title: Identification of deletion and triple alpha-globin gene haplotypes in the Montreal beta-thalassemia screening program: implications for genetic medicine.
abstract: We obtained blood samples in a screening program designed to detect beta-thalassemia heterozygotes in Montreal; additional samples were obtained from referred persons. We analyzed DNA for variant numbers of alpha-globin genes, notably the alpha-thalassemia2 (-alpha/), alpha-thalassemia1, (- -/), and triplicated alpha-globin gene (alpha alpha alpha/) haplotypes using restriction enzymes and probes for alpha-globin and zeta-globin gene sequences. We estimated the numbers of Montreal residents of Italian and Greek ethnic origin with -alpha/alpha alpha genotype. Thus, 4.3% of Italians and 1.5% of Greeks, or about 7,500 persons, are estimated to be alpha-thalassemia2, trait (silent carriers), largely (80%) in the -alpha 3.7/type I form. The triplicated alpha-globin gene haplotype was also found. The risk of a severe (alpha-thalassemia1) phenotype associated with inheritance of - -/alpha alpha or -alpha/-alpha 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 beta-thalassemia screening program, we estimated that about 4% of Asians (about 1,300 persons) in Montreal are alpha-thalassemia carriers. We identified persons heterozygous for both beta-thalassemia and alpha-thalassemia mutations. In these double heterozygotes, the effect of the triplicated alpha-globin gene was to make the erythrocyte parameters used for screening (MCV and %HbA2) more deviant from normal whereas deletion of 2 alpha-globin genes tended to normalize the erythrocyte values. These findings have implications for the screening program and reproductive counseling.
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: B R
authors.initials: BR
authors.lastname: Akerman
authors.forename: T M
authors.initials: TM
authors.lastname: Fujiwara
authors.forename: G A
authors.initials: GA
authors.lastname: Lancaster
authors.forename: K
authors.initials: K
authors.lastname: Morgan
authors.forename: C R
authors.initials: CR
authors.lastname: Scriver
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004247:DNA / Q000032:analysis; D004909:Erythrocyte Indices / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006443:Hemoglobin A2 / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D010641:Phenotype; D011792:Quebec / Q000453:epidemiology; D013789:Thalassemia / Q000208:ethnology / Q000235:genetics*
chemical_list: D005914:Globins; D004247:DNA; D006443:Hemoglobin A2