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Prenatal Diagnosis of Chromosomal Abnormalities Using Maternal Blood

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Molecular Cytogenetics

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 204))

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Abstract

Fetal chromosomal aneuploidies can be detected by fluorescent in situ hybridization (FISH) analysis of intact fetal cells circulating in maternal blood. Given the low number of circulating fetal cells (1 in 104 to 106 maternal cells) at any given time during pregnancy and given that no fetal-specific markers can unambiguously distinguish maternal from fetal cells, success in fetal cell analysis relies on hybridization and detection efficiency of probes in cells recovered following some formal enrichment. Consequently, many different protocols have been developed using one or more techniques to enrich and improve purity of fetal cells for subsequent FISH. FISH analysis is complicated by enrichment not being 100 percent efficient, yielding heterogeneous mixtures of cell types that require different FISH conditions for optimal signal detection. In addition, certain methods used during enrichment, namely fixation and storage of cells, can adversely affect the quality of cells recovered for FISH analysis. The focus of this chapter will be to highlight variables that impact FISH analysis of fetal cells recovered from maternal blood. Detailed description of the methods developed at Baylor College of Medicine is provided. Recovery of fetal cells for DNA analysis using PCR techniques will not be reviewed; however, several recent reviews are recommended (1–3).

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References

  1. Bianchi D. W. (1999) Fetal cells in the maternal circulation: Feasibility for prenatal diagnosis. Brit. J. Hemat. 105, 574–583.

    Article  CAS  Google Scholar 

  2. Hahn S., Sant R., and Holzgreve W. (1998) Fetal cells in maternal blood: current and future perspectives. Mol. Hum. Reprod. 4, 515–521.

    Article  CAS  PubMed  Google Scholar 

  3. Wachtel S., Shulman L., and Sammons D. (2001) Fetal cells in maternal blood. Clin. Genet. 59, 74–79.

    Article  CAS  PubMed  Google Scholar 

  4. Haddow J. E. (1998) Antenatal screening for Down’s syndrome: Where are we and where next? Lancet 351, 336–337.

    Article  Google Scholar 

  5. Gekas J., Gondry J., Mazur S., et al. (1999) Informed consent to serum screening for Down syndrome: Are women given adequate information? Prenat. Diagn. 19, 1–7.

    CAS  PubMed  Google Scholar 

  6. Goel V., Glazier R., Holzapfel S., et al. (1996). Evaluation of the patient’s knowledge of maternal serum screening. Prenat. Diagn. 16, 425–430.

    Article  CAS  PubMed  Google Scholar 

  7. American College of Obstetricians and Gynecologists. (1996) Maternal serum screening. ACOG Technical Bulletin number 228. Washington DC, ACOG.

    Google Scholar 

  8. Haddow J. E., Palomaki G. E., Knight G. J., et al. (1998) Screening of maternal serum for fetal Down’s syndrome in the first trimester. N. Engl. J. Med. 338, 955–961.

    Article  CAS  PubMed  Google Scholar 

  9. Pergament E. (2000) The application of fluorescence in situ hybridization to prenatal diagnosis. Curr. Opin. Obstet. Gynecol. 12, 73–76.

    Article  CAS  PubMed  Google Scholar 

  10. DeLaCruz F., Shifrin H., Elias S., et al. (1995) Prenatal diagnosis by use of fetal cells isolated from maternal blood. Am. J. Obstet. Gynecol. 173, 1354–1355.

    Article  CAS  Google Scholar 

  11. DeLaCruz F., Shifrin H., Elias S., et al. (1998) Low false-positive rate of aneuploidy detection using fetal cells isolated from maternal blood. Fetal Diagn. Ther. 13, 380.

    Article  CAS  Google Scholar 

  12. AL-Mufti R., Hambley H., Farsaneh F., et al. (1999). Investigation of maternal blood enriched for fetal cells: role in screening and diagnosis of fetal trisomies. Am. J. Med. Genet. 85, 66–75.

    Article  CAS  PubMed  Google Scholar 

  13. Elias S., Price J., Dockter M., et al. (1992) First trimester prenatal diagnosis of trisomy 21 in fetal cells from maternal blood. Lancet 340, 1033.

