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

Ann Hematol. 2009 Jun;88(6):535-43. doi: 10.1007/s00277-008-0624-3. Epub 2008 Oct 16.


The human alpha-globin genes are paralogues, sharing a high degree of DNA sequence similarity and producing an identical alpha-globin chain. Over half of the alpha-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 alpha-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 alpha-globin paralogue genes. We also showed that the average percentage of hemoglobin variants due to a HBA2 gene mutation (alpha2) is higher than the percentage of hemoglobin variants due to the same HBA1 gene mutation (alpha1) and that the alpha2/alpha1 ratio varied between variants. These alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Variation / genetics*
  • Hemoglobins / genetics*
  • Humans
  • Mutation / genetics
  • Phenotype
  • alpha-Globins / genetics
  • alpha-Thalassemia / blood
  • alpha-Thalassemia / genetics


  • Hemoglobins
  • alpha-Globins