Skip to main content
SpringerLink
Log in

The Molecular Genetics of Thalassemia

  • Chapter
Advances in Human Genetics 11

Abstract

In the past few years analysis of the genetics and disorders of human hemoglobins has undergone a revolution as new research tools have provided the means to obtain long-sought-after answers regarding gene structure and function. Study of human hemoglobins and their disorders, particularly the thalassemia syndromes, is at the forefront of the interaction of new genetic technology and medicine. It offers the promise of understanding an entire class of diseases at the molecular level in detail totally unforeseen just a short time ago. In this review we will attempt to summarize recent approaches and findings in this rapidly moving area and illustrate how these studies may provide important models for the analysis of other human diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams, J. G., III, Boxer, L. A., Baehner, R. L., Forget, B. G., Tsistrakis, G. A., and Steinberg, M H., 1979, Hemoglobin Indianapolis (β112[G14]arginine), J. Clin Invest. 63:931–938.

    Article  PubMed  CAS  Google Scholar 

  • Alwine, J. C., Kemp, D. J., and Stark, G. R., 1977, Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes, Proc. Natl. Acad. Sci. USA 74:5350–5354.

    Article  PubMed  CAS  Google Scholar 

  • Amin, A. B., Pandya, N. L., Diwen, P. P., Darbre, P. D., Kattamis, C., Metaxaton-Mavromati, A., White, J. M., Wood, W. G., Clegg, J. B., and Weatherall, D. J., 1979, A comparison of the homozygous states for Gγ and GγAγδβ-thalassaemia, Br. J. Haematol. 43:537–548.

    Article  PubMed  CAS  Google Scholar 

  • Arnheim, N., and Kuehn, M., 1979, The genetic behavior of a cloned mouse ribosomal DNA segment mimics mouse ribosomal gene evolution, J. Mol. Biol. 134:743–765.

    Article  PubMed  CAS  Google Scholar 

  • Baralle, F. E., 1977, Complete nucleotide sequence of the 5’ noncoding region of human α- and β-globin mRNA, Cell 12:1085–1095.

    Article  PubMed  CAS  Google Scholar 

  • Bastos, R. N., and Aviv, H., 1977, Globin mRNA precursor molecules: Biosynthesis and processing in erythroid cells. Cell 11:641–650.

    Article  PubMed  CAS  Google Scholar 

  • Benoist, C., O’Hare, K., Breathnach, R., and Chambon, P., 1980, The ovalbumin gene-sequence of putative control regions, Nucleic Acids Res. 8:127–142.

    Article  PubMed  CAS  Google Scholar 

  • Benton, W. D., and Davis, R. W., 1977, Screening Xgt recombinant clones by hybridization to single plaques in situ, Science 196:180–182.

    Article  PubMed  CAS  Google Scholar 

  • Benz, E. J., Jr., Forget, B. G., Hillman, D. G., Cohen-Solal, M., Pritchard, J., Cavallesco, C., Prensky, W., and Housman, D., 1978, Variability in the amount of β-globin mRNA in β0-thalassemia, Cell 14:299–312.

    Article  PubMed  CAS  Google Scholar 

  • Bernards, R., and Flavell, R. A., 1980, Physical mapping of the globin gene deletion in hereditary persistence of foetal haemoglobin (HPFH), Nucleic Acids Res. 8:1521–1534.

    Article  PubMed  CAS  Google Scholar 

  • Bernards, R., Little, P. F. R., Annison, G., Williamson, R., and Flavell, R. A., 1979, Structure of the human Gγ-Aγ-δ-β-globin gene locus, Proc. Natl. Acad. Sci. USA 76:4827–4831.

    Article  PubMed  CAS  Google Scholar 

  • Blattner, F. R., Williams, B. G., Blechl, A. E., Thompson, K. D., Faber, H. E., Furlong, L. A., Grunwald, D. J., Kiefer, D. O., Moore, D. D., Schumm, J. W., Shelton, E. L., and Smithies, O., 1977, Charon phages: Safer derivatives of bacteriophage lambda for DNA cloning, Science 196:161–169.

    Article  PubMed  CAS  Google Scholar 

  • Blattner, F. R., Blechl, A. E., Denniston-Thompson, K., Faber, H. E., Richards, J. E., Slighton, J. L., Tucker, P. W., and Smithies, O., 1978, Cloning human fetal 7 globin and mouse α-type globin DNA: Preparation and screening of shotgun collections, Science 202:1279–1284.

    Article  PubMed  CAS  Google Scholar 

  • Breathnach, R., Benoist, C., O’Hare, K., Gannon, F., and Chambon, P., 1978, Ovalbumin gene: Evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries, Proc. Natl. Acad. Sci. USA 75:4853–4857.

    Article  PubMed  CAS  Google Scholar 

  • Chang, J. C., and Kan, Y. W., 1979, β°-thalassemia: A nonsense mutation in man. Proc. Natl. Acad. Sci. USA 76:2886–2889.

    Article  PubMed  CAS  Google Scholar 

  • Chang, J. C., Temple, G. F., Trecartin, R. F., and Kan, Y. W., 1979, Suppression of the nonsense mutation in homozygous ß°-thalassaemia, Nature (London) 281:602–603.

    Article  CAS  Google Scholar 

  • Clegg, J. B., and Tsevrenis, H., 1974, Haemoglobin Icaria, a new chain termination mutant which causes α-thalassaemia, Nature (London) 251:245–247.

    Article  CAS  Google Scholar 

  • Clegg, J. B., Weatherall, D. J., and Milner, P. F., 1971, Haemoglobin Constant Spring— a chain termination mutant?, Nature (London) 234:337–340.

    Article  CAS  Google Scholar 

  • Clegg, J. B., Metaxaton-Mavromati, A., Kattamis, C., Sofroniadou, K., Wood, W. G., and Weatherall, D. J., 1979, Occurrence of Gγ HbF in Greek HPFH: Analysis of heterozygotes and compound heterozygotes with β-thalassaemia, Br. J. Haematol. 43:521–536.

    Article  PubMed  CAS  Google Scholar 

  • Craik, C. S., Buchman, S. R., and Beychok, S., 1980, Characterization of globin domains: Heme binding to the central exon product, Proc. Natl. Acad. Sci. USA 77:1384–1388.

