Molecular Genetic Techniques for Prenatal Diagnosis

  • John A. PhillipsIII


Molecular genetic techniques have clarified the DNA abnormalities that cause a variety of genetic disorders. Use of restriction endonucleases, Southern blots, and DNA hybridization has made it possible to detect several types of hemoglobinopathies routinely as early as 8–10 weeks after conception. These types of studies are now being applied to the prenatal diagnosis of a growing number of other genetic disorders. Further developments will bring wider applicability and increased sensitivity, and the number and variety of disorders that will be detectable make knowledge of these tools pertinent to almost every medical subspeciality.


Prenatal Diagnosis Duchenne Muscular Dystrophy Osteogenesis Imperfecta Congenital Adrenal Hyperplasia Huntington Disease 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Antonarakis, S. E., Phillips III, J. A., and Kazazian, Jr., H. H., 1982, Genetic diseases: Diagnosis by restriction endonuclease analysis, J. Pediatr. 100:845.PubMedCrossRefGoogle Scholar
  2. Antonarakis, S. E., Carpenter, Jr., R. J., and Hoyer, L. W., et al., 1985, Prenatal diagnosis of haemophilia A by factor VIII gene analysis, Lancet 1:1407.PubMedCrossRefGoogle Scholar
  3. Bakker, E., Goor, N., and Wrogemann, K., et al., 1985, Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs, Lancet 1:655.PubMedCrossRefGoogle Scholar
  4. Barsh, G., Seeburg, P., and Gelinas, R., 1983, Structure and expression of the human growth hormone-like gene cluster. Nucleic Acid Res. 11:3939.PubMedCrossRefGoogle Scholar
  5. Batshaw, M. L., Brusilow, S., and Waber, L., et al., 1982, Treatment of inborn errors of urea synthesis, N. Engl. J. Med. 306:1387.PubMedCrossRefGoogle Scholar
  6. Bear, J. C., McManamon, P., and Morgan, J., et al., 1984, Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: Data for genetic counseling, Am. J. Med. Genet. 18:45.PubMedCrossRefGoogle Scholar
  7. Beaudet, A. L., 1984, Bibliography of cloned human and other selected DNAs, Am. J. Hum. Genet. 36:235.Google Scholar
  8. Bhattacharya, S. S., Wright, A. F., and Clayton, J. F., et al., 1984, Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28, Nature 309:253.PubMedCrossRefGoogle Scholar
  9. Biggs, R., 1983, Defects in coagulation, in: Principles and Practice of Medical Genetics (A. E. H. Emery and D. L. Rimoin, eds.), p. 1068, Churchill Livingstone, Edinburgh.Google Scholar
  10. Boehm, C. D., and Kazazian, H. H., 1984, Error in prenatal diagnosis by DNA analysis, N. Engl. J. Med. 311:58.PubMedGoogle Scholar
  11. Boehm, C. D., Antonarakis, S. E., and Philipps, J. A. III, et al., 1983, Prenatal diagnosis using DNA polymorphisms, N. Engl. J. Med. 308:1054.PubMedCrossRefGoogle Scholar
  12. Botstein, D., White, R. L., and Skolnick, M., et al., 1980, Construction of a genetic linkage map in man using restriction fragment length polymorphisms, Am. J. Hum. Genet. 32:314.PubMedGoogle Scholar
  13. Boué, J., Oberle, L, and Heilig, R., et al., 1985, First trimester prenatal diagnosis of adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis to a DNA probe, Hum. Genet. 69:272.PubMedCrossRefGoogle Scholar
  14. Byers, P. H., Siegel, R. C., and Peterson, K. E., et al., 1981, Marfan syndrome: Abnormal α2 chain in type I collagen, Proc. Natl. Acad. Sci. USA 78:7745.PubMedCrossRefGoogle Scholar
  15. Camerino, G., Mattei, M. G., Mettei, J. F., et al., 1983, Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male, Nature 306:701.PubMedCrossRefGoogle Scholar
  16. Carroll, M. C., Campbell, R. D., and Porter, R. R., 1985, Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man, Proc. Natl. Acad. Sci. USA 82:521.PubMedCrossRefGoogle Scholar