    Article  CAS  PubMed  Google Scholar 

  14. Bianchi D. W., Mahr A., Zickwolf G. K., et al. (1992) Detection of fetal cells with 47,XY,+21 karyotype in maternal peripheral blood. Hum. Genet. 90, 368–370.

    Article  CAS  PubMed  Google Scholar 

  15. Ganshirt-Ahlert D., Borjesson-Stoll R. M., Dohr A., et al. (1993) Detection of fetal trisomies 21 and 18 from maternal blood using triple gradient and magnetic cell sorting. Am. J. Reprod. Immunol. 30, 194–201.

    CAS  PubMed  Google Scholar 

  16. Cacheux V., Milesi-Fluet C., Tachdjian G., et al. (1992) Detection of 47, XYY trophoblast fetal cells in maternal blood by fluorescent in situ hybridization after using immunomagnetic lymphocyte depletion and flow cytometry sorting. Fetal Diagn. Ther. 7, 190–194.

    Article  CAS  PubMed  Google Scholar 

  17. Pezzolo A., Santi F., Pistoia V., et al. (1997) Prenatal diagnosis of triploidy using fetal cells in maternal circulation. Prenat. Diagn. 17, 389.

    Article  CAS  PubMed  Google Scholar 

  18. Thompson J. S. and Thompson M. W. (editors) Clinical cytogenetics: general principles and autosomal abnormalities. Genetics in Medicine. 5th ed. Philadelphia WB Saunders; 1986. pp. 201–229.

    Google Scholar 

  19. Bischoff F. Z., Lewis D. E., Nguyen D. D., et al. (1998) Prenatal diagnosis with use of fetal cells isolated from maternal blood: five-color fluorescent in situ hybridization analysis on flow-sorted cells for chromosomes X, Y, 13, 18, and 21. Am. J. Obstet. Gynecol. 179, 203–209.

    Article  CAS  PubMed  Google Scholar 

  20. Bischoff F. Z., Lewis D. E., Simpson J. L., et al. (1999) Isolating fetal cells from maternal blood: Strategies to increase sensitivity for fetal aneuploid detection. Am. J. Hum. Genet. 65, A173.

    Google Scholar 

  21. Bischoff F. Z., Lewis D. E., Simpson J. L., et al. (1995) Detection of low-grade mosaicism in fetal cells isolated from maternal blood. Prenat. Diagn. 15, 1182–1184.

    Article  CAS  PubMed  Google Scholar 

  22. Rodriguez de Alba M., Gonzalez-Gonzalez M. C., Palomino P., and Ramos C. (2000) Prenatal diagnosis on fetal cells from maternal peripheral blood in cases of confined placental mosaicism. Prenat. Diagn. 20, 264–265.

    Article  Google Scholar 

  23. Wang J. Y., Zhen D. K., Zilberstein M. E., Falco V. M., and Bianchi D. W. (2000) Non-invasive exclusion of fetal aneuploidy in an at-risk couple with a balanced translocation. Mol. Hum. Reprod. 6, 103–106.

    Article  CAS  PubMed  Google Scholar 

  24. Thomas M. R., Tutschek B., Frost A., et al., (1995) The time of appearance and disappearance of fetal DNA from the maternal circulation. Prenat. Diagn. 15, 641–646.

    Article  CAS  PubMed  Google Scholar 

  25. Lo Y. M. D., Corbetta N., Chamberlain P. F., et al., (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350, 264–265.

    Article  Google Scholar 

  26. Liou J. D., Pao C. C., and Hor J. J. (1993) Fetal cells in the maternal circulation during the first trimester in pregnancies. Hum. Genet. 92, 309–311.

    Article  CAS  PubMed  Google Scholar 

  27. Hamada H., Arinami T., Kubo T., et al. (1993) Fetal nucleated cells in maternal peripheral blood: frequency and relationship to gestational age. Hum. Genet. 91, 427–432.

    Article  CAS  PubMed  Google Scholar 

  28. Lim T. H., Tan A. S., and Goh V. H. (2001) Relationship between gestational age and frequency of fetal trophoblasts and nucleated erythrocytes in maternal peripheral blood. Prenat. Diagn. 21, 14–21.