    Article  PubMed  CAS  Google Scholar 

  • Curtis, P. J., Mantei, N., van den Berg, J., and Weissmann, C., 1977, Presence of a putative 15S precursor to β-globin mRNA but not to α-globin mRNA in Friend cells, Proc. Natl. Acad. Sci. USA 74:3184–3188.

    Article  PubMed  CAS  Google Scholar 

  • Deisseroth, A., Nienhuis, A., Turner, P., Velez, R., Anderson, W. F., Ruddle, F., Laurence, J., Creagen, R., and Kucherlapati, R., 1977, Localization of the human α-globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization, Cell 12:205–218.

    Article  PubMed  CAS  Google Scholar 

  • Deisseroth, A., Nienhuis, A., Laurence, J., Giles, R., Turner, P., and Ruddle, F., 1978, Chromosomal location of human β-globin gene on human chromosome 11 in somatic cell hybrids, Proc. Natl. Acad. Sci. USA 75:1456–1460.

    Article  PubMed  CAS  Google Scholar 

  • Denhardt, D. T., 1966, A membrane-filter technique for the detection of complementary DNA, Biochem. Biophys. Res. Commun. 23:641–646.

    Article  PubMed  CAS  Google Scholar 

  • Dodgson, J. B., Strommer, J., and Engel, J. D., 1979, Isolation of the chicken β-globin gene and a linked embryonic β-like globin gene from a chicken DNA recombinant library, Cell 17:879–887.

    Article  PubMed  CAS  Google Scholar 

  • Doolittle, W. F., 1978, Genes in pieces, were they ever together?, Nature 272:581–582.

    Article  Google Scholar 

  • Dozy, A. M., Kan, Y. W., Embury, S. H., Mentzer, W. C., Wang, W. C., Lubin, B., Davis, J. R., Jr., and Koenig, H. M., 1979, α-Globin gene organisation in blacks precludes the severe form of α-thalassaemia, Nature (London) 280:605–607.

    Article  CAS  Google Scholar 

  • Duncan, C., Biro, P. A., Choudary, P. V., Elder, J. T., Wang, P. R. C., Forget, B. G., deRiel, J. K., and Weissman, S. M., 1979, RNA polymerase III transcriptional units are interspersed among human non-a globin genes, Proc. Natl. Acad. Sci. USA 76:5095–5099.

    Article  PubMed  CAS  Google Scholar 

  • Eaton, W. A., 1980, The relationship between coding sequences and function in haemoglobin, Nature (London) 284:183–185.

    Article  CAS  Google Scholar 

  • Efstratiadis, A., Kafatos, F. C., and Maniatis, T., 1977, The primary sequence of rabbit β-globin mRNA as determined from cloned DNA, Cell 10:571–585.

    Article  PubMed  CAS  Google Scholar 

  • Embury, S. H., Lebo, R. V., Dozy, A. M., and Kan, Y. W., 1979, Organization of the α-globin genes in the Chinese α-thalassemia syndromes, J. Clin. Invest. 63:1307–1310.

    Article  PubMed  CAS  Google Scholar 

  • Embury, S. H., Miller, J. A., Dozy, A. M., Kan, Y. W., Chan, V., and Todd, D., 1980, Two different molecular organizations account for the single α-globin gene of the α-thalassemia-2-genotype, J. Clin. Invest. 66:1319–1325.

    Article  PubMed  CAS  Google Scholar 

  • Engel, J. D., and Dodgson, J. B., 1980, Analysis of the closely linked adult chicken α-globin genes in recombinant DNAs, Proc. Natl. Acad. Sci. USA 77:2596–2600.

    Article  PubMed  CAS  Google Scholar 

  • Feldenzer, J., Mears, G., Burns, A. L., Natta, C., and Bank, C., 1979, Heterogeneity of DNA fragments associated with the sickle-globin gene, J. Clin. Invest. 64:751–755.

    Article  PubMed  CAS  Google Scholar 

  • Flavell, R. A., Kooter, J. M., DeBoer, E., Little, P. F. R., and Williamson, R., 1978, Analysis of the human β-δ-globin gene loci in normal and Hb Lepore DNA: Direct determination of gene linkage and intergene distance, Cell 15:25–41.

    Article  PubMed  CAS  Google Scholar 

  • Flavell, R. A., Bernards, R., Kooter, J. M., DeBoer, E., Little, P. F. R., Annison, G., and Williamson, R., 1979, The structure of the human β-globin gene in β-thalassemia, Nucleic Acids Res. 6:2749–2760.

    Article  PubMed  CAS  Google Scholar 

  • Forget, B. G., Hillman, D. G., Lazarus, H., Borell, E. F., Benz, E. J., Jr., Caskey, C. T., Huisman, T. H. J., Schroeder, W. A., and Housman, D., 1976, Absence of messenger RNA and gene DNA for beta globin chains in hereditary persistence of fetal hemoglobin, Cell 7:323–329.

    Article  PubMed  CAS  Google Scholar 

  • Forget, B. G., Wilson, J. T., Wilson, L. B., Cavallesco, C., Reddy, V. B., deRiel, J. K., Biro, P. A., Ghosh, P. K., and Weissman, S. M., 1980, Globin mRNA structure: General features and sequence homology, in: Cellular and Molecular Regulation of Hemoglobin Switching (G. Stamatoyannopoulos and A. W. Nienhuis, eds), pp. 569–593, Grune and Stratton, New York.

    Google Scholar 

  • Fritsch, E. F., Lawn, R. M., and Maniatis, T., 1979, Characterisation of deletions which affect the expression of fetal globin genes in man, Nature (London) 279:598–603.

    Article  CAS  Google Scholar 

  • Fritsch, E. F., Lawn, R. M., and Maniatis, T., 1980, Molecular cloning and characterization of the human β-like globin gene cluster, Cell 19:959–972.

    Article  PubMed  CAS  Google Scholar 

  • Gilbert, W., 1978, Why genes in pieces? Nature (London) 271:501–502.

    Article  CAS  Google Scholar 

  • Ginder, G. D., Wood, W. I., and Felsenfeld, G., 1979, Isolation and characterization of recombinant clones containing the chicken adult β-globin gene, J. Biol. Chem. 254:8099–8102.

