Mutations in the Paralogous Human Alpha-globin Genes Yielding Identical Hemoglobin Variants

Overview

Journal Ann Hematol

Specialty Hematology

Date 2008 Oct 17

PMID 18923834

Citations 12

Authors

Kamran Moradkhani

Claude Prehu

John Old

Shirley Henderson

Vera Balamitsa

Hong-Yuan Luo

Man-Chiu Poon

David H K Chui

Henri Wajcman

George P Patrinos

Affiliations

Soon will be listed here.

Abstract

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.

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