Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia.

Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out.

[1]  J. Clegg,et al.  Molecular Basis of Thalassaemia , 1975 .

[2]  R. Williamson,et al.  Human globin gene analysis for a patient with beta-o/delta beta-thalassemia. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Clegg,et al.  Homozygous beta thalassaemia in Liberia. , 1975, Journal of medical genetics.

[4]  E. Schwartz,et al.  Globin Synthesis in the Jamaican Negro with Beta‐Thalassaemia , 1974, British journal of haematology.

[5]  J. A. Easton.  The Thalassaemia Syndromes (2nd edn.) , 1973 .

[6]  P. Wasi.  IS THE HUMAN GLOBIN α‐CHAIN LOCUS DUPLICATED? , 1973, British journal of haematology.

[7]  W. Nance,et al.  Further evidence for close linkage of the Hb-beta and Hb-delta loci in man. , 1969, Journal of medical genetics.

[8]  T. Huisman,et al.  Studies on the heterogeneity of hemoglobin. 13. Chromatography of various human and animal hemoglobin types on DEAE-Sephadex. , 1968, Journal of chromatography.

[9]  D. Weatherall.  The thalassemias. , 1967, Progress in medical genetics.

[10]  H. Pearson,et al.  HUMAN HEMOGLOBIN GENE LINKAGE: REPORT OF A FAMILY WITH HEMOGLOBIN B2, HEMOGLOBIN S, AND BETA THALASSEMIA, INCLUDING A PROBABLE CROSSOVER BETWEEN THALASSEMIA AND DELTA LOCI. , 1965, American journal of human genetics.

[11]  W. N. Bell,et al.  Hb-S, beta thalassemia and Hb-A-2 (B-2) in a family with evidence of a crossover between beta and delta loci. , 1965, Acta genetica et statistica medica.

[12]  D. Weatherall.  Biochemical Phenotypes of Thalassemia in the American Negro Population * , 1964, Annals of the New York Academy of Sciences.

[13]  S. Boyer,et al.  FURTHER EVIDENCE OF LINKAGE BETWEEN THE BETA AND DELTA LOCI GOVERNING HUMAN HEMOGLOBIN AND THE POPULATION DYNAMICS OF LINKED GENES. , 1963, American journal of human genetics.

[14]  R. F. Taylor,et al.  Improved rapid methods for the determination of iron content and binding capacity of serum , 1962, Journal of clinical pathology.

[15]  K. Punt,et al.  Thalassemia minor associated with hemoglobin-B2 heterozygosity. A family report. , 1961, Blood.

[16]  K. Betke,et al.  Estimation of Small Percentages of Fœtal Hæmoglobin , 1959, Nature.

[17]  R. Ceppellini.  [Normal slow hemoglobin A2; its relation with a new slow hemoglobin B2 fraction and its importance for the recognition of thalassemic variants which occur in families with thalassemia media and hemoglobinopathy H]. , 1959, Acta geneticae medicae et gemellologiae.