  17. Choo, K. H., Gould, K. G., and Rees, D. J. G., et al., 1982, Molecular cloning of the gene for human anti-haemophilic factor IX, Nature 299:178.PubMedCrossRefGoogle Scholar
  18. Dalgaard, O. Z., 1957, Bilateral polycystic disease of the kidneys. A follow-up of 284 patients and their families, Acta. Med. Scand. 328(suppl.):1.Google Scholar
  19. Davies, K. E., Pearson, P. L., and Harper, P. S., et al., 1983, Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome, Nucleic Acid Res. 11:2303.PubMedCrossRefGoogle Scholar
  20. Deisseroth, A., Nienhuis, A., and Turner, P., et al., 1977, Localization of the human α-globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization assay, Cell 12:205.PubMedCrossRefGoogle Scholar
  21. Deisseroth, A., Nienhuis, A., and Lawrence, J., et al., 1978, Chromosomal localization of human β-globin gene on human chromosome 11 in somatic cell hybrids, Proc. Natl. Acad. Sci. USA 75:1456.PubMedCrossRefGoogle Scholar
  22. Disteche, C., Luthy, D., and Haslam, D. B., et al., 1984, Prenatal identification of a deleted Y chromosome by cytogenetics and a Y-specific repetitive DNA probe, Hum. Genet. 67:222.PubMedCrossRefGoogle Scholar
  23. Drayna, D., Davies, K., and Hartley, D., et al., 1984, Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms, Proc. Natl. Acad. Sci. USA 81:2836.PubMedCrossRefGoogle Scholar
  24. Dupont, B., Oberfield, S. E., and Smithwick, E. M., et al., 1977, Close genetic linkage between HLA and congenital adrenal hyperplasia (21-hydroxylase deficiency), Lancet 2:1309.PubMedCrossRefGoogle Scholar
  25. Eiberg, H., Mohr, J., and Nielsen, L. S., et al., 1983, Genetics and linkage relationships of C3 polymorphism: Discovery of C3-Se linkage and assignment of LES-C3-DM-Se-PEPD-Lu synteny to chromosome 19, Clin. Genet. 24:159.PubMedCrossRefGoogle Scholar
  26. Eiberg, H., Mohr, J., and Schmiegelow, L. S., et al., 1985, Linkage relationships of paraoxonase (PON) with other markers: indication of PON-cystic fibrosis synteny, Clin. Genet. 28:265.PubMedCrossRefGoogle Scholar
  27. Emery, A. E. H., 1983, The muscular dystrophies, in: Principles and Practice of Medical Genetics (A. E. H. Emery and D. L. Rimoin, eds.), p. 396, Churchill Livingstone, Edinburgh.Google Scholar
  28. Ewens, W. J., Spielman, R. S., and Harris, H., 1981, Estimation of genetic variation at the DNA level from restriction endonuclease data, Proc. Natl. Acad. Sci. USA 78:3748.PubMedCrossRefGoogle Scholar
  29. Farrall, M., Rodeck, C. H., Stanier, P., et al., First-trimester prenatal diagnosis of cystic fibrosis with linked DNA probes. Lancet 1:1402, 1986.PubMedCrossRefGoogle Scholar
  30. Fearon, E. R., Mallonee, R. L., and Phillips, J. A., III, et al., 1985, Genetic analysis of carbamyl phosphate synthetase I deficiency, Hum. Genet. 70:207.PubMedCrossRefGoogle Scholar
  31. Folstein, S. E., Phillips, J. A., III, Meyers, D. A., et al., 1985, Huntington’s disease: Two families with differing clinical features show linkage to the G8 probe, Science 209: 776.CrossRefGoogle Scholar
  32. Giannelli, F., Choo, K. H., and Rees, D. J. G., et al., 1983, Gene deletions in patients with hemophilia B and anti-factor IX antibodies, Nature 303:181.PubMedCrossRefGoogle Scholar
  33. Giannelli, F., Choo, K. H., and Winship, P. R., et al., 1984, Characterization and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency), Lancet 1:239.PubMedCrossRefGoogle Scholar
  34. Gibbs, D. A., Crawfurd, M. D’A., and Headhouse-Benson, C. M., et al., 1984, First trimester diagnosis of Lesch-Nyhan syndrome, Lancet 2:1180.PubMedCrossRefGoogle Scholar
  35. Gitschier, J., Wood, W. I., and Goralka, T. M., et al., 1984, Characterization of the human factor VIII gene, Nature 312:326.PubMedCrossRefGoogle Scholar
