Advertisement

Antenatal Diagnosis of Hemoglobinopathies

  • John M. Old
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 91)

Abstract

The hemoglobinopathies are a diverse group of inherited recessive disorders that include the thalassemias and sickle-cell disease. They were the first genetic diseases to be characterized at the molecular level and consequently have been used as a prototype for the development of new techniques of mutation detection. There are now many different polymerase chain reaction (PCR)-based techniques that can be used to diagnose the globin gene mutations, including dot blot analysis, reverse dot blot analysis, the amplification refractory mutation system (ARMS), denaturing gradient gel electrophoresis (DGGE), mutagenically separated PCR, gap-PCR, and restriction endonuclease (RE) analysis (1,2). Each method has its advantages and disadvantages, and the particular one chosen by a laboratory to diagnose point mutations depends not only on the technical expertise available in the diagnostic laboratory but also on the type and variety of the mutations likely to be encountered in the individuals being screened.

Keywords

Prenatal Diagnosis Preimplantation Genetic Diagnosis Globin Gene Variable Number Tandem Repeat Amplification Refractory Mutation System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Embury, S. H. (1995) Advances in the prenatal and molecular diagnosis of the haemoglobinopathies and thalassaemias. Hemoglobin 19, 237–261PubMedCrossRefGoogle Scholar
  2. 2.
    Old, J. (1996) Haemoglobinopathies. Prenat. Diag. 16, 1181–1186.CrossRefGoogle Scholar
  3. 3.
    Old, J. M., Ward, R. H. T., Petrou, M., Karagozulu, F., Modell, B., and Weatherall, D. J. (1982) First-trimester fetal diagnosis for haemoglobinopathies: three cases. Lancet ii, 1413–1416.CrossRefGoogle Scholar
  4. 4.
    Working Party of the General Haematology Task Force of the British Committee for Standards in Haematology. (1998) Guideline. The Laboratory Diagnosis of Haemoglobinopathies. Br. J. Haematol. 101, 783–792.CrossRefGoogle Scholar
  5. 5.
    Thein, S. L., Eshari, A., and Wallace, R. B. (1993) The use of synthetic oligonucleotides as specific hybridisation probes in the diagnosis of genetic disorders, in Human Genetic Disease Analysis: A Practical Approach (Davies, K. E., ed.), IRL Press, Oxford, pp. 22–33.Google Scholar
  6. 6.
    Bowden, D. K., Vickers, M. A., and Higgs, D. R. (1992) A PCR-based strategy to detect the common severe determinants of a-thalassaemia. Br. J. Haematol. 81, 104–108.PubMedCrossRefGoogle Scholar
  7. 7.
    Baysal, E. and Huisman, T. H. J. (1994) Detection of common deletional α-thalassaemia-2 determinants by PCR. Am. J. Hematol. 46, 208.PubMedCrossRefGoogle Scholar
  8. 8.
    Liu, Y. T., Old, J. M., Fisher, C. A., Weatherall, D. J., and Clegg, J. B. (1999) Rapid detection of α-thalassaemia deletions and α-globin gene triplication by multiplex polymerase chain reactions. Br. J. Haematol. 108, 295–299.CrossRefGoogle Scholar
  9. 9.
    Chong, S. S., Boehm, C. D., Higgs, D. R., and Cutting, G. R. (2000) Single-tube multiplex-PCR screen for common deletional determinants of α-thalassemia. Blood 95, 360–362.PubMedGoogle Scholar
  10. 10.
    Old, J. M. (1996) Haemoglobinopathies. Community clues to mutation detection, in Methods in Molecular Medicine: Molecular Diagnosis of Genetic Diseases (Elles, R., ed.), Humana Press Inc., Totowa, NJ, pp. 169–183.CrossRefGoogle Scholar
  11. 11.
    Hartveld, K. L., Heister, A. J. G. A. M., Giordano, P. C, Losekoot, M., and Bernini, L. F. (1996) Rapid detection of point mutations and polymorphisms of the α-globin genes by DGGE and SSCA. Hum. Mutat. 7, 114–122.CrossRefGoogle Scholar
  12. 12.
    Molchanova, T. P., Pobedimskaya, D. D., and Postnikov, Y. V. (1994) A simplified procedure for sequencing amplified DNA containing the α-2 or α-1 globin gene. Hemoglobin 18, 251.PubMedCrossRefGoogle Scholar