    PubMed  CAS  Google Scholar 

  • Goossens, M., Dozy, A. M., Embury, S. H., Zachariades, Z., Hadjiminas, M. G., Stamatoyannopoulos, G., and Kan, Y. W., 1980, Triplicated α-globin loci in humans, Proc. Natl. Acad. Sci. USA 77:518–521.

    Article  PubMed  CAS  Google Scholar 

  • Gough, N. M., Kemp, D. J., Tyler, B. M., Adams, J. M., and Cory, S., 1980, Intervening sequences divide the gene for the constant region of mouse immunoglobulin μ chains into segments, each encoding a domain, Proc. Natl. Acad. Sci. USA 77:554–558.

    Article  PubMed  CAS  Google Scholar 

  • Grosschedl, R., and Birnstiel, M. L., 1980, Identification of regulatory sequences in the prelude sequences of an H2A histone gene by the study of specific deletion mutants in vivo, Proc. Natl. Acad. Sci. USA 77:1432–1436.

    Article  PubMed  CAS  Google Scholar 

  • Gusella, J., Varsanyi-Breiner, A., Kao, F.-T., Jones, C., Puck, T. T., Keys, C., Orkin, S., and Housman, D., 1979, Precise localization of human β-globin gene complex on chromosome 11, Proc. Natl. Acad. Sci. USA 76:5239–5243.

    Article  PubMed  CAS  Google Scholar 

  • Hamer, D., and Leder, P., 1979a, Expression of the chromosomal mouse βmaj-globin gene cloned in SV40, Nature (London) 281:35–40.

    Article  CAS  Google Scholar 

  • Hamer, D., and Leder, P., 1979b, SV40 recombinants carrying a functional RNA splice junction and polyadenylation site from the chromosomal mouse βmaj-globin gene, Cell 17:737–747.

    Article  PubMed  CAS  Google Scholar 

  • Hamer, D., and Leder, P., 1979c, Splicing and the formation of stable RNA, Cell 18:1299–1302.

    Article  PubMed  CAS  Google Scholar 

  • Hamer, D. H., Smith, K. D., Boyer, S. H., and Leder, P., 1979, SV40 recombinants carrying rabbit β-globin gene coding sequences, Cell 17:725–735.

    Article  PubMed  CAS  Google Scholar 

  • Hardison, R. C., Butler, E. T., III, Lacy, E., Maniatis, T., Rosenthal, N., and Efstratiadis, A., 1979, The structure and transcription of four linked rabbit β-like globin genes, Cell 18:1285–1297.

    Article  PubMed  CAS  Google Scholar 

  • Higgs, D. R., Old, J. M., Pressley, L., Clegg, J. B., and Weatherall, D. J., 1980, A novel α-globin gene arrangement in man, Nature (London) 284:632–635.

    Article  CAS  Google Scholar 

  • Hollan, S. R., Szelenyi, J. G., Brimhall, B., Duerst, M., Jones, R. T., Koler, R. P., and Stocklenz, A., 1972, Multiple alpha chain loci for human haemoglobins: Hb J-Buda and Hb G-Pest, Nature (London) 235:47–50.

    Article  CAS  Google Scholar 

  • Housman, D., Forget, B. G., Skoultchi, A., and Benz, E. J., Jr., 1973, Quantitative deficiency of chain specific globin messenger ribonucleic acids in the thalassemia syndromes, Proc. Natl. Acad. Sci. USA 70:1809–1813.

    Article  PubMed  CAS  Google Scholar 

  • Huisman, T. H. J., Schroeder, W. A., Etremer, G. D., Dume, H., Miller, A., Brodie, A., Shelton, J. R., Shelton, J. B., and Apell, G., 1974, The present status of the heterogeneity of fetal hemoglobin in β-thalassemia: An attempt to unify some observations in thalassemia and related disorders, Ann. N.Y. Acad. Sci. 232:107–122.

    Article  PubMed  CAS  Google Scholar 

  • Hutchison, C. A., III, Phillips, S., Edgell, M. H., Gillam, S., Jahnke, P., and Smith, M., 1978, Mutagenesis at a specific position in a DNA sequence, J. Biol. Chem. 253:6551–6560.

    PubMed  CAS  Google Scholar 

  • Jeffreys, A. J., 1979, DNA sequence variants in the Gγ-, Aγ-, δ-, and β-globin genes in man, Cell 18:1–10.

    Article  PubMed  CAS  Google Scholar 

  • Jeffreys, A. J., and Flavell, R. A., 1977a, A physical map of the DNA regions flanking the rabbit β-globin gene, Cell 12:429–439.

    Article  PubMed  CAS  Google Scholar 

  • Jeffreys, A. J., and Flavell, R. A., 1977b, The rabbit β-globin gene contains a large insert in the coding sequence, Cell 12:1097–1108.

    Article  PubMed  CAS  Google Scholar 

  • Jelinek, W. R., Toomey, T. P., Leinwand, L., Duncan, C. H., Biro, P. A., Chondary, P. V., Weissman, S. M., Rubin, C. M., Houck, C. M., Deininger, P. L., and Schmid, C. W., 1980, Ubiquitous, interspersed repeated sequences in mammalian genomes, Proc. Natl. Acad. Sci. USA 77:1398–1402.

    Article  PubMed  CAS  Google Scholar 

  • Kacian, D. L., Gambino, R., Dow, L. W., Grossbard, E., Natta, C., Ramirez, F., Spiegelman, S., Marks, P. A., and Bank, A., 1973, Decreased globin messenger RNA in thalassemia detected by molecular hybridization, Proc. Natl. Acad. Sci. USA 70:1886–1890.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., and Dozy, A. M., 1978a, Polymorphism of DNA sequence adjacent to the human β-globin structural gene: Relationship to sickle mutation, Proc. Natl. Acad. Sci. USA 75:5631–5635.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., and Dozy, A. M., 1978b, Antenatal diagnosis of sickle cell anemia by DNA analysis of amniotic fluid cells, Lancet ii:91–93.

    Google Scholar 

  • Kan, Y. W., and Dozy, A. M., 1979, The evolution of the S and C genes in the world populations (Abstract), Clin. Res. 27:274A.

    Google Scholar 

  • Kan, Y. W., and Dozy, A. M., 1980, Evolution of the hemoglobin S and C genes in world populations, Science 209:388–390.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., Schwartz, E., and Nathan, D. G., 1968, Globin chain synthesis in the alpha thalassemia syndrome, J. Clin. Invest. 47:2515–2522.