  36. Gitschier, J., Drayna, D., and Tuddenham, E. G. D., et al., 1985, Genetic mapping and diagnosis of haemophilia A achieved through a BclI polymorphism in the factor VIII gene, Nature 314:738.PubMedCrossRefGoogle Scholar
  37. Gosden, J. R., Mitchell, A. R., and Gosden, C. M., et al., 1982, Direct vision chorion biopsy and chromosome specific probes for determination of fetal sex in first trimester prenatal diagnosis, Lancet 11:1416.CrossRefGoogle Scholar
  38. Gosden, J. R., Gosden, C. M., and Christie, S., et al., 1984a, The use of cloned Y-chromosome-specific DNA probes for fetal sex determination in first trimester prenatal diagnosis, Hum. Genet. 66:347.PubMedCrossRefGoogle Scholar
  39. Gosden, J. R., Christie, S., and Gosden, C. M., et al., 1984b, Rapid fetal sex determination in first trimester prenatal diagnosis by dot hybridization of DNA probes, Lancet 1:540.PubMedCrossRefGoogle Scholar
  40. Grunebaum, L., Cazenave, J.-P., and Camerino, G., et al., 1984, Carrier detection of hemophilia B using a restriction site polymorphism associated with the coagulation factor IX gene, J. Clin. Invest. 73:1491.PubMedCrossRefGoogle Scholar
  41. Gusella, J. F., Wexler, N. S., and Conneally, P. M., et al., 1983, A polymorphic DNA marker genetically linked to Huntington’s disease, Nature 306:234.PubMedCrossRefGoogle Scholar
  42. Harper, K., Pembrey, M. E., and Davies, K. E., et al., 1984, A clinically useful DNA probe closely linked to Haemophilia A, Lancet 2:6.PubMedCrossRefGoogle Scholar
  43. Harper, P. S., 1983, Myotonic dystrophy and related disorders, in: Principles and Practice of Medical Genetics (A. E. H. Emery and D. L. Rimoin, eds.), p. 426, Churchill Livingstone, Edinburgh.Google Scholar
  44. Harper, P. S., 1984, DNA markers and Duchenne muscular dystrophy, Arch. Dis. Child. 59:195.PubMedCrossRefGoogle Scholar
  45. Henke, E., Leader, M., and Tajima, S., et al., 1985, A 38 base pair insertion in the pro α2(I) collagen gene of a patient with Marfan syndrome, J. Cell. Biochem. 27:169.PubMedCrossRefGoogle Scholar
  46. Heckenlively, J., 1983, The hereditary retinal and choroidal degenerations, in: Principles and Practice of Medical Genetics (A. E. H. Emery, and D. L. Rimoin, eds.), p. 522, Churchill-Livingstone, Edinburgh.Google Scholar
  47. Holzgreve, W., and Golbus, M. S., 1984, Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy, Am. J. Hum. Genet. 36:320.PubMedGoogle Scholar
  48. Humphries, S. E., and Williamson, R., 1983, Application of recombinant DNA technology to prenatal detection of inherited defects, Brit. Med. Bull. 39:343.PubMedGoogle Scholar
  49. Janco, R. L., Phillips, J. A., III, and Orlando, P., et al., 1986, Carrier testing strategy in haemophilia A, Lancet I:148.CrossRefGoogle Scholar
  50. Jeffreys, A. J., 1979, DNA sequence variants in the Gγ-, Aγ-, δ- and β-globin genes of man, Cell 18:1.PubMedCrossRefGoogle Scholar
  51. Kan, Y. W., and Dozy, A. M., 1978, Antenatal diagnosis of sickle cell anemia by DNA analysis of amniotic fluid cells, Lancet 2:910.PubMedGoogle Scholar
  52. Kidd, V. J., and Woo, S. L. C., 1984, Recombinant DNA probes used to detect genetic disorders of the liver, Hepatology 4:731.PubMedCrossRefGoogle Scholar
  53. Kidd, V. J., Wallace, R. B., Itakura, K., et al., 1983, α1-Antitrypsin deficiency detection by direct analysis of the mutation in the gene, Nature 304:230.PubMedCrossRefGoogle Scholar
  54. Knowlton, R. G., Cohen-Haguenauer, O., and Van Cong, N., et al., 1985, A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7, Nature 318:380.PubMedCrossRefGoogle Scholar
  55. Kohne, D. E., Levinson, S. A., and Byers, M. J., 1977, Room temperature method for increasing the rate of DNA reassociation by many thousandfold: The phenol emulsion, reassociation technique, Biochemistry 16:5329.PubMedCrossRefGoogle Scholar
