Mutations in the paralogous human α-globin genes yielding identical hemoglobin variants

Kamran Moradkhani (1, 2) , Claude Préhu (1, 2) , John Old (3) , Shirley Henderson (1) , Vera Balamitsa (4) , Hong-Yuan Luo (5) , Man-Chiu Poon (6) , David H. K. Chui (1) , Henri Wajcman (1, 2) , George P. Patrinos (7)

1 Service de Biochimie [Mondor]
2 IMRB - Institut Mondor de recherche biomédicale
3 National Haemoglobinopathy Reference Laboratory
4 Unit for Prevention of Thalassemia
5 Departments of Medicine, Pathology and Laboratory Medicine
6 Departments of Medicine and Pediatrics
7 MGC-Department of Cell Biology and Genetics

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 and 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 gene mutation (α2) is higher than the percentage of hemoglobin variants due to the same 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.

Mots clés: α-Globin genes; Paralogues; Gene conversion; Hemoglobin variants; Mutations

Kamran Moradkhani, Claude Préhu, John Old, Shirley Henderson, Vera Balamitsa, et al.. Mutations in the paralogous human α-globin genes yielding identical hemoglobin variants. Annals of Hematology, 2008, 88 (6), pp.535-543. ⟨10.1007/s00277-008-0624-3⟩. ⟨hal-00477986⟩