  13. 13.
    Ko, T. M., Tseng, L. H., Hsieh, F. J., and Lee, T. Y. (1993) Prenatal diagnosis of HbH disease due to compound heterozygosity for South-east Asian deletion and Hb Constant Spring by polymerase chain reaction. Prenat. Diag. 13, 143CrossRefGoogle Scholar
  14. 14.
    Baysal, E. (1995) The β-and δ-thalassemia repository. Hemoglobin 19, 213–236.PubMedCrossRefGoogle Scholar
  15. 15.
    Ristaldi, M. S., Pirastu, M., Rosatelli, C., and Cao, A. (1989) Prenatal diagnosis of β-thalassaemia in Mediterranean populations by dot blot analysis with DNA amplification and allele specific oligonucleotide probes. Prenat. Diag. 9, 629–638.CrossRefGoogle Scholar
  16. 16.
    Sutcharitchan, P., Saiki, R., Fucharoen, S., Winichagoon, P., Erlich, H., and Embury, S. H. (1995) Reverse dot-blot detection of Thai β-thalassaemia mutations. Br. J. Haematol. 90, 809.PubMedCrossRefGoogle Scholar
  17. 17.
    Tan, J. A. M. A., Tay, J. S. H., Lin, L. I., et al. (1994) The amplification refractory mutation system (ARMS): a rapid and direct prenatal diagnostic techniques for β-thalassaemia in Singapore. Prenat. Diag. 14, 1077.CrossRefGoogle Scholar
  18. 18.
    Cai, S. P. and Kan, Y. W. (1990) Identification of the multiple β-thalassaemia mutations by denaturing gradient gel electrophoresis. J. Clin. Invest. 85, 550–553.PubMedCrossRefGoogle Scholar
  19. 19.
    Losekoot, M., Fodde, R., Harteveld, C. L., Van Heeren, H., Giordano, P. C., and Bernini, L. F. (1991) Denaturing gradient gel electrophoresis and direct sequencing of PCR amplified genomic DNA: a rapid and reliable diagnostic approach to β thalassaemia. Br. J. Haematol. 76, 269–274.CrossRefGoogle Scholar
  20. 20.
    Craig, J. E., Barnetson, R. A., Prior, J., Raven, J. L., and Thein, S. L. (1994) Rapid detection of deletions causing db thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification. Blood 83, 1673–1682.PubMedGoogle Scholar
  21. 21.
    Weatherall, D. J. and Clegg, J. B. (2001) The Thalassaemia Syndromes, 4th ed. Blackwell, Oxford.CrossRefGoogle Scholar
  22. 22.
    Higgs, D. R. (1993) α-Thalassaemia, in Baillière’s Clinical Haematology. International Practice and Research: The Haemoglobinopathies. (Higgs, D. R. and Weatherall, D. J., eds.) Baillière Tindall, London, p. 117.Google Scholar
  23. 23.
    Old, J. M. (1986) Fetal DNA Analysis, in Genetic Analysis of the Human Disease: A Practical Approach (Davies, K. E., ed.) IRL Press, Oxford, UK, p. 1.Google Scholar
  24. 24.
    Rosatelli, M. C., Tuveri, T., Scalas, M. T., et al. (1992) Molecular screening and fetal diagnosis of β-thalassaemia in the Italian population. Hum. Genet. 89, 585.PubMedGoogle Scholar
  25. 25.
    Decorte, R., Cuppens, H., Marynen, P., and Cassiman, J.-J. (1990) Rapid detection of hypervariable regions by the polymerase chain reaction technique. DNA Cell. Biol. 9, 461–469.PubMedCrossRefGoogle Scholar
  26. 26.
    Camaschella, C., Alfarano, A., Gottardi, E., et al. (1990) Prenatal diagnosis of fetal hemoglobin Lepore-Boston disease on maternal peripheral blood. Blood 75, 2102–2106.PubMedGoogle Scholar
  27. 27.
    Sekizawa, A., Watanabe, A., Kimwa, T. et al. (1996) Prenatal diagnosis of the fetal RhD blood type using a single fetal nucleated erythrocyte from maternal blood. Obstet. Gynaecol. 87, 501–505.CrossRefGoogle Scholar
  28. 28.
    Cheung, M.-C., Goldberg, J. D., and Kan, Y. W. (1996) Prenatal diagnosis of sickle cell anemia and thalassemia by analysis of fetal cells in maternal blood. Nat. Genet. 14, 264–268.PubMedCrossRefGoogle Scholar
  29. 29.
    Kuliev, A., Rechitsky, S., Verlinsky, O., et al. (1999) Birth of healthy children after preimplantation diagnosis of thalassemias. J. Assist. Reprod. Genet. 16, 207–211.PubMedCrossRefGoogle Scholar
  30. 30.