  56. Krumlauf, R., Jeanpierre, M., and Young, B. D., 1982, Construction and characterization of genomic libraries from specific human chromosomes, Proc. Natl. Acad. Sci. USA 79:2971.PubMedCrossRefGoogle Scholar
  57. Kuhnle, U., Chow, D., and Rapaport, R., et al., 1981, The 21-hydroxylase activity in the glomerulosa and faciculata of the adrenal cortex in congenital adrenal hyperplasia, J. Clin. Endocrinol. Metab. 52:534.PubMedCrossRefGoogle Scholar
  58. Kunkel, L. M., Monaco, A. P., and Middlesworth, W., et al., 1985, Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion, Proc. Natl. Acad. Sci. (USA) 82:4778.CrossRefGoogle Scholar
  59. Kurachi, K., and Davie, E. W., 1982, Isolation and characterization of cDNA coding for human factor IX, Proc. Natl. Acad. Sci. USA 79:6461.PubMedCrossRefGoogle Scholar
  60. Kurnit, D. M., and Hoehn, H., 1979, Prenatal diagnosis of human genome variation, Annu. Rev. Genet. 13:235.PubMedCrossRefGoogle Scholar
  61. Latt, S. A., Kunkel, L. M., and Tantravahi, U., et al., 1983, Construction, analysis, and utilization of recombinant phage libraries obtained using fluorescence activated flow sorting in recombinant phage libraries, in: Recombinant DNA and Medical Genetics (A. Messer and I. H. Porter, eds.), p. 35, Academic Press, New York.Google Scholar
  62. Lau, Y.-F., Dozy, A. M., and Huang, J. C., et al., 1984, A rapid screening test for antenatal sex determination, Lancet 1:14.PubMedCrossRefGoogle Scholar
  63. Laurell, C.-B., and Sveger, T., 1975, Mass screening of newborn Swedish infants for al antitrypsin deficiency, Am. J. Hum. Genet. 27:213.PubMedGoogle Scholar
  64. Leary, J. J., Brigati, D. J., and Ward, D., 1983, Rapid and sensitive colorimetric method for visualizing biotin-labeled DNA probes hybridized to DNA or RNA immobilized on nitrocellulose: Bio blots, Proc. Natl. Acad. Sci. USA 80:4045.PubMedCrossRefGoogle Scholar
  65. Lewin, B., 1983, What is a gene? A biochemical view, in: Genes, p. 21, Wiley, New York.Google Scholar
  66. Lidsky, A. S., Guttler, F., and Woo, S. L. C., 1985, Prenatal diagnosis of classic phenylketonuria by DNA analysis, Lancet 2:549.CrossRefGoogle Scholar
  67. Lindenbaum, R. H., Clarke, G., and Patel, C., et al., 1979, Muscular dystrophy in an X;l translocation female suggests that Duchenne locus is on X chromosome short arm, J. Med. Genet. 16:389.PubMedCrossRefGoogle Scholar
  68. Malcolm, A. D. B., 1981, The use of restriction enzymes in genetic engineering, Genet. Eng. 2:129.Google Scholar
  69. Maniatis, T., Fritsch, E. F., and Laver, J., et al., 1980, The molecular genetics of human hemoglobins, Annu. Rev. Genet. 14:145.PubMedCrossRefGoogle Scholar
  70. McKusick, V. A., 1983, The human gene map, in: Mendelian Inheritance in Man, p. xxxvii, Johns Hopkins University Press, Baltimore.Google Scholar
  71. Migeon, B. R., Moser, H. W., and Moser, A. B., et al., 1981, Adrenoleukodystrophy: Evidence for X linkage, inactivation and selection favoring the mutant allele in heterozygous cells, Proc. Natl. Acad. Sci. USA 78:5066.PubMedCrossRefGoogle Scholar
  72. Mohr, J., 1954, A Linkage Study in Man, Munksgard, Copenhagen.Google Scholar
  73. Monaco, A. P., Bertelson, C. J., and Middlesworth, W., et al., 1985, Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment, Nature 316:842.PubMedCrossRefGoogle Scholar
  74. Morton, C. C., Kirsch, I. R., Nance, W. E., et al., 1984, Orientation of loci within the human major histocompatibility complex by chromosomal in situ hybridization, Proc. Natl. Acad. Sci. USA 81:1816.Google Scholar