    Article  CAS  Google Scholar 

  • Kan, Y. W., Forget, B. G., and Nathan, D. G., 1972, γβ-Thalassemia: A cause of hemolytic disease of newborns, N. Engl. J. Med. 286:129–134.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., Holland, J. P., Dozy, A. M., and Varmus, H. E., 1975a, Demonstration of nonfunctional β-globin mRNA in homozygous β°-thalassemia, Proc. Natl. Acad. Sci. USA 72:5140–5144.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., Dozy, A. M., Varmus, H. E., Taylor, J. M., Holland, J. P., Lie-Injo, L. E., Ganesan, J., and Todd, D., 1975b, Deletion of α-globin genes in haemoglobin-H disease demonstrates multiple α-globin structural loci, Nature (London) 255:255–256.

    Article  CAS  Google Scholar 

  • Kan, Y. W., Holland, J. P., Dozy, A. M., Charache, S., and Kazazian, H. H., Jr., 1975c, Deletion of the β-globin structural gene in hereditary persistence of foetal haemoglobin, Nature (London) 258:162–163.

    Article  CAS  Google Scholar 

  • Kan, Y. W., Dozy, A. M., Trecartin, R., and Todd, D., 1977, Identification of a nondeletion defect in α-thalassemia, N. Engl. J. Med. 297:1081–1084.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., Dozy, A. M., Stamatoyannopoulos, G., Hadjiminas, M. G., Zacharaides, Z., Furbetta, M., and Cao, A., 1979, Molecular basis of hemoglobin-H disease in the Mediterranean population, Blood 54:1434–1438.

    PubMed  CAS  Google Scholar 

  • Kan, Y. W., Lee, K. Y., Furbetta, M., Angius, A., and Cao, A., 1980a, Polymorphism of DNA sequence in the β-globin gene region: Application to prenatal diagnosis of β0- thalassemia in Sardinia, N. Engl. J. Med. 302:185–188.

    Article  PubMed  CAS  Google Scholar 

  • Kan, Y. W., Chang, J. C., and Poon, R., 1980b, Nucleotide sequences of the untranslated 5′ and 3′ regions of human α, β, and γ-globin mRNAs, in: Cellular and Molecular Regulation of Hemoglobin Switching (G. Stamatoyannopoulos, and A. W. Nienhuis, eds.), pp. 595–606, Grune and Stratton, New York.

    Google Scholar 

  • Kantor, J. A., Turner, P. H., and Nienhuis, A. W., 1980, Beta thalassemia: Mutations which affect processing of the β-globin in RNA precursor, Cell 21:149–157.

    Article  PubMed  CAS  Google Scholar 

  • Kinniburgh, A. J., and Ross, J., 1979, Processing of the mouse β-globulin mRNA precursor: At least two cleavage-ligation reactions are necessary to excise the larger intervening sequence, Cell 17:915–921.

    Article  PubMed  CAS  Google Scholar 

  • Kinniburgh, A. J., Mertz, J. E., and Ross, J., 1978, The precursor of mouse β-globin messenger RNA containing two intervening RNA sequences, Cell 14:681–693.

    Article  PubMed  CAS  Google Scholar 

  • Konkel, D. A., Tilghman, S. M., and Leder, P., 1978, The sequence of the chromosomal mouse β-globin major gene: Homologies in capping, splicing, and poly (A) sites, Cell 15:1125–1132.

    Article  PubMed  CAS  Google Scholar 

  • Konkel, D. A., Maizel, J. V., Jr., and Leder, P., 1979, The evolution and sequence comparison of two recently diverged mouse chromosomal β globin genes, Cell 18:865–873.

    Article  PubMed  CAS  Google Scholar 

  • Lacy, E., Hardison, R. C., Quon, D., and Maniatis, T., 1979, The linkage arrangement of four rabbit β-like globin genes, Cell 18:1273–1283.

    Article  PubMed  CAS  Google Scholar 

  • Lai, E. C., Stein, J. P., Catterall, J. F., Woo, S. L., Mace, M. L., Means, A. R., and O’Malley, B. W., 1979, Molecular structure and flanking nucleotide sequences of the natural chicken ovomucoid gene, Cell 18:629–642.

    Article  Google Scholar 

  • Lauer, J., Shen, C.-K. J., and Maniatis, T., 1980, The chromosomal arrangement of human α-like globin genes: Sequence homology and α-globin gene deletions, Cell 20:119–130.

    Article  PubMed  CAS  Google Scholar 

  • Lawn, R. M., Fritsch, E. F., Parker, R. C., Blake, G., and Maniatis, T., 1978, The isolation and characterization of linked δ- and β-globin genes from a cloned library of human DNA, Cell 15:1157–1174.

    Article  PubMed  CAS  Google Scholar 

  • Lebo, R. V., Carrans, A. V., Burkhart-Schultz, K., Dozy, A. M., Yu, L.-C., and Kan, Y. W., 1979, Assignment of human β-, γ-, and δ-globin genes to the short arm of chromosome 11 by chromosome sorting and DNA restriction enzyme analysis, Proc. Natl. Acad. Sci. USA 76:5804–5808.

    Article  PubMed  CAS  Google Scholar 

  • Leder, A., Miller, H. I., Hamer, D. H., Seidman, J. G., Norman, B., Sullivan, M., and Leder, P., 1978, Comparison of cloned mouse α- and β-globin genes: Conservation of intervening sequence locations and extragenic homology, Proc. Natl. Acad. Sci. USA 75:6187–6191.

    Article  PubMed  CAS  Google Scholar 

  • Leder, P., 1978, Discontinuous genes, N. Engl. J. Med. 298:1079–1081.

    Article  PubMed  CAS  Google Scholar 

  • Leder, P., Tiemeier, D., and Enquist, L., 1977, EK2 derivatives of bacteriophage lambda useful in the cloning of DNA from higher organisms: The XgtWES system, Science 196:175–177.

    Article  PubMed  CAS  Google Scholar 

  • Lehmann, H., 1970, Different types of alpha thalassaemia and significance of haemoglobin Bart’s in neonates, Lancet ii:78–80.

    Article  Google Scholar 

  • Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L., and Steitz, J. A., 1980. Are snRNPs involved in splicing?, Nature (London) 283:220–224.