    Article  CAS  PubMed  Google Scholar 

  29. Rodriguez De Alba M., Palomino P., Gonzalez-Gonzalez C., et al. (2001) Prenatal diagnosis on fetal cells from maternal blood: practical comparative evaluation of the first and second trimesters. Prenat. Diagn. 21, 165–70.

    Article  Google Scholar 

  30. Ciaranfi A., Curchod A., and Odartchenko N. (1977) Postpartum survival of fetal lymphocytes in the maternal blood. Schweiz. Med. Wochenschr. 107, 134–138.

    CAS  PubMed  Google Scholar 

  31. Covone A. E., Johnson P. M., and Mutton D. (1984) Trophoblast cells in peripheral blood of pregnant women. Lancet II, 841–843.

    Article  Google Scholar 

  32. Reading J. P., Huffman J. L., Wu J. C., et al. (1995) Nucleated erythrocytes in maternal blood: quantity and quality of fetal cells in enriched populations. Hum. Reprod. 10, 2510–2515.

    CAS  PubMed  Google Scholar 

  33. Schindler A. M., Graf E., and Martin-Du-Pan R. (1972) Prenatal diagnosis of fetal lymphocytes in the maternal blood. Obstet. Gynecol. 40, 340–346.

    CAS  PubMed  Google Scholar 

  34. Shroder J. and de la Chapelle A. (1972) Fetal lymphocytes in maternal blood. Blood 39, 153–162.

    Google Scholar 

  35. Mueller U. W., Hawes C. S., Wright A. E., et al. (1990) Isolation of fetal trophoblast cells from peripheral blood of pregnant women. Lancet 336, 197–200.

    Article  CAS  PubMed  Google Scholar 

  36. Durrant L., McDowall K., Holmes R, and Liu D. (1996) Non-invasive prenatal diagnosis by isolation of both trophoblasts and fetal nucleated red blood cells from the peripheral blood of pregnant women. Br. J. Obstet. Gynaecol. 103, 219–222.

    Article  CAS  PubMed  Google Scholar 

  37. Hawes C. S., Suskin H. A., Petropoulos A., et al. (1994) A morphologic study of trophoblast isolated from the peripheral blood of pregnant women. Am. J. Obstet. Gynecol. 170, 1297–1300.

    CAS  PubMed  Google Scholar 

  38. Hsieh T. T., Pao C. C., Hor J. J. et al. (1993) Presence of fetal cells in maternal circulation after delivery. Hum. Genet. 92, 204–205.

    Article  CAS  PubMed  Google Scholar 

  39. Bianchi D. W., Zickwolf G. K., Weil G. J., et al. (1996) Male fetal progenitor cells persist in maternal blood for as long as 27 years post partum. Proc. Natl. Acad. Sci. USA 93, 705–708.

    Article  CAS  PubMed  Google Scholar 

  40. Bianchi D. W., Zickwolf G. K., Yih M. C., et al. (1993) Erythroid-specific antibodies enhance detection of fetal nucleated erythrocytes in maternal blood. Prenat. Diagn. 13, 293–300.

    Article  CAS  PubMed  Google Scholar 

  41. Troeger C., Zhong X. Y., Burgemeister R., Minderer S., Tercanli S., Holzgreve W., and Hahn S. (1999) Approximately half of the erythroblasts in maternal blood are of fetal origin. Mol. Hum. Reprod. 5, 1162–1165.

    Article  CAS  PubMed  Google Scholar 

  42. Hall J. M. and Williams S. J. (1992) Isolation and purification of CD34++ fetal cells from maternal blood. Am. J. Hum. Genet. 51, A257.

    Google Scholar 

  43. Bianchi D. W., Williams J. M., Sullivan L. M., et al. (1997) PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies. Am. J. Hum. Genet. 61, 822–829.

    Article  CAS  PubMed  Google Scholar 

  44. Simpson J. L. and Elias S. (1995) Isolating fetal cells in the maternal circulation. Hum. Reprod. Update 1, 409–418.

    Article  CAS  PubMed  Google Scholar 

  45. Holzgreve W., Ghezzi F., DiNaro E., et al. (1998) Feto-maternal cell traffic is disturbed in preeclampsia. Obstet. Gynecol. 91, 669–672.