  75. Msall, M., Batshaw, M. L., and Suss, R., et al., 1984, Neurologic outcome in children with inborn errors of urea synthesis, N. Engl. J. Med. 310:1500.PubMedCrossRefGoogle Scholar
  76. Mulligan, L. M., Phillips, M. A., and Forster-Gibson, C. J., et al., 1985, Genetic mapping of DNA segments relative to the locus for the fragile-X syndrome at Xq27.3, Am. J. Hum. Genet. 37:463.PubMedGoogle Scholar
  77. Murray, J. M., Davies, K. E., and Harper, P. S., et al., 1982, Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy, Nature 300:69.PubMedCrossRefGoogle Scholar
  78. Oberle, I., Camerino, G., and Heilig, R., 1985a, Genetic screening for hemophilia A (classic hemophilia) with a polymorphic DNA probe, N. Engl. J. Med. 312:682.PubMedCrossRefGoogle Scholar
  79. Oberle, I., Mandel, J. L., and Boué, J., et al., 1985b, Polymorphic DNA markers in prenatal diagnosis of fragile X syndrome, Lancet 1:871.PubMedCrossRefGoogle Scholar
  80. Old, J. M., Purvis-Smith, S., and Wilcken, B., 1985, Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis, Lancet 1:73.PubMedCrossRefGoogle Scholar
  81. Phillips, J. A., III, Hjelle, B. L., and Seeburg, P. H., et al., 1981, Molecular basis for familial isolated growth hormone deficiency, Proc. Natl. Acad. Sci. USA 78:6372.PubMedCrossRefGoogle Scholar
  82. Razin, A., and Riggs, A. D., 1980, DNA methylation and gene function, Science 210:604.PubMedCrossRefGoogle Scholar
  83. Reeders, S. T., Breuning, M. H., and Davies, K. E., et al., 1985, A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16, Nature 317:542.PubMedCrossRefGoogle Scholar
  84. Rivarola, M. A., Phillips, J. A., III, and Migeon, C. J., et al., 1984, Phenotypic heterogeneity in familial isolated growth hormone deficiency (IGHD) type 1A, J. Clin. Endocrinol. Metab. 59:34.PubMedCrossRefGoogle Scholar
  85. Rodeck, C. H., and Morsman, J. M., 1983, First-trimester chorion biopsy, Brit. Med. Bull. 39:338.PubMedGoogle Scholar
  86. Rodeck, C. H., Patrick, A. D., Pembrey, M. E., et al., 1982, Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency, Lancet 2:297.PubMedCrossRefGoogle Scholar
  87. Rohme, D., Fox, H., Herrmann, B., et al., 1984, Molecular clones of the mouse t complex from micro-dissected metaphase chromosomes, Cell 36:783.PubMedCrossRefGoogle Scholar
  88. Rozen, R., Fox, J., and Fenton, W. A., 1985, Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus, Nature 313:815.PubMedCrossRefGoogle Scholar
  89. Scriver, C. R., and Clow, C. L., 1980, Phenylketonuria and other phenylalanine hydroxylation mutants in man, Ann. Rev. Genet. 14:179.PubMedCrossRefGoogle Scholar
  90. Shapiro, S. S., 1984, Genetic predisposition to inhibitor formation, in: Factor VIII Inhibitors (L. W. Hoyer, ed.), p. 45, Liss, New York.Google Scholar
  91. Shaw, D. J., Meredith, A. L., and Sarfarazi, M., et al., 1985, The apolipoprotein CII gene: Sub-chromosomal localization and linkage to the myotonic dystrophy locus, Hum. Genet. 70:271.PubMedCrossRefGoogle Scholar
  92. Southern, E., 1975, Detection of specific sequences among DNA fragments separated by gel electrophoresis, J. Molec. Biol. 98:503.PubMedCrossRefGoogle Scholar
  93. Steel, C. M., 1984a, DNA in medicine, The tools (Part I), Lancet 2:908.PubMedCrossRefGoogle Scholar
  94. Steel, C. M., 1984b, DNA in medicine, The tools (Part II), Lancet 2:966–968.PubMedCrossRefGoogle Scholar
  95. Su, T.-S., Bock, H.-G. O., and Beaudet, A. L., et al., 1982, Molecular analysis of argininosuccinate synthetase deficiency in human fibroblasts, J. Clin. Invest. 70:1334.PubMedCrossRefGoogle Scholar
  96. Su, T.-S., Beaudet, A. L., and O’Brien, W. E., 1983, Abnormal mRNA for argininosuccinate synthetase in citrullinaemia, Nature 301:533.PubMedCrossRefGoogle Scholar