    Article  CAS  Google Scholar 

  • Little, P. F. R., Curtis, P., Contelle, C., van den Berg, J., Dalgleish, R., Malcolm, S., Courtney, M., Westaway, D., and Williamson, R., 1978, Isolation and partial sequence of recombinant plasmids containing human α-, β-, and γ-globin cDNA proponents, Nature (London) 273:640–643.

    Article  CAS  Google Scholar 

  • Little, P. F. R., Flavell, R. A., Kooter, J. M., Annison, G., and Williamson, R., 1979, Structure of the human fetal globin gene locus, Nature (London) 278:227–231.

    Article  CAS  Google Scholar 

  • Little, P. F. R., Annison, G., Darling, S., Cleamson, R. W., Camba, L., and Modell, B., 1980a, Model for antenatal diagnosis of β-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphisms, Nature (London) 285:144–147.

    Article  CAS  Google Scholar 

  • Little, P. F. R., Whitelaw, E., Annison, G., Williamson, R., Kooter, J. M., Flavell, R. A., Goossens, M., Sergeant, G. R., and Montgomery, D., 1980b, The detection and use of hemoglobin mutants in the direct analysis of human globin genes, Blood 55:1060–1062.

    PubMed  CAS  Google Scholar 

  • Lomedico, P., Rosenthal, N., Efstratiadis, A., Gilbert, W., Kolodner, R., and Tizard, R., 1979, The structure and evolution of two nonallelic rat preproinsulin genes, Cell 18:545–558.

    Article  PubMed  CAS  Google Scholar 

  • Maniatis, T., Kee, S. K., Efstratiadis, A., and Kafatos, F. C., 1976, Amplification and characterization of a β-globin gene synthesized in vitro, Cell 8:163–182.

    Article  PubMed  CAS  Google Scholar 

  • Maniatis, T., Hardison, R. C., Lacy, E., Lauer, J., O’Connell, C., Quon, D., Sim, G. K., and Efstratiadis, A., 1978, The isolation of structural genes from libraries of eucaryotic DNA, Cell 15:687–701.

    Article  PubMed  CAS  Google Scholar 

  • Manley, J. L., Five, A., Cano, A., Sharp, P. A., and Gefter, M. L., 1980, DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract, Proc. Natl. Acad. Sci. USA 77:3855–3859.

    Article  PubMed  CAS  Google Scholar 

  • Mantei, N., Boll, W., and Weissmann, C., 1979, Rabbit β-globin mRNA production in mouse L cells transformed with cloned rabbit β-globin chromosomal DNA, Nature (London) 281:40–46.

    Article  CAS  Google Scholar 

  • Maquat, L. E., Kinniburgh, A. J., Beach, L. R., Honig, G. R., Lazerson, J., Ershler, W. B., and Roos, J., 1980, Processing of the human β-globin mRNA precursor to mRNA is defective in three β +-thalassemias, Proc. Natl. Acad. Sci. USA 77:4287–4291.

    Article  PubMed  CAS  Google Scholar 

  • Marotta, C. A., Wilson, J. T., Forget, B. G., and Weissman, S. M., 1977, Human β-globin messenger RNA. III. Nucleotide sequences derived from complementary DNA, J. Biol. Chem. 252:5040–5053.

    PubMed  CAS  Google Scholar 

  • Maxam, A. M., and Gilbert, W., 1977, A new method for sequencing DNA, Proc. Natl. Acad. Sci. USA 74:560–564.

    Article  PubMed  CAS  Google Scholar 

  • Mears, J. G., Ramirez, F., Leibowitz, D., Nakamura, F., Bloom, A., Konotey-Abulu, F., and Bank, A., 1978a, Changes in restricted human cellular DNA fragments containing globin gene sequences in thalassemias and related disorders, Proc. Natl. Acad. Sci. USA 75:1222–1226.

    Article  CAS  Google Scholar 

  • Mears, J. G., Ramirez, F., Leibowitz, D., and Bank, A., 1978b, Organization of human δ-and β-globin genes in cellular DNA and the presence of intragenic inserts, Cell 15:15–23.

    Article  PubMed  CAS  Google Scholar 

  • Meloni, T., Pilo, G., Camardella, L., Cancedda, F., Lania, A., Pepe, G., and Luzzatto, L., 1980, Coexistence of three hemoglobins with different α-chains in two unrelated children (with family studies indicating polymorphism in the number of α-globin genes in the Sardinian population), Blood 55:1025–1032.

    PubMed  CAS  Google Scholar 

  • Michelson, A., and Orkin, S. H., 1980, The 3’-untranslated regions of the duplicated human α-globin genes are unexpectedly divergent, Cell 22:371–377.

    Article  PubMed  CAS  Google Scholar 

  • Mulligan, R. C., Howard, B. H., and Berg, P., 1979, Synthesis of rabbit β-globin in cultured monkey kidney cells following infection with a SV40 β-globin recombinant genome, Nature (London) 277:108–114.

    Article  CAS  Google Scholar 

  • Nathan, D. G., Alter, B. P., and Orkin, S. H., 1979, Prenatal diagnosis of hemoglobinopathies, Clin. Perinatol. 6:275–291.

    PubMed  CAS  Google Scholar 

  • Nathans, D., 1979, Restriction endonucleases, simian virus 40, and the new genetics, Science 206:903–909.

    Article  PubMed  CAS  Google Scholar 

  • Nienhuis, A. W., Turner, P., and Benz, E. J., Jr., 1977, Relative stability of α- and β-globin messenger RNAs in homozygous β-thalassemia, Proc. Natl. Acad. Sci. USA 74:3960–3964.

    Article  PubMed  CAS  Google Scholar 

  • Nishioka, Y., and Leder, P., 1979, The complete sequence of a chromosomal mouse α-globin gene reveals elements conserved throughout vertebrate evolution, Cell 18:875–882.

    Article  PubMed  CAS  Google Scholar 

  • Nishioka, Y., Leder, A., and Leder, P., 1980, Unusual α-globin-like gene that has clearly lost both globin intervening sequences, Proc. Natl. Acad. Sci. USA 77:2806–2809.

    Article  PubMed  CAS  Google Scholar 

  • Old, J., Longley, J., Wood, W. G., Clegg, J. B., and Weatherall, D. J., 1977, Molecular basis for acquired haemoglobin H disease, Nature (London) 269:524–525.

