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ALSO KNOWN AS | |
G-Knoxville; Stanleyville-I, D-Washington; D-St. Louis; G-Bristol; G-Azakouli; D-Baltimore | |
CONTACT | |
External | |
HEMATOLOGY | |
No hematological abnormalities in the heterozygote due to the presence of the Hb G-Philadelphia anomaly | |
ELECTROPHORESIS | |
Hb X and Hb A separate at alkaline pH but not at acidic pH; moves to the position of Hb S on paper, starch gel, and cellulose acetate; excellent separation on IEF | |
CHROMATOGRAPHY | |
Hb X separates from Hb A by both cation and anion exchange chromatography | |
STRUCTURE STUDIES | |
Tryptic digestion; separation of peptides by fingerprinting or by cation exchange chromatography or by reversed phase HPLC; amino acid analysis | |
DNA ANALYSES | |
Two mutations have been detected (Refs. 9,10); 1) AAC->AAG on a chromosome that carries the 3.7 kb deletion (-alpha3.7/ on the alpha2alpha1 hybrid gene); 2) AAC->AAA of the alpha2 gene of a chromosome with a normal complement of two alpha-globin genes (alphaGalpha/) | |
FUNCTIONAL STUDIES | |
Normal | |
STABILITY | |
Stable | |
OCCURRENCE | |
This is the most common alpha chain variant in Blacks; also present in Italians from Northern Italy and Sardinia, and in a few Chinese families | |
OTHER INFORMATION | |
1) Hb G-Philadelphia in Blacks is present on a chromosome with the 3.7 kb deletion (alpha-thal-2); the quantity of Hb G in such individuals varies between 30-35%. 2) When an alpha-thal-2 (3.7 kb deletion) occurs in trans (-alphaG/-alpha) the quantity of Hb G is increased to ~45%; these individuals have a distinct microcytosis and hypochromia (alpha-thal-2 homozygotes). 3) Homozygosity for Hb G-Philadelphia (-alphaG/-alphaG) results in 100% G-Philadelphia; these individ-uals also have a distinct microcytosis; hypochromia (alpha-thal-2 homozygotes). 4) Hb G-Philadelphia in combination with an alpha-thal-1, although extremely rare, results in an Hb H disease (-alphaG/--) and 100% G-Philadelphia. 5) The occurrence of Hb G-Philadelphia (-alphaG/alphaalpha) with Hb S and/or Hb C is rather common. 6) Italians with Hb G-Philadelphia have a full complement of four alpha-globin genes (alphaGalpha/alphaalpha) and 20-25% G-Philadelphia; no hematological abnormalities are found | |
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REFERENCES |
1. | |
Baglioni, C. and Ingram, V.M.: Biochim. Biophys. Acta, 48:253, 1961. | |
2. | |
Minnich, V., Cordonnier, J.K., Williams, W.J., and Moore, C.V.: Blood, 19:137, 1962. | |
3. | |
Dance, N., Huehns, E.R., and Shooter, E.M.: Biochim. Biophys. Acta, 86:144, 1964. | |
4. | |
Chernoff, A.I. and Pettit, N., Jr.: Biochim. Biophys. Acta, 97:47, 1965. | |
5. | |
Bowman, B., Barnett, D.R., Hodgkinson, K.T., and Schneider, R.G.: Nature, 211:1305, 1966. | |
6. | |
Blackwell, R.Q., Wang, C.L., Liu, C-S., and Shih, T-B.: Vox Sang., 25:184, 1973. | |
7. | |
Rucknagel, D.L. and Rising, J.A.: Am. J. Med., 59:53, 1976. | |
8. | |
Milner, P.F. and Huisman, T.H.J.: Br. J. Haematol., 34:207, 1976. | |
9. | |
Molchanova, T.P., Pobedimskaya, D.D., and Huisman, T.H.J.: Br. J. Haematol., 88:300, 1994. | |
10. | |
Molchanova, T.P., Pobedimskaya, D.D., Ye, Z., and Huisman, T.H.J.: Am. J. Hematol., 45:345, 1994. | |