Mutations in the Paralogous Human α-globin Genes Yielding Identical Hemoglobin Variants
Chui, David H. K.
Patrinos, George P.
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CitationMoradkhani, Kamran, Claude Préhu, John Old, Shirley Henderson, Vera Balamitsa, Hong-Yuan Luo, Man-Chiu Poon, David H. K. Chui, Henri Wajcman, George P. Patrinos. "Mutations in the paralogous human α-globin genes yielding identical hemoglobin variants" Annals of Hematology 88(6): 535-543. (2008)
The human α-globin genes are paralogues, sharing a high degree of DNA sequence similarity and producing an identical α-globin chain. Over half of the α-globin structural variants reported to date are only characterized at the amino acid level. It is likely that a fraction of these variants, with phenotypes differing from one observation to another, may be due to the same mutation but on a different α-globin gene. There have been very few previous examples of hemoglobin variants that can be found at both HBA1 and HBA2 genes. Here, we report the results of a systematic multicenter study in a large multiethnic population to identify such variants and to analyze their differences from a functional and evolutionary perspective. We identified 14 different Hb variants resulting from identical mutations on either one of the two human α-globin paralogue genes. We also showed that the average percentage of hemoglobin variants due to a HBA2 gene mutation (α2) is higher than the percentage of hemoglobin variants due to the same HBA1 gene mutation (α1) and that the α2/α1 ratio varied between variants. These α-globin chain variants have most likely occurred via recurrent mutations, gene conversion events, or both. Based on these data, we propose a nomenclature for hemoglobin variants that fall into this category. ELECTRONIC SUPPLEMENTARY MATERIAL. The online version of this article (doi:10.1007/s00277-008-0624-3) contains supplementary material, which is available to authorized users.