    Article  CAS  Google Scholar 

  • Old, J. M., Clegg, J. B., Weatherall, D. J., and Booth, P. B., 1978a, Haemoglobin J. Tongariki is associated with α-thalassaemia, Nature (London) 273:319–320.

    Article  CAS  Google Scholar 

  • Old, J. M., Proudfoot, N. J., Wood, W. G., Longley, J. I., Clegg, J. B., and Weatherall, D. J., 1978b, Characterization of β-globin mRNA in the β°-thalassemias, Cell 14:289–298.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., 1978, The duplicated human α-globin genes lie close together in cellular DNA, Proc. Natl. Acad. Sci. USA 75:5950–5954.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., and Michelson, A., 1980, Partial deletion of the α-globin structural gene in human α-thalassaemia, Nature (London) 286:538–540.

    Article  CAS  Google Scholar 

  • Orkin, S. H., and Nathan, D. G., 1976, The thalassemias, N. Engl. J. Med. 295:710–714.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., Alter, B. P., Altay, C., Mahoney, M. J., Lazarus, H., Hobbins, J. C., and Nathan, D. G., 1978, Application of restriction endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin gene deletion, N. Engl. J. Med. 289:166–172.

    Article  Google Scholar 

  • Orkin, S. H., Old, J., Lazarus, H., Altay, C., Gurgey, A., Weatherall, D. J., and Nathan, D. G., 1979a, The molecular basis of α-thalassemias: Frequent occurrence of dysfunctional a loci among non-Asians with Hb H disease, Cell 17:33–42.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., Old, J. M., Weatherall, D. J., and Nathan, D. G., 1979b, Partial deletion of β-globin gene DNA in certain patients with β°-thalassemia, Proc. Natl. Acad. Sci. USA 76:2400–2404.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., Alter, B. P., and Altay, C., 1979c, Deletion of the Aγ globin gene in Cγ-δβ-thalassemia, J. Clin. Invest. 64:866–869.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., Kolodner, R., Michelson, A., and Husson, R., 1980a, Cloning and direct examination of a structurally abnormal human β°-thalassemia globin gene, Proc. Natl. Acad. Sci. USA 77:3558–3562.

    Article  PubMed  CAS  Google Scholar 

  • Orkin, S. H., Goff, S., and Nathan, D. G., 1980b, Molecular heterogeneity in the deletion in γδβ-thalassemia, J. Clin. Invest. (in press).

    Google Scholar 

  • Ottolenghi, S., Lanyon, W. G., Paul, J., Williamson, R., Weatherall, D. J., Clegg, J. B., Pritchard, J., Pootrakul, S., and Boon, W. H., 1974, The severe form of α-thalassaemia is caused by a haemoglobin gene deletion, Nature (London) 251:389–392.

    Article  CAS  Google Scholar 

  • Ottolenghi, S., Comi, P., Giglioni, B., Tolstoshev, P., Lanyon, W. G., Mitchell, G. J., Williamson, R., Russo, G., Musumeci, S., Schiliro, G., Tsistrakis, G. A., Charache, S., Wood, W. G., Clegg, J. B., and Weatherall, D. J., 1976, δβ-Thalassemia is due to a gene deletion, Cell 9:71–80.

    Article  PubMed  CAS  Google Scholar 

  • Ottolenghi, S., Giglioini, B., Comi, P., Gianni, A. M., Polli, E., Acquaye, C. T. A., Oldham, J. H., and Masera, G., 1979, Globin gene deletion in HPFH, δ°β°-thalassemia and Hb Lepore disease, Nature (London) 278:654–657.

    Article  CAS  Google Scholar 

  • Phillips, J. A., III, Scott, A. F., Smith, K. D., Young, K. E., Lightbody, K. L., Jiji, R. M., and Kazazian, H. H., Jr., 1979, A molecular basis for hemoglobin H disease in American Blacks, Blood 54:1439–1445.

    PubMed  Google Scholar 

  • Phillips, J. A., III, Panny, S. R., Kazazian, H. H., Jr., Boehm, C., Scott, A. F., And Smith, D. D., 1980a, Prenatal diagnosis of sickle cell anemia by restriction endonuclease analysis: Hind III polymorphism in γ-globin genes extend test applicability, Proc. Natl. Acad. Sci. USA 77:2853–2856.

    Article  PubMed  CAS  Google Scholar 

  • Phillips, J. A., III, Vik, T. A., Scott, A. F., Young, K. E., Kazazian, H. H., Jr., Smith, K. D., Fairbanks, V. F., and Koenig, H. M., 1980b, Unequal crossing-over: A common basis of single α-globin genes in Asians and American Blacks with hemoglobin H disease, Blood 55:1066–1069.

    PubMed  CAS  Google Scholar 

  • Pressley, L., Higgs, D. R., Clegg, J. B., and Weatherall, D. J., 1980, Gene deletions in α-thalassemia prove that 5’ ζ locus is functional, Proc. Natl. Acad. Sci. USA 77:3586–3589.

    Article  PubMed  CAS  Google Scholar 

  • Proudfoot, N. J., Gillam, S., Smith, M., and Longley, J. I., 1977, Nucleotide sequence of the 3′-terminal third of rabbit α-globin messenger RNA: Comparison with human α-globin messenger RNA, Cell 11:807–818.

    Article  PubMed  CAS  Google Scholar 

  • Ramirez, F., O’Donnell, J. V., Marks, P. A., Bank, A., Musumeci, S., Schiliro, G., Pizzarelli, G., Russo, G., Luppis, R., and Gambino, R., 1976, Abnormal or absent β-mRNA in β°-Ferrara and gene deletion in δβ-thalassemia, Nature (London) 263:471–475.

    Article  CAS  Google Scholar 

  • Roberts, R., 1980, Directory of restriction endonucleases, in: Methods in Enzymology, Vol. 65 (L. Grossman and K. Moldane, eds.), pp. 1–15, Academic Press, New York.

    Google Scholar 

  • Rogers, J., and Wall, R., 1980, A mechanism for RNA splicing, Proc. Natl. Acad. Sci. USA 77:1877–1879.

    Article  PubMed  CAS  Google Scholar 

  • Ross, J., 1976, A precursor of globin messenger RNA, J. Mol. Biol. 106:402–420.

    Article  Google Scholar 

  • Ross, J., and Knecht, D. A., 1978, Precursors of alpha and beta globin messenger RNAs, J. Mol. Biol. 119:1–20.

