thalasemia patients in Southern California (1989) Hemoglobin, 13, pp. 325-353Felice, A.E., Webber, B., Miller, A., Mayson, S.M., Harris, H.F., Henson, J.B., Gravely, M.E., Huisman, T.H.J., The association of sickle cell anemia with heterozygous and homozygous α-thalassemia-2: In vitro Hb chain synthesis (1979) Am J Hematol, 6, pp. 91-106Felice, A.E., McKie, K.M., Cleek, M.P., Marino, E.M., Kutlar, A., McKie, V.C., Effects of α-thalassemia-2 on the developmental changes of hematological values in children with sickle cell disease from Georgia (1987) Am J Hematol, 25, pp. 389-400McKie, V.C., McKie, K.M., Felice, A.E., α-thalassemia and cholelithiasis in children with SS disease (1987) Clin Res, 35, p. 64. , abstractBallas, S.K., Talacki, C.A., Rao, V.M., Steiner, R.M., The prevalence of avascular necrosis in sickle cell anemia: Correlation with α-thalassemia (1989) Hemoglobin, 13, pp. 649-655Piomelli, S., Seaman, C., Cirella, B., Ince, C., Meyer, P., Pavlakis, S., Schaefer-Rego, K., Mears, G., Does alpha-thalassemia protect from early stroke sickle-cell anemia? (1986) Pediatr Res, 20, p. 285. , abstractAdams, R.J., Kutlar, A., McKie, V., Carl, E., Nichols, F.T., Liu, J.C., McKie, K., Clary, A., Alpha thalassemia and stroke risk in sickle cell anemia (1994) Am J Hematol, 45, pp. 279-282Adams, J.G., Benjamin, L., Fryd, S., Gillette, P., Gilman, J., Hellman-Erlingsson, S., Hsu, H., Wrightstone, R., Gender and haplotype effects upon hematological and clinical manifestations of sickle cell anemia (1992) Clin Res, 40, p. 378. , abstractPowars, D.R., Chan, L., Schroeder, W.A., βS-gene-cluster haplotypes in sickle cell anemia: Clinical implications (1990) Am J Pediatr Hematol Oncol, 12, pp. 367-374Koshy, M., Entsuah, R., Koranda, A., Kraus, A.P., Johnson, R., Bellvue, R., Flournoy-Gill, Z., Levy, P., Leg ulcers in patients with sickle cell disease (1989) Blood, 74, pp. 1403-1408Powars, D.R., Chan, L., Schroeder, W.A., The influence of fetal hemoglobin on the clinical expression of sickle cell anemia (1989) Ann NY Acad Sci, 565, pp. 262-27

Haptoglobin polymorphism in a HIV‐1 seropositive Brazilian population

BACKGROUND: Haptoglobin (Hp) is a plasma protein with antioxidant and immunomodulatory properties. Three main genotypes/phenotypes (Hp1‐1, Hp2‐1, Hp2‐2) show distinctive efficiencies in their activities and have been related to susceptibility and outcome in different diseases, including HIV infection. OBJECTIVE: To compare Hp genotype distribution between HIV‐1 seropositive patients and healthy controls. METHODS: 387 Brazilian HIV‐1 seropositive patients, subclassified as A, B, and C according to the Centers for Disease Control, were compared with 142 healthy controls. The influence of the polymorphism on iron status (serum iron, ferritin, transferrin, transferrin saturation), acute phase proteins (Hp, C reactive protein, fibrinogen, albumin), the HIV‐1 viral load, and CD4+ T lymphocyte counts was examined. RESULTS: Apart from finding lower Hp concentrations among individuals with genotype Hp2‐2, no other significant difference was observed. CONCLUSIONS: No association was found between Hp genotype and either HIV status or indices of HIV progression

SICKLE-CELL DISEASE in A BRAZILIAN POPULATION FROM SAO-PAULO - A STUDY of the BETA(S) HAPLOTYPES

In this study we have determined the frequency of beta(s) haplotypes in a Brazilian sickle cell disease population from São Paulo, Brazil, by analyzing sequence variations in the immediate 5' flanking and second intervening sequence (IVSII) regions of the gamma globin genes. This association between sequence differences and beta(s) haplotype backgrounds was determined by screening genomic DNA samples using dot blot analysis of polymerase chain reaction products. We studied 148 beta(s) chromosomes, and found that haplotype 20 (CAR or Bantu) signif icantly predominated in this population. This is in agreement with the findings of the historical Portuguese Atlantic slaveMED COLL GEORGIA,DEPT BIOCHEM & MOLEC BIOL,AUGUSTA,GA 30912UNICAMP,SCH MED SCI,DEPT CLIN MED,CAMPINAS,SP,BRAZILESCOLA PAULISTA MED,São Paulo,BRAZILESCOLA PAULISTA MED,São Paulo,BRAZILWeb of Scienc