Summary
We have identified a new stable abnormal hemoglobin called Hb Valletta, which is characterized by a Thr→Pro substitution at position 87 of the β chain. This mutation was found to be linked to that of the γ chain variant Hb F-Malta-I with a His→Arg mutation at position 117 of the Gγ chain. Both variants were detected in the blood samples of 34 Maltese and two Italian new-born babies with isoelectrofocusing and reversed phase high performance liquid chromatography. Similar analyses of cord blood from 388 additional Maltese newborns failed to identify either one of these two variants. Additional analyses of 353 Maltese adults (including 39 β-thalassemia heterozygotes) resulted in the detection of two adult Hb Valletta heterozygotes. Dot-blot hybridization analyses of amplified DNA with a probe specific for the Gγ-F-Malta-I variant showed that both also carried that mutation. These results show close linkage of the mutant forms of the Gγ- and β-globin genes, 27–28 kb apart, and a failure to identify chromosomes with either the Hb F-Malta-I mutation alone or with the Hb Valletta mutation alone, indicating a low recombination frequency.
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References
Antonarakis SE, Boehm CD, Giardina PJV, Kazazian HH Jr (1982) Nonrandom association of polymorphic restriction sites in the β-globin gene cluster. Proc Natl Acad Sci USA 79:137–141
Bannister WH, Grech JL, Plese CF, Smith LL, Barton BP, Wilson JB, Reynolds CA, Huisman THJ (1972) Hemoglobin St Luke's or α295Arg(G2)β2. Eur J Biochem 29:301–307
Blouquit Y, Arous N, Lena D, Delanoe-Garin J, Lacombe C, Bardakdjian J, Vovan L, Orsini A, Rosa J, Galacteros F (1984) Hb Marseille [α2β2 N methionyl-2(NA2)His→Pro]: a new β chain variant having an extended N-terminus. FEBS Lett 178: 315–318
Bunn HF, Forget BG (1986) Hemoglobin: molecular, genetic and clinical aspects. Saunders, Philadelphia
Cauchi MN, Clegg JB, Weatherall DJ (1969) Haemoglobin F (Malta): a new foetal haemoglobin variant with a high incidence in Maltese infants. Nature 223:311–313
Chang JY, Brauer D, Wittmann-Liebold B (1978) Micro-sequence analysis of peptides and proteins using 4-NN-dimethylaminoazobenzene 4′-isothiocyanate/phenyl-isothiocyanate double coupling method. FEBS Lett 93:205–214
Gonzalez-Redondo JM, Stoming TA, Lanclos KD, Gu YC, Kutlar A, Nakatsuji T, Deng B, Han IS, McKie VC, Huisman THJ (1988) Clinical and genetic heterogeneity in Black patients with homozygous β-thalassemia from the Southeastern United States. Blood 72:1007–1014
Huisman THJ (1987) The separation of hemoglobins and hemoglobin chains by high performance liquid chromatography. J Chromatogr 418:277–304
Huisman THJ, Jonxis JHP (1977) The hemoglobinoathies techniques of identification. (Clinical and biochemical analysis, vol 6) Dekker, New York
International Hemoglobin Information Center Variant List (1989) Hemoglobin 13:223–297
Kutlar F, Kutlar A, Huisman THJ (1986) Separation of normal and abnormal hemoglobin chains by reversed-phase high performance liquid chromatography. J Chromatogr 357:147–153
Poncz M, Solowiejczyk D, Harpel B, Mory Y, Schwartz E, Surrey S (1982) Construction of human gene libraries from small amounts of peripheral blood: analysis of β-like globin genes. Hemoglobin 6:27–36
Righetti PG (1986) Practical application of isoelectricfocusing in hemoglobin separation and identification. In: Huisman THJ (ed) The hemoglobinopathies. (Methods in hematology series, vol 15) Churchill Livingstone, Edinburgh, pp 47–70
Schroeder WA, Huisman THJ (1980) The chromatography of hemoglobin. (Clinical and biochemical analysis, vol 9) Dekker, New York
Semenza GL, Malladi P, Surrey S, Delgrosso K, Poncs M, Schwartz E (1984) Detection of a novel DNA polymorphism in the β-globin gene cluster. J Biol Chem 259:6045–6048
Shelton JB, Shelton JR, Schroeder WA (1984) High performance liquid chromatographic separation of globin chains on a largepore C4 column. J Chromatogr 7:1969–1977
Wilkinson T, Ching Geh Chua, Carrell RW, Robin H, Exner T, Kit Ming Lee, Kronenberg H (1975) A new haemoglobin variant, Haemoglobin Camperdown β104(G6) arginine→ serine. Biochim Biophys Acta 393:195–200
Wilson JB, Lam H, Pravatmuang P, Huisman THJ (1979) Separation of tryptic peptides of normal and abnormal α, β, γ, and δ hemoglobin chains by high-performance liquid chromatography. J Chromatogr 179:271–290
Yang KG, Kutlar F, George E, Wilson JB, Kutlar A, Stoming TA, Gonzalez-Redondo JM, Huisman THJ (1989) Molecular characterization of β-globin gene mutations in Malay patients with Hb E-β-thalassaemia and thalassaemia major. Br J Haematol 72:72–80
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Kutlar, F., Felice, A.E., Grech, J.L. et al. The linkage of Hb Valletta [α2β287(F3)Thr→Pro] and Hb F-Malta-I [α2 Gγ2117(G19)His→Arg] in the Maltese population. Hum Genet 86, 591–594 (1991). https://doi.org/10.1007/BF00201546
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DOI: https://doi.org/10.1007/BF00201546