Molecular studies performed in Portuguese and Brazilian cases of hemoglobin Porto Alegre [β9 Ser→Cys]Cy's revealed that the mutation is in association with the Mediterranean haplotype I and framework 1 and that it is also in cis with an undescribed intragenic polymorphism (codon 27, GCC→GCT). Based upon these findings, and reinforced by historical data, we suggest that hemoglobin Porto Alegre originated from a single mutational event in the Portuguese population and was then spread to South America, namely to Brazil.89810091010Tondo, C.V., Salzano, F.M., Rucknagel, D.L., Hemoglobin Porto Alegre, a possible polymer of normal hemoglobin in a Caucasian Brazilian family (1963) Am J Hum Genet, 15, pp. 265-279Seid-Akhavan, M., Ayres, M., Salzano, F.M., Winter, W.P., Rucknagel, D.L., Two more examples of Hb Porto Alegre, α-2 β-2 9 Ser leads to Cys in Belem, Brazil (1973) Hum Hered, 23, pp. 175-181Gonçalves, M.S., Sonati, M.F., Kimura, M., Arruda, V.R., Costa, F.F., Netchtman, J.F., Association of Hb Santa Ana [a2b288(F4)Leu_Pro] and Hb Porto Alegre [α2β29(A6) Ser_Cys] in a Brazilian female (1994) Hemoglobin, 18, pp. 235-239Martinez, G., Lima, F., Wade, M., Estrada, M., Colombo, B., Heredero, L., Hemoglobin Porto Alegre in a Cuban family (1977) J Med Genet, 14, pp. 422-425Malcorra-Azpiazu, J.J., Wilson, J.B., Molchanova, T.P., Pobedimskaya, D.D., Huisman, T.H.J., Hb Porto Alegre or α2β29(A6) Ser_Cys in unrelated families of the Canary Islands (1993) Hemoglobin, 17, pp. 457-461Leone, L., Monteleone, M., Gabutt, V., Amione, C., Reversed-phase high-performance liquid chromatography of human hemoglobin chains (1985) J Chromatography, 321, pp. 407-419Miller, S.A., Dykes, D.D., Polesky, H.F., A simple salting-out procedure for extracting DNA from human nucleated cells (1988) Nucleic Acids Res, 16, p. 1215Antonarakis, S.E., Kazazian Jr., H.H., Orkin, S.H., DNA polymorphism and molecular pathology of the human globin gene clusters (1985) Human Genetics, 69, pp. 1-14http://www.canaryforum.com/gc/historical.htmlDe Azevedo, T., Antropologia (1986) Encicliopédia Luso-Brasileira da Cultura, pp. 1818-1911. , Verbo editor. Lisboa/S̈o Paulo