Hb Q-Thailand [α74(EF3)Asp→His]: Gene Organization, Molecular Structure, and DNA Diagnosis

Abstract

Hb Q-Thailand [α74(EF3)Asp→His] is often found in Thailand, China, and other Southeast Asian countries. The α-Q-Thailand gene is strongly linked to an α gene deletion and has important implications in the identification and diagnosis of hemoglobinopathies and thalassemias. The α-Q-Thailand mutation was previously mapped to the α1 gene in a study of Chinese patients. in this paper, a Thai patient with Hb Q-Thailand/Hb H disease and his mother were studied at the DNA level, and the gene organization of Hb Q-Thailand in the Thai patient was found to be the same as that of Chinese patients (i.e. the Hb Q-Thailand gene is located on the a1 gene of chromosome #16, while the -4.2 kb or leftward deletion involves the α2 gene). Also, the GACćcmutation proposed at codon 74, has been confirmed by DNA sequencing and a simple and accurate method for diagnosis of the Hb Q-Thailand variant has been developed based on restriction enzyme analysis. Since the GACĆC mutation generates new cutting sites for both restriction enzymes Apa LI and Hgi AI, polymerase chain reaction amplification of a specific region around codon 74, followed by digestion with these enzymes and agarose gel electrophoresis of the digested products, permits rapid and accurate identification of Hb Q-Thailand.