    Article  PubMed  CAS  Google Scholar 

  • Rutherford, T. R., Clegg, J. B., and Weatherall, D. J., 1979, K562 human leukemic cells synthesise embryonic haemoglobin in response to haemin, Nature (London) 280:164–165.

    Article  CAS  Google Scholar 

  • Sakano, H., Rogers, J. H., Huppi, K., Brack, C., Traunecher, A., Maki, R., Wall, R., and Tonegawa, S., 1979, Domains and the hinge region of an immunoglobulin heavy chain are encoded in separate DNA segments, Nature (London) 277:627–633.

    Article  CAS  Google Scholar 

  • Sanders-Haigh, L., Anderson, W. F., and Franche, U., 1980, The β-globin gene is on the short arm of human chromosome 11, Nature (London) 283:683–686.

    Article  CAS  Google Scholar 

  • Sanger, F., and Coulson, A. R., 1975, A rapid method for determining sequences in DNA by primer synthesis with DNA polymerase, J. Mol. Biol. 94:441–448.

    Article  PubMed  CAS  Google Scholar 

  • Scott, A. F., Phillips, J. A., III, and Migeon, B. R., 1979, DNA restriction endonuclease analysis for localization of human β- and δ-globin genes on chromosome 11, Proc. Natl. Acad. Sci. USA 76:4563–4565

    Article  PubMed  CAS  Google Scholar 

  • Seidman, J. G., Leder, A., Nau, M., Norman, B., and Leder, P., 1978, Antibody diversity, Science 202:11–17.

    Article  PubMed  CAS  Google Scholar 

  • Senno, L. D., Conconi, F., Little, P. F. R., and Williamson, R., 1979, Restriction enzyme analysis of the β-globin gene in DNA from β°-thalassemic subjects from Ferrara, Biophys. Biochem. Res. Commun. 91:548–553.

    Article  Google Scholar 

  • Shen, C.-K. J., and Maniatis, T., 1980, The organization of repetitive sequences in a cluster of rabbit β-like globin genes, Cell 19:379–391.

    Article  PubMed  CAS  Google Scholar 

  • Shortie, D., and Nathans, D., 1978, Local mutagenesis: A method for generating viral mutants with base substitutions in preselected regions of the viral genome, Proc. Natl. Acad. Sci. USA 75:2170–2174.

    Article  Google Scholar 

  • Smithies, O., Blechl, A. E., Denniston-Thompson, K., Newell, N., Richards, J. E., Slighton, J. L., Tucker, P. W., and Blattner, F. R., 1978, Cloning human foetal γ-globin and mouse α-type globin DNA: Characterization and partial sequencing, Science 202:1284–1289.

    Article  PubMed  CAS  Google Scholar 

  • Southern, E. M., 1975, Detection of specific sequences among DNA fragments by gel electrophoresis, J. Mol. Biol. 98:503–577.

    Article  PubMed  CAS  Google Scholar 

  • Sternberg, N., Tiemeier, D., and Enquist, L., 1977, In vitro packaging of a λ-Dam vector containing Eco RI DNA fragments of E. coli and phage P1, Gene 1:255–280.

    Article  PubMed  CAS  Google Scholar 

  • Surrey, S., Chambers, J. S., Muni, D., and Schwartz, E., 1978, Restriction endonuclease analysis of human globin genes in cellular DNA, Biochem. Biophys. Res. Commun. 83:1125–1131.

    Article  PubMed  CAS  Google Scholar 

  • Swanstrom, R., and Shank, P. R., 1978, X-ray intensifying screens greatly enhance the detection by autoradiography of the radioactive isotopes 32P and 125I, Anal. Biochem. 86:184–192.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, J. M., Dozy, A., Kan, Y. W., Varmus, H. G., Lie-Injo, L. E., Ganesan, J., and Todd, D., 1974, Genetic lesion in homozygous α-thalassaemia (hydrops fetalis), Nature (London) 251:392–393.

    Article  CAS  Google Scholar 

  • Temple, G. F., Chang, J. C., and Kan, Y. W., 1977, Authentic β-globin mRNA sequences in homozygous β°-thalassemia, Proc. Natl. Acad. Sci. USA 74:3047–3051.

    Article  PubMed  CAS  Google Scholar 

  • Tiemeier, D. C., Tilghman, S. M., Polsky, F. I., Seidman, J. G., Leder, A., Edgell, M. H., and Leder, P., 1978, A comparison of two cloned mouse β-globin genes and their surrounding and intervening sequences, Cell 14:237–245.

    Article  PubMed  CAS  Google Scholar 

  • Tilghman, S. M., Tiemeier, D. C., Polsky, F., Edgell, M. H., Seiiman, J. G., Leder, A., Enquist, L. W., Norman, B., and Leder, P., 1977, Cloning specific segments of the mammalian genome: Bacteriophage X containing mouse globin and surrounding gene sequences, Proc. Natl. Acad. Sci. USA 74:4406–4410.

    Article  PubMed  CAS  Google Scholar 

  • Tilghman, S. M., Tiemeier, D. C., Seidman, J. G., Peterlin, B. M., Sullivan, M., Maizel, J. V., and Leder, P., 1978a, Intervening sequences of DNA identified in the structural portion of a mouse β-globin gene, Proc. Natl. Acad. Sci. USA 75:725–729.

    Article  PubMed  CAS  Google Scholar 

  • Tilghman, S. M., Curtis, P. J., Tiemeier, D. C., Leder, P., and Weissmann, C., 1978b, The intervening sequence of a mouse β-globin gene is transcribed within the 15S β-globin mRNA precursor, Proc. Natl. Acad. Sci. USA 75:1309–1313.

    Article  PubMed  CAS  Google Scholar 

  • Tolstoshev, P., Mitchell, J., Lanyon, G., Williamson, R., Ottolenghi, S., Comi, S., Giglioni, B., Masera, G., Modell, B., Weatherall, D., and Clegg, J. B., 1976, Presence of gene for β-globin in homozygous β°-thalassaemia, Nature (London) 259:95–98.

    Article  CAS  Google Scholar 

  • Tuan, D., Biro, P. A., deRiel, J. K., Lazarus, H., and Forget, B. G., 1979, Restriction endonuclease mapping of the human γ-globin gene loci, Nucleic Acids Res. 6:2519–2544.

