Identification of deletion and triple alpha-globin gene haplotypes in the Montreal beta-thalassemia screening program: implications for genetic medicine

Am J Med Genet. 1990 May;36(1):76-84. doi: 10.1002/ajmg.1320360115.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • DNA / analysis
  • Erythrocyte Indices / genetics
  • Female
  • Genetic Carrier Screening*
  • Genotype
  • Globins / genetics*
  • Haplotypes
  • Hemoglobin A2 / genetics
  • Humans
  • Infant
  • Male
  • Mass Screening
  • Middle Aged
  • Phenotype
  • Quebec / epidemiology
  • Thalassemia / ethnology
  • Thalassemia / genetics*

Substances

  • Globins
  • DNA
  • Hemoglobin A2