    Article  CAS  PubMed  Google Scholar 

  46. Al-Mufti R., Hambley H., Albaiges G., Lees C., and Nicolaides K. H. (2000) Increased fetal erythroblasts in women who subsequently develop pre-eclampsia. Hum. Reprod. 15, 1624–1628.

    Article  CAS  PubMed  Google Scholar 

  47. Simchen M. J., Barkai G., Lusky A., and Guetta E. (2001) Fetal hemoglobin-expressing nucleated red blood cell frequencies in pregnancies with intrauterine growth restriction. Prenat. Diagn. 21, 31–35.

    Article  CAS  PubMed  Google Scholar 

  48. Medearis A. L., Hensleigh P. A., Parks D. R., et al. (1984) Detection of fetal erythrocytes in maternal blood post partum with the fluorescence-activated cell sorter. Am. J. Obstet. Gynecol. 148, 290–295.

    CAS  PubMed  Google Scholar 

  49. Nelson J. L., Furst D. E., Maloney S., et al. (1998b) Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. Lancet 351, 559–562.

    Article  CAS  PubMed  Google Scholar 

  50. Bianchi D. W. (2000) Fetal cells in the mother: from genetic diagnosis to diseases associated with fetal cell microchimerism. Eur. J. Obstet. Gynecol. Reprod. Biol. 92, 103–108.

    Article  CAS  PubMed  Google Scholar 

  51. Elias S., Lewis D. E., Simpson J. L., et al. (1996) Isolation of fetal nucleated red blood cells from maternal blood: persistence of cells from prior pregnancy is unlikely to lead to false positive results. J. Soc. Gynecol. Invest. 3, 359A.

    Article  Google Scholar 

  52. Jansen M. W., Brandenburg H., Wildschut H. I., et al. (1997) The effect of chorionic villus sampling on the number of fetal cells isolated from maternal blood and on maternal serum alpha-fetoprotein levels. Prenat. Diagn. 17, 953–959.

    Article  CAS  PubMed  Google Scholar 

  53. Samura O., Sekizawa A., Zhen D. K., Falco V. M., and Bianchi D. W. (2000) Comparison of fetal cell recovery from maternal blood using a high-density gradient for the initial separation step: 1.090 versus 1.119 g/mL. Prenat. Diagn. 20, 281–286.

    Article  CAS  PubMed  Google Scholar 

  54. Sekizawa A., Farina A., Zhen D. K., et al. (1999) Improvement of fetal cell recovery from maternal blood: suitable density gradient for FACS separation. Fetal Diagn. Ther. 14, 229–233.

    Article  CAS  PubMed  Google Scholar 

  55. Troeger C., Holzgreve W., and Hahn S. (1999) A comparison of different density gradients and antibodies for enrichment of fetal erythroblasts by MACS. Prenat. Diagn. 19, 521–526.

    Article  CAS  PubMed  Google Scholar 

  56. Ganshirt-Ahlert D., Burschyk M., Garritsen H. S. P., et al. (1992) Magnetic cell sorting and the transferrin receptor as potential means of prenatal diagnosis from maternal blood. Am. J. Obstet. Gynecol. 166, 1350–1355.

    CAS  PubMed  Google Scholar 

  57. Busch J., Huber P., Pfluger E., et al. (1994) Enrichment of retal cells from maternal blood by high gradient magnetic cell sorting (double MACS) for PCR-based genetic analysis. Prenat. Diagn. 14, 1129–1140.

    Article  CAS  PubMed  Google Scholar 

  58. Steele C. D., Wapner R. J., Smith J. B., et al. (1996) Prenatal diagnosis using fetal cells isolated from maternal blood: a review. Clin. Obstet. Gynecol. 39, 801–813.

    Article  CAS  PubMed  Google Scholar 

  59. Wachtel S. S., Sammons D., Manley M., et al. (1996) Fetal cells in maternal blood: recovery by charge flow separation. Hum. Genet. 98, 162–166.

    Article  CAS  PubMed  Google Scholar 

  60. Price J. O., Elias S., Wachtel S. S., et al. (1991) Prenatal diagnosis using fetal cells from maternal blood by multi-parameter flow cytometry. Am. J. Obstet. Gynecol. 165, 1731–1737.

    CAS  PubMed  Google Scholar 

  61. Sohda S., Arinami T., Hamada H., Nakauchi H., Hamaguchi H., and Kubo T. (1997) The proportion of fetal nucleated red blood cells in maternal blood: estimation by FACS analysis. Prenat. Diagn. 17, 743–752.

    Article  CAS  PubMed  Google Scholar 

  62. Lewis D. E., Schober W., Murrell S., et al. (1996) Rare event selection of fetal nucleated erythrocytes in maternal blood by flow cytometry. Cytometry 23, 218–227.

    Article  CAS  PubMed  Google Scholar 

  63. Wang J. Y., Zhen D. K., Falco V. M., et al. (2000) Fetal nucleated erythrocyte recovery: fluorescence activated cell sorting-based positive selection using anti-gamma globin versus magnetic activated cell sorting using anti-CD45 depletion and anti-gamma globin positive selection. Cytometry 39, 224–230.

    Article  CAS  PubMed  Google Scholar 

  64. Zheng Y. L., DeMaria M. A., Zhen D. K., et al. (1995) Flow sorting of fetal erythroblasts using intracytoplasmic anti-fetal hemoglobin: Preliminary observations on maternal samples. Prenat. Diagn. 15, 897–905.

    Article  CAS  PubMed  Google Scholar 

  65. Serlachius M., Von Koskull H., Wessman M., and Schroder J. (2000) The use of transferrin for enrichment of fetal cells from maternal blood. Prenat. Diagn. 20, 407–410.

    Article  CAS  PubMed  Google Scholar 

  66. DeMaria M. A., Zheng Y. L., Zhen D. K., et al. (1996) Improved fetal nucleated erythrocyte sorting purity using intracellular antifetal hemoglobin and Hoechst 33342. Cytometry 25, 37–45.

    Article  CAS  PubMed  Google Scholar 

  67. Latham S. E., Suskin H. A., Petropoulos A. et al. (1996) A monoclonal antibody to human placental lactogen hormone facilities isolation of fetal cells from maternal in a model system. Prenat. Diagn. 16, 813–821.

    Article  CAS  PubMed  Google Scholar 

  68. Hengstschlager M. and Bernaschek G. (1997) Fetal cells in the peripheral blood of pregnant women express thymidine kinase: a new marker for detection. FEBS. Lett. 404, 299–302.

    Article  CAS  PubMed  Google Scholar 

  69. Zheng Y. L., Zhen D. K., DeMaria M. A., et al. (1997) Search for the optimal fetal cell antibody: results of immunophenoty** studies using flow cytometry. Hum. Genet. 100, 35–42.

    Article  CAS  PubMed  Google Scholar 

  70. Valerio D., Aiello R., and Altieri V. (1997) Isolation of fetal erythroid cells from maternal blood based on expression of erythropoietin receptors. Mol. Hum. Reprod. 3, 451–455.

    Article  CAS  PubMed  Google Scholar 

  71. Bigbee W. L. and Grant S. G. (1994) Use of allele-specific glycophorin A antibodies to enumerate fetal erythroid cells in maternal circulation. Ann. NY. Acad. Sci. 731, 128–132.

    Article  CAS  PubMed  Google Scholar 

  72. Murrell-Bussell S., Nguyen D., Schober W. D., et al. (1998) Optimized fixation and storage conditions for FISH analysis of single-cell suspensions. J. Histochem. Cytochem. 46, 971–974.

    CAS  PubMed  Google Scholar 

  73. Tanke H. J., Oosterwijk J. C., Mesker W. E., et al. (1996) Detection of ‘rare event’ fetal erythroblasts in maternal blood using automated microscopy. Early. Hum. Dev. 47Suppl, S89–S93.

    Article  PubMed  Google Scholar 

  74. Oosterwijk J. C., Knepfle C. F., Mesker W. E., et al. (1998) Strategies for rare-event detection: an approach for automated fetal cell detection in maternal blood. Am. J. Hum. Genet. 63, 1783–1792.

    Article  CAS  PubMed  Google Scholar 

  75. Bischoff F. Z., Marquez-Do D., Nguyen D. D., et al. (2000) Semi-automated screening of nucleated red blood cells for prenatal diagnosis using fetal cells in maternal blood. J. Soc. Gynecol. Investig. 7 Suppl, 180A.

    Google Scholar 

  76. Zheng Y. L., Carter N. P., Price C. M., et al. (1993) Prenatal diagnosis from maternal blood: Simultaneous immunophenoty** and FISH of fetal nucleated erythrocytes isolated by negative magnetic cell sorting. J. Med. Genet. 30, 1051–1056.

    Article  CAS  PubMed  Google Scholar 

  77. Zheng Y. L., Zhen D. K., Farina A., et al. (1999) Fetal cell identifiers: results of microscope slide-based immunocytochemical studies as a function of gestational age and abnormality. Am. J. Obstet. Gynecol. 180, 1234–1239.

    Article  CAS  PubMed  Google Scholar 

  78. Oosterwijk J. C., Mesker W. E., and Ouwerkerk M. C. (1996) Detection of fetal erythroblasts in maternal blood by one-step gradient enrichment and immunocytochemical recognition. Early. Hum. Dev. 47 (suppl), 595–597.

    Article  Google Scholar 

  79. Mesker W. E., Ouwerkerk-van Velzen M. C., Oosterwijk J. C., et al. (1998) Two-colour immunocytochemical staining of gamma (gamma) and epsilon (epsilon) type haemoglobin in fetal red cells. Prenat. Diagn. 18, 1131–1137.

    Article  CAS  PubMed  Google Scholar 

  80. Oosterwijk J. C., Mesker W. E., Ouwerkerk-van Velzen M. C., et al. (1998) Fetal cell detection in maternal blood: a study in 236 samples using erythroblast morphology, DAB and HbF staining, and FISH analysis. Cytometry 32, 178–185.

    Article  CAS  PubMed  Google Scholar 

  81. Oosterwijk J. C., Mesker W. E., Ouwerkerk-van Velzen M. C., et al. (1998) Development of a preparation and staining method for fetal erythroblasts in maternal blood:simultaneous immunocytochemical staining and FISH analysis. Cytometry 32, 170–177.

    Article  CAS  PubMed  Google Scholar 

  82. Mavrou A., Colialexi A., Tsangaris G. T., et al. (1998) Fetal cells in maternal blood: isolation by magnetic cell sorting and confirmation by immunophenoty** and FISH. In Vivo 12, 195–200.

    CAS  PubMed  Google Scholar 

  83. Oosterwijk J. C., Mesker W. E., Ouwerkerkerk-vanVelzen M. C., et al. (1998) Development of a preparation and staining method for fetal erythroblasts in maternal blood: Simultaneous immunocytochemical staining and FISH analysis. Cytometry 32, 170–177.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX

    Farideh Z. Bischoff & Dianne X. Dang

  2. Department of Baylor College of Medicine, Houston, TX

    Dorothy E. Lewis

  3. Departments of Obstetrics and Gynecology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX

    Joe Leigh Simpson

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  1. Farideh Z. Bischoff
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  2. Dianne X. Dang
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  3. Dorothy E. Lewis
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  4. Joe Leigh Simpson
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Editors and Affiliations

  1. London Health Sciences Center, London

    Yao-Shan Fan

  2. The University of Western Ontario, Ontario, Canada

    Yao-Shan Fan

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© 2002 Humana Press Inc.

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Bischoff, F.Z., Dang, D.X., Lewis, D.E., Simpson, J.L. (2002). Prenatal Diagnosis of Chromosomal Abnormalities Using Maternal Blood. In: Fan, YS. (eds) Molecular Cytogenetics. Methods in Molecular Biology™, vol 204. Humana Press. https://doi.org/10.1385/1-59259-300-3:243

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  • DOI: https://doi.org/10.1385/1-59259-300-3:243

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-006-9

  • Online ISBN: 978-1-59259-300-2

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