    Article  PubMed  CAS  Google Scholar 

  • Tuan, D., Murnane, M. J., deRiel, J. K., and Forget, B. G., 1980, Heterogeneity in the molecular bases of hereditary persistence of fetal haemoglobin, Nature (London) 285:335–337.

    Article  CAS  Google Scholar 

  • Van den Berg, J., van Ooyen, J., Mantei, A., Schambock, N., Grosveld, A., Flavell, R. A., and Weissmann, C., 1978, Comparison of cloned rabbit and mouse β-globin genes showing strong evolutionary divergence of two homologous pairs of introns, Nature (London) 276:37–44.

    Article  Google Scholar 

  • Van der Ploeg, L. H. T., and Flavell, R. A., 1980a, DNA methylation in the human γδβ-globin locus in erythroid and nonerythroid tissues, Cell 19:947–958.

    Article  PubMed  Google Scholar 

  • Van der Ploeg, L. H. T., Konings, A., Oort, M., Roos, D., Bernini, L., and Flavell, R. A., 1980b, γ-β-Thalassaemia studies showing that deletion of the γ- and δ-genes influences β-globin gene expression in man, Nature (London) 283:637–642.

    Article  Google Scholar 

  • Van Ooyen, A., van den Berg, J., Mantei, N., and Weissmann, C., 1979, Comparison of total sequence of a cloned rabbit β-globin gene and its flanking regions with a homologous mouse sequence, Science 206:337–344.

    Article  PubMed  Google Scholar 

  • Wahli, W., David, I. B., Wyler, T., Weber, R., and Ryffel, G. U., 1980, Comparative analysis of the structural organization of two closely related vitellogenin genes in X. laevis, Cell 20:107–117.

    Article  PubMed  CAS  Google Scholar 

  • Wald, B., Wigen, M., Lacy, E., Maniatis, T., Silverstein, S., and Arnel, R., 1979, Introduction and expression of a rabbit β-globin gene in mouse fibroblasts, Proc. Natl. Acad. Sci. USA 76:5634–5688.

    Google Scholar 

  • Wasylyk, B., Kedinger, C., Corden, J., Brison, O., and Chambon, P., 1980, Specific in vitro initiation of transcription on conalbumin and ovalbumin genes and comparison with adenovirus-2 early and late genes, Nature (London) 285:367–373.

    Article  CAS  Google Scholar 

  • Weatherall, D. J., and Clegg, J. B., 1972, The Thalassaemia Syndromes, 2nd edn, Blackwell, Oxford.

    Google Scholar 

  • Weatherall, D. J., and Clegg, J. B., 1979, Recent developments in the molecular genetics of human haemoglobin, Cell 16:467–479.

    Article  PubMed  CAS  Google Scholar 

  • Weil, P. A., Luse, D. S., Segall, J., and Roeder, R. G., 1979, Selective and accurate initiation of transcription at the Ad2 major late promoter in a soluble system dependent on purified RNA polymerase II and DNA, Cell 18:469–484.

    Article  PubMed  CAS  Google Scholar 

  • Weintraub, H., and Groudine, M., 1976, Chromosomal subunits in active genes have an altered conformation, Science 93:848–853.

    Article  Google Scholar 

  • Wigler, M., Sweet, R., Sim, G. K., Wold, B., Pellicer, A., Lacy, E., Maniatis, T., Silverstein, S., and Axel, R., 1979, Transformation of mammalian cells with genes from procaryotes and eucaryotes, Cell 16:777–785.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. T., deRiel, J. K., Forget, B. G., Marotta, C. A., and Weissman, S. M., 1977, Nucleotide sequence of the 3′-untranslated portion of human alpha globin mRNA, Nucleic Acids Res. 4:2353–2368.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. T., Wilson, L. B., deRiel, J. K., Villa-Komaroff, L., Efstratiadis, A., Forget, B. G., and Weissman, S. M., 1978, Insertion of synthetic copies of human globin genes into bacterial plasmids, Nucleic Acids Res. 5:563–581.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. T., Wilson, L. B., Reddy, V. B., Cavallesco, C., Ghosh, P. K., deRiel, J. K., Forget, B. G., and Weissman, S. M., 1980, Nucleotide sequence of the coding portion of human α-globin messenger RNA, J. Biol. Chem. 255:2807–2815.

    PubMed  CAS  Google Scholar 

  • Wood, W. G., Clegg, J. B., and Weatherall, D. J., 1979, Hereditary persistence of fetal haemoglobin (HPFH) and δβ-thalassaemia, Br. J. Haematol. 43:509–520.

    Article  PubMed  CAS  Google Scholar 

  • Young, N. S., Benz, E. J., Jr., and Nienhuis, A. W., 1980, Structure of the individual globin genes in chromatin, in: Cellular and Molecular Regulation of Hemoglobin Switching (G. Stamatoyannopoulos, and A. W. Nienhuis, eds.), pp. 749–760, Grune and Stratton, New York.

    Google Scholar 

  • Zimmer, E. A., Martin, S. L., Beverley, S. M., Kan, Y. W., and Wilson, A. C., 1980, Rapid duplication and loss of genes coding for the alpha chains of hemoglobin, Proc. Natl. Acad. Sci. USA 77:2158–2162.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, The Children’s Hospital Medical Center, Boston, Massachusetts, 02115, USA

    Stuart H. Orkin & David G. Nathan

  2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Stuart H. Orkin & David G. Nathan

Authors
  1. Stuart H. Orkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David G. Nathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Pennsylvania, Philadelphia, USA

    Harry Harris (Harnwell Professor Human Genetics) (Harnwell Professor Human Genetics)

  2. Mount Sinai School of Medicine, The City University of New York, USA

    Kurt Hirschhorn (Herbert H. Lehman Professor and Chairman of Pediatrics) (Herbert H. Lehman Professor and Chairman of Pediatrics)

Rights and permissions

Reprints and permissions

Copyright information

© 1981 Plenum Press, New York

About this chapter

Cite this chapter

Orkin, S.H., Nathan, D.G. (1981). The Molecular Genetics of Thalassemia. In: Harris, H., Hirschhorn, K. (eds) Advances in Human Genetics 11. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8303-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-8303-5_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-8305-9

  • Online ISBN: 978-1-4615-8303-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation