Identification of deletion and triple α‐globin gene haplotypes in the montreal β‐thalassemia screening program: Implications for genetic medicine

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Abstract
We obtained blood samples in a screening program designed to detect β‐thalassemia heterozygotes in Montreal; additional samples were obtained from referred persons. We analyzed DNA for variant numbers of α‐globin genes, notably the α‐thalassemia2(‐ α/), α‐thalassemia1, (– –/), and triplicated ζ‐globin gene (ααα/) haplotypes using restriction enzymes and probes for α‐globin and α‐globin gene sequences. We estimated the numbers of Montreal residents of Italian and Greek ethnic origin with –α/αα genotype. Thus, 4.3% of Italians and 1.5% of Greeks, or about 7,500 persons, are estimated to be α‐thalassemia2, trait (silent carriers), largely (80%) in the –α3.7/type I form. The triplicated α‐globin gene haplotype was also found. The risk of a severe (α‐thalassemia1) phenotype associated with inheritance of – –;/αα or –α/ –α genotypes was low and was found predominantly in this study, in persons of Asian ethnic origin. The sample of Asians was too small to estimate carrier frequencies; however, based on results from the β‐thalassemia screening program, we estimated that about 4% of Asians (about 1,300 persons) in Montreal are α‐thalassemia carriers. We identified persons heterozygous for both β‐thalassemia and α‐thalassemia mutations. In these double heterozygotes, the effect of the triplicated α‐globin gene was to make the erythrocyte parameters used for screening (MCV and %HbA2) more deviant from normal whereas deletion of 2 α‐globin genes tended to normalize the erythrocyte values. These findings have implications for the screening program and reproductive counseling.