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

作者：Moradkhani Kamran; Prehu Claude; Old John; Henderson Shirley; Balamitsa Vera; Luo Hong Yuan; Poon Man Chiu; Chui David H K; Wajcman Henri; Patrinos George P^*

来源：Annals of Hematology, 2009, 88(6): 535-543.

DOI：10.1007/s00277-008-0624-3

• alpha-Globin genes
• Paralogues
• Gene conversion
• Hemoglobin variants
• Mutations

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 (alpha 2) is higher than the percentage of hemoglobin variants due to the same HBA1 gene mutation (alpha 1) and that the alpha 2/alpha 1 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.

• 出版日期2009-6