The molecular basis of alpha-thalassemia in Thailand.
Alpha thalassemia is the most common single gene mutation worldwide. In Thailand there exists 15-30% alpha-thalassemia carriers distributed throughout the country. DNA analysis by Southern blot hybridization reveals that the two major alpha-thalassemia alleles, alpha-thalassemia 1 and alpha-thalassemia 2 have different extents of alpha-globin gene deletion. In alpha-thalassemia 1, approximately 20 kb of DNA including the two linked alpha 1-and alpha 2-genes are removed and only the alpha-globin gene is intact. Total deletion of the alpha-globin gene cluster is rarely observed. In contrast, only one alpha-globin gene is deleted in alpha-thalassemia 2 of which two types have been detected, one involving a deletion of 4.2 kb of DNA (leftward type, -alpha 4.2) and another of 3.7 kb (rightward type, -alpha 3.7); the latter being more common than the former in Thailand. Compound heterozygosity for alpha-thalassemia 1 and alpha-thalassemia 2 results in HbH disease while homozygosity for alpha-thalassemia 1 leads to Hb Bart's hydrops fetalis, the most severe form of thalassemic disease. Three alpha-thalassemic hemoglobinopathies have been detected in Thailand, two of which produce a remarkable reduction in gene product. Upon interacting with alpha-thalassemia 1 gene they can lead to HbH disease. The most common in this group is Hb Constant Spring which arises from mutation of the termination codon in the alpha 2-gene resulting in an elongation of the alpha-globin chain.(ABSTRACT TRUNCATED AT 250 WORDS)
Winichagoon
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Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Fucharoen
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Wasi
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D001797:Blood Protein Electrophoresis; D015139:Blotting, Southern; D004909:Erythrocyte Indices; D017353:Gene Deletion; D005787:Gene Frequency; D005914:Globins / Q000235:genetics*; D006447:Hemoglobin H; D006453:Hemoglobinopathies / Q000151:congenital / Q000453:epidemiology / Q000517:prevention & control; D006455:Hemoglobins, Abnormal; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015160:Hydrops Fetalis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D007231:Infant, Newborn; D008403:Mass Screening; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011296:Prenatal Diagnosis; D013785:Thailand / Q000453:epidemiology; D017085:alpha-Thalassemia / Q000145:classification / Q000453:epidemiology / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D005914:Globins; D006447:Hemoglobin H; C030448:hemoglobin Bart's