ABSTRACT
We used restriction endonuclease analysis to determine the incidence of alpha-thalassemia in two Mediterranean islands. In a random population sample, the gene frequency of deletion-type alpha-thalassemia-2 (-alpha) was 0.18 in Sardinians and 0.07 in Greek Cypriots. All cases were the rightward crossover type. From these frequencies and the known incidence of hemoglobin-H disease in these populations, we calculated the frequency of the alpha-thalassemia-1 genotype (--) and determined that it was low. We also found that beta-thalassemia homozygotes in sardinia have a higher incidence of alpha-thalassemia than normals and beta thalassemia heterozygotes because a significantly greater number of these homozygotes are also homozygous for the alpha-thalassemia-2 lesion. These findings support the theory that coinheritance of alpha-thalassemia mitigates the severity of beta-thalassemia and suggest that the protection is most pronounced when two alpha-globin genes are deleted.
Subject(s)
Thalassemia/genetics , Cyprus , Gene Frequency , Heterozygote , Homozygote , Humans , Italy , Thalassemia/epidemiologyABSTRACT
Restriction endonuclease mapping of nondeletion alpha-thalassemia determinants from a variety of racial groups showed no detectable abnormalities within a 40-kilobase region of the zeta-alpha globin gene cluster. By using a zeta-specific probe, we defined three different types of interactions that give rise to Hb H disease, each involving a nondeletion alpha-thalassemia haplotype. mRNA analysis showed further diversity within these groups, indicating that there are at least three nondeletion determinations.
Subject(s)
Hemoglobin H/genetics , Hemoglobins, Abnormal/genetics , Thalassemia/genetics , Chromosome Deletion , Chromosome Mapping , DNA Restriction Enzymes , Genes , Genes, Regulator , Genetic Linkage , Humans , Molecular Weight , RNA, Messenger/geneticsABSTRACT
A programme for the prevention of beta-homozygous thalassaemia has been operating in Cyprus from 1973. From 1976 there has been an increasing gap between the number of homozygotes born and the number expected, calculated as 1 in 135 of the total births. In 1978 23 homozygotes are known to have been born compared with 71 expected, and in 1979, 18 compared with 77 expected. All cases may not have yet to come to notice. the programme consists of public education, population screening, genetic counseling, and antenatal diagnosis.
Subject(s)
Thalassemia/prevention & control , Cyprus , Female , Genetic Carrier Screening , Genetic Counseling , Health Education , Humans , Male , Mass Screening , Prenatal Diagnosis , Thalassemia/geneticsABSTRACT
We have identified 12 individuals who are heterozygous for a chromosome with three alpha-globin genes. We determined the presence of the third alpha-globin locus by restriction endonuclease digestion and hybridization with alpha-globin cDNA probes. The three alpha-globin loci resided in an elongated fragment on digestion with EcoRI, BamHI, and Xba I, and the third locus was present in an additional 3.7-kilobase fragment on digestion with Hpa I, Sac I, and Bgl II. The locations of the restriction sites are compatible with a nonhomologous crossover mechanism producing the triple alpha loci. The frequency of the triple alpha loci was 0.0036 in American blacks and less than 0.004 in Sardinians, but was higher in Greek Crypriots (0.05). Individuals with five alpha-globin genes (alpha alpha/alpha alpha alpha) apparently showed no clinical or hematologic abnormalities.
Subject(s)
Genes , Globins/genetics , Black People , Cyprus/ethnology , Gene Frequency , Genetic Linkage , Hemoglobin A/biosynthesis , Humans , Recombination, GeneticABSTRACT
We investigated the molecular basis of hemoglobin-H disease by hybridization and restriction endonuclease mapping of the DNA in the Mediterranean populations. Of the 12 patients studied from Cyprus and Sardinia, 8 had the typical deletion defect with a single remaining alpha-globin gene. The nondeletion type of alpha-thalassemia was found in 3, and a "dysfunctional" gene in one. We conclude that the predominant cause of alpha-thalassemia in these populations is gene deletion.
