Presence Of Allele α(lely) In An Amazonian Indian Population

Allele α(LELY) is a low-expression allele of the erythroid spectrin α- chain that is characterized by a C → G mutation at position α1857 in exon 40 and a C → T (nt -12) mutation in intron 45. This second mutation is probably responsible for the partial skipping of exon 46. This exon is essential for the nucleation of the α-chains by the β-chains during erythropoeisis. Although allele α(LELY) remains asymptomatic in both heterozygotes and homozygotes, it enhances the expression of deleterious α- alleles that occur and, as such, has clinical importance. In this study, the frequency of allele α(LELY) was estimated in two ethnically different Brazilian populations: a random sample of blood donors from Campinas, a city located in Sao Paulo State, in the southeastern region of Brazil, and a sample of Parakana Indians (Tupi tribe), a very isolated population with a high degree of inbreeding. The frequency of allele α(LELY) in the blood donor's sample (n = 54) was 24.1% whereas in the indigenous sample (n = 41), it was 15.9%. These frequencies were not significantly different at the 5% level (χ2 = 1.931). Similarly, when the frequencies of our samples were compared with those of the four ethnic groups studied by Marechal et al. [Br J Haematol 90:553-556, 1995], no significant differences were found at the 5% level (χ2 = 6.686). These results suggest that allele α(LELY) is a very ancient allele since it occurs with a relatively uniform and high frequency in all human ethnic groups studied so far. These findings confirm the importance of allele α(LELY) in influencing the expression of deleterious α-spectrin alleles. To our knowledge, these are the first data concerning allele α(LELY) in native Americans.573212214Alloisio, N., Morlé, L., Maréchal, J., Roux, A.-F., Ducluzeau, M.-T., Guetarni, D., Pothier, B., Delaunay, J., SpαV/41: A common spectrin polymorphism at the αIV-αV domain junction (1991) J Clin Invest, 87, pp. 2169-2177Wilmotte, R., Maréchal, J., Morlé, L., Baklouti, F., Philippe, N., Kastally, R., Kotula, L., Alloisio, N., Low expression allele αLELY of red cell spectrin is associated with mutations in exon 40 (αV/41 polymor phism) and intron 45 and with partial skipping of exon 46 (1993) J Clin Invest, 91, pp. 2091-2096Randon, J., Boulanger, L., Maréchal, J., Garbarz, M., Vallier, A., Ribeiro, L., Tamagnini, G., Delaunay, J., A variant of spectrin low-expression allele alpha LELY carrying a hereditary elliptocytosis mutation in codon 28 (1994) Br J Haematol, 88, pp. 534-540Maréchal, J., Wilmotte, R., Kanzaki, A., Dhermy, D., Garbarz, M., Galand, C., Tang, T.K., Delaunay, J., Ethnic distribution of allele αLELY, a low-expression allele of red cell spectrin α-gene (1995) Br J Haematol, 90, pp. 553-556Curtin, P.D., (1969) The Atlantic Slave Trade: A Census, , Milwaukee: University of Wisconsin PressGibbons, A., Geneticists trace the DNA trail of the 1st Americans (1993) Science, 259, pp. 312-313Black, F.L., Salzano, F.M., Layrisse, Z., Franco, M.H.L.P., Harris, N.S., Weimer, T.A., Restriction and persistence of polymorphisms of HLA and other blood genetic traits in the Parakanã Indians of Brazil (1981) Am J Phys Anthropol, 52, pp. 119-132Saiki, R.K., Geelfond, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.T., Mullis, K.B., Erlich, H.A., Primer-directed enzymatic amplification of DNA with a thermostable DNA polyinerase (1988) Science, 239, pp. 487-491Gallagher, P.G., Forget, B.G., Spectrin St Louis and the αLELY allele (1994) Blood, 84, pp. 1684-1686Saad, S.T.O., Salles, T.S.I., Carvalho, M.H.M., Costa, F.F., Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Brazil (1997) Hum Hered, 47, pp. 17-21Neel, J.V., Salzano, F.M., Further studies on the Xavante Indians. X. Some hypotheses-generalizations resulting from these studies (1967) Am J Hum Genet, 19, pp. 554-574Chagnon, N.A., (1974) Studying the Yanomamo, , New York: Holt, Reinhart, Winsto

G6pd Sumare: A Novel Mutation In The G6pd Gene (1292 T →g) Associated With Chronic Nonspherocyfic Anemia

[No abstract available]103245247Beutler, E., Red cell metabolism (1975) A Manual of Biochemical Methods, 2nd Ed., , Grune & StrattonBeutler, E., Glucose-6-phosphate dehydrogenase deficiency (1991) N Engl J Med, 324, pp. 169-174Beutler, E., The molecular biology of G6PD variants and other red cell enzyme defects (1992) Annu Rev Med, 43, pp. 47-59Beutler, E., G6PD deficiency (1994) Blood, 84, pp. 3613-3636Beutler, E., Kuhl, W., The NT 1311 Polymorphism of G-6-PD Mediterranean mutation may originated independently in Europe and Asia (1990) Hum Genet, 47, pp. 1008-1012D'Urso, M., Luzzatto, L., Perroni, L., Ciccodicola, A., Gentile, G., Peluso, I., Persico, M.G., Vulliamy, T.J., An extensive search for RFLP in the human glucose-6-phosphate dehydrogenase locus revealed a silent mutation in the coding sequence (1988) Am J Hum Genet, 42, pp. 735-741Fey, M.F., Wainscoat, J.S., Mukwala, E.C., Falusi, A.C., Vulliamy, T.J., Luzzato, L., A Pvu II restriction fragment length polymorphism of the glucose-6-phosphate dehydrogenase gene is an African-specific marker (1993) Hum Genet, 84, pp. 471-472Jeffery, J., Persson, B., Wood, I., Bergman, T., Jeffery, R., Jörnvall, H., Glucose-6-phosphate dehydrogenase: Structure-function relationships and the Pichia Jadinii enzyme structure (1993) Eur J Biochem, 212, pp. 41-4

Red Cell Membrane Protein Abnormalities In Hereditary Spherocytosis In Brazil

We studied 14 kindred and nine unrelated patients from southeastern Brazil with the typical form of hereditary spherocytosis. Diagnosis was made on the basis of clinical features, presence of spherocytes on the peripheral blood smears and an abnormal osmotic fragility test. By densitometric tracing of SDS-PAGE stained by Coomassie blue, we detected isolated deficiency of spectrin in 39% of our patients, combined spectrin and ankyrin deficiency in 13%, and deficiency of band 3 in 13%. One of our patients presented ankyrin deficiency without spectrin reduction. Our data suggest that, despite ethnic differences among the Brazilian and European or North-American populations, these biochemical abnormalities in HS patients may be similar.88229529