  97. Szabo, P., Purrello, M., and Rocchi, M., et al., 1984, Cytological mapping of the human glucose-6-phosphate dehydrogenase gene distal to the fragile-X site suggests a high rate of meiotic recombination across this site, Proc. Natl. Acad. Sci. USA 81:7855.PubMedCrossRefGoogle Scholar
  98. Tommerup, N., Sondergaard, F., and Tonnesen, T., et al., 1985, First trimester prenatal diagnosis of a male fetus with fragile X, Lancet 1:870.PubMedCrossRefGoogle Scholar
  99. Tonnesen, T., Sondergaard, F., and Mikkelsen, M., et al., 1984a, X-chromosome-specific probe DX13 for carrier detection and first trimester prenatal diagnosis in haemophilia A, Lancet 2:1269.PubMedCrossRefGoogle Scholar
  100. Tonnesen, T., Sondergaard, F., and Guttler, F., et al., 1984b, Exclusion of haemophilia B in male fetus by chorionic villus biopsy, Lancet 2:932.PubMedCrossRefGoogle Scholar
  101. Tsipouras, P., Myers, J. C., and Ramirez, F., et al., 1983, Restriction fragment length polymorphism associated with the pro α2(I) gene of human type I procollagen: Application to a family with an autosomal dominant form of osteogenesis imperfecta, J. Clin. Invest. 72:1262.PubMedCrossRefGoogle Scholar
  102. Tsui, L.-C., Buchwald, M., and Barker, D., et al., 1985, Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker, Science 230:1054.PubMedCrossRefGoogle Scholar
  103. Tyler, A., and Harper, P. S., 1983, Attitudes of subjects at risk and their relatives towards genetic counselling in Huntington’s chorea, J. Med. Genet. 20:179.PubMedCrossRefGoogle Scholar
  104. Wainwright, B. J., Scambler, P. J., and Schmidtke, J., et al., 1985, Localization of cystic fibrosis locus to human chromosome 7cenq22, Nature 318:384.PubMedCrossRefGoogle Scholar
  105. Warren, S. T., Glover, T. W., and Davidson, R. L., et al., 1985, Linkage and recombination between fragile X-linked mental retardation and the factor IX gene, Hum. Genet. 69:44.PubMedCrossRefGoogle Scholar
  106. Watson, J. D., and Crick, F. H. C., 1953, Molecular structure of nucleic acids, Nature 171:737.PubMedCrossRefGoogle Scholar
  107. White, P. C., New, M. I., and Dupont, B., 1984a, HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation, Proc. Natl. Acad. Sci. USA 81:7505.PubMedCrossRefGoogle Scholar
  108. White, P. C., Grossberger, D., and Onufer, B. J., et al., 1985, Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man, Proc. Natl. Acad. Sci. 82:1089.PubMedCrossRefGoogle Scholar
  109. White, R., Leppert, M., and Bishop, D. T., et al., 1985, Construction of linkage maps with DNA markers for human chromosomes, Nature 313:101.PubMedCrossRefGoogle Scholar
  110. White, R., Woodward, S., and Leppert, M., et al., 1985, A closely linked genetic marker for cystic fibrosis, Nature 318:382.PubMedCrossRefGoogle Scholar
  111. Williams, C. J., and Prockop, D. J., 1983, Synthesis and processing of a type 1 procollagen containing shortened pro α(I) chains by fibroblasts from a patient with osteogenesis imperfecta, J. Biol. Chem. 258:5915.PubMedGoogle Scholar
  112. Woo, S. L. C., 1984, Prenatal diagnosis and carrier detection of classic phenylketonuria by gene analysis, Pediatrics 74:412.PubMedGoogle Scholar
  113. Woo, S. L. C., Lidsky, A. S., and Guttler, F., et al., 1983, Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria, Nature 306:151.PubMedCrossRefGoogle Scholar
  114. Zatz, M., Vianna-Morgante, A. M., and Campos, D., et al., 1981, Translocation (X;6) in a female with Duchenne muscular dystrophy: Implications for the localization of the DMD locus, J. Med. Genet. 18:442.PubMedCrossRefGoogle Scholar

Copyright information

© Aubrey Milunsky 1986

Authors and Affiliations

  • John A. PhillipsIII
    • 1
  1. 1.Department of Pediatrics, Division of GeneticsVanderbilt University School of MedicineNashvilleUSA

Personalised recommendations