    Old J., Petrou, M., Varnavides, L., Layton, M., and Modell, B. (2000) Accuracy of prenatal diagnosis for hemoglobin disorders in the United Kingdom: twenty-five years experience. Prenat. Diag. 20, 986–991.CrossRefGoogle Scholar
  31. 31.
    Newton, C. R., Graham, A., and Heptinstall, L. E. (1989) Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucl. Acids Res. 17, 2503–2516.PubMedCrossRefGoogle Scholar
  32. 32.
    Kwok, S., Kellogg, D. E., McKinney, N., et al. (1990) Effects of primer-template mismatches on the polymerase chain reaction: human immunodeficiency virus type I model studies. Nucl. Acids Res. 18, 999–1005.PubMedCrossRefGoogle Scholar
  33. 33.
    Kazazian, H. H., Jr. and Boehm, C. D. (1988) Molecular basis and prenatal diagnosis of β-thalassaemia. Blood 72, 1107.PubMedGoogle Scholar
  34. 34.
    Antonarakis, S. E., Boehm, C. D., Diardina, P. J. V., and Kazazian, H. H. J. (1982) Non-random association of polymorphic restriction sites in the β-globin gene cluster. Proc. Natl. Acad. Sci. USA 79, 137–141.PubMedCrossRefGoogle Scholar
  35. 35.
    Chakravarti, A., Buetow, K. H., Antonarakis, S. E., Waber, P. G., Boehm, C. D., and Kazazian, H. H. (1984) Non-uniform recombination within the human β-globin gene cluster. Am. J. Hum. Genet. 71, 79.Google Scholar
  36. 36.
    Orkin, S. H., Little, P. F. R., Kazazian, H. H., Jr., and Boehm, C.D. (1982) Improved detection of the sickle mutation by DNA analysis. N. Engl. J. Med. 307, 32–36.PubMedCrossRefGoogle Scholar
  37. 37.
    Semenza, G. L., Dowling, C. E., and Kazazian, H. H., Jr. (1989) Hinf I polymorphisms 3′ to the human β globin gene detected by the polymerase chain reaction (PCR). Nucl. Acids Res. 17, 2376.PubMedCrossRefGoogle Scholar
  38. 38.
    Faa, V., Rosatelli, M. C., Sardu, R., Meloni, A., Toffoli, C., and Cao, A. (1992) A simple electrophoretic procedure for fetal diagnosis of β-thalassaemia due to short deletions. Prenat. Diag. 12, 903–908.CrossRefGoogle Scholar
  39. 39.
    Waye, J. S., Cai, S.-P., Eng, B., et al. (1991) High haemoglobin A2β0 thalassaemia due to a 532 bp deletion of the 5′ β-globin gene region. Blood 77, 1100–1103.PubMedGoogle Scholar
  40. 40.
    Old, J. M., Varawalla, N. Y., and Weatherall, D. J. (1990) The rapid detection and prenatal diagnosis of beta thalassaemia in the Asian Indian and Cypriot populations in the UK. Lancet 336, 834–837.PubMedCrossRefGoogle Scholar
  41. 41.
    Thein, S. L., Hesketh, C., Brown, K. M., Anstey, A. V., and Weatherall, D. J. (1989) Molecular characterisation of a high A2β thalassaemia by direct sequencing of single strand enriched amplified genomic DNA. Blood 73, 924–930.PubMedGoogle Scholar
  42. 42.
    Dimovski, A. J., Efremove, D. G., Jankovic, L., Plaseska, D., Juricic, D., and Efremov, G. D. (1993) A β0 thalassaemia due to a 1605 bp deletion of the 5′ β-globin gene region. Br. J. Haematol. 85, 143–147.PubMedCrossRefGoogle Scholar
  43. 43.
    Lynch, J. R., Brown, J. M., Best, S., Jennings, M., W., and Weatherall, D. J. (1991) Characterisation of the breakpoint of a 3.5 kb deletion of the β-globin gene. Genomics 10, 509–511.PubMedCrossRefGoogle Scholar
  44. 44.
    Craig, J. E., Kelly, S. J., Barnetson, R., and Thein, S. L. (1992) Molecular characterisation of a novel 10.3 kb deletion causing β-thalassaemia with unusually high HbA2. Br. J. Haematol. 82, 735–744.PubMedCrossRefGoogle Scholar
  45. 45.
    Waye, J. S., Eng, B., and Hunt, J. A., and Chui, D. H. K. (1994) Filipino β-thalassaemia due to a large deletion: identification of the deletion endpoints and polymerase chain reaction (PCR)-based diagnosis. Hum. Genet. 94, 530–532.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • John M. Old
    • 1
  1. 1.National Haemoglobinopathy Reference Laboratory Oxford Haemophilia Centre, Churchill HospitalUniversity of OxfordOxfordUK

Personalised recommendations