Abstract
Since the fall of 1987, PCR technology has had a revolutionary impact upon the prenatal diagnosis of single gene disorders and carrier testing for these disorders. PCR technology has not yet expanded the repertoire of diseases which can be detected, but it has greatly expanded the options of the laboratory diagnostician. At Johns Hopkins it has allowed us to diagnose disorders with greater speed, greater accuracy, and with greater technical flexibility. Examples illustrating each of these improvements follow. Before October 1987, we carried out prenatal diagnosis of sickle cell anemia by Southern blotting for the mutation which usually required two or more weeks from the date of fetal sampling. Since October 1987, we have carried out these diagnoses by PCR techniques in two to four days from fetal sampling. Prior to October 1987, nearly all our prenatal diagnoses of β-thalassemia were accomplished through indirect detection via linked DNA polymorphisms in the β-globin cluster. Again, this work usually took two to four weeks to accomplish. Since October 1987, all our prenatal diagnoses of β-thalassemia have been carried out by direct detection of the disease-producing mutations after PCR amplification of regions of the β-globin gene. These methods provide increased accuracy and diagnosis usually within one week. Improved technical flexibility has meant that 1) if we are unable to determine a β-thalassemia mutation in one parent or another, we can study DNA polymorphisms in the β-globin cluster in a day or two, or 2) we can determine the extent of maternal contamination quickly using sequence differences between mother and fetus. These are just some examples of what PCR has meant to the gene diagnostic enterprise.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Kan, Y.W., and Dozy, A.M. (1978) Proc. Natl. Acad. Sci. USA 75:5631.
Chang, J.C., and Kan, Y.W. (1982) N. Engl. J. Med. 307:30.
Orkin, S.H., Little, P.F.R., Kazazian, H.H., Jr., and Boehm, C.D. (1982) N. Engl. J. Med. 307:32.
Wilson, J.T., Milner, P.F., Summer, M.E., Nallaseth, F.S., Fadel, H.E., et al. (1982) Proc. Natl. Acad. Sci. USA 79:3628.
Pirastu, M., Kan, Y.W., Cao, A., Conner, B.J., Teplitz, R.L., and Wallace, R.B. (1983) N. Engl. J. Med. 309:284.
Saiki, R.K., Chang, C.-A., Levenson, C.H., Warren, T.C., Boehm, C.D., Kazazian, Jr., H.H., and Erlich, H.A. (1988) New Engl. J. Med. 319:537.
Embury, S.H., Lebo, R.V., Dozy, A.M., and Kan, Y.W. (1979) J. Clin. Inv. 63:1307.
denDunnen, J.T., Bakker, E., Klein Breteler, E.G., Pearson, P.L., and van Ommen, G.J.B. (1987) Nature 329:640.
Forrest, S.M., Cross, G.S., Flint, T., Speer, A., Robson, K.J.H., and Davies, K.E. (1988) Genomics 2:109.
Darras, B.T., Blattner, P., Harper, J.F., Spiro, A.J., Alter, S., and Francke, U. (1988) Am. J. Hum. Genet. 43:620.
Gitschier, J., Wood, W.I., Tuddenham, E.G.D., Shuman, M.A., Goralka, T.M., Chen, E.Y., and Lawn, R.M. (1985) Nature 315:427.
Antonarakis, S.E., and Kazazian, H.H., Jr. (1988) Trends in Genet. 4:233.
Friend, S.H., Bernards, R., Rogel, J., Weinberg, R.A., Rapaport, J.M., Albert, D.M., and Dryja, T.P. (1986) Nature 323:643.
Saiki, R.K., Bugawan, T.L., Horn, G.T., Mullis, K.B., and Erlich, H.A. (1987) Nature 324:163.
Kogan, S.C., Doherty, M., and Gitschier, J. (1987) N. Engl. J. Med. 317:985.
Chelab, F., Dogerty, M., Cai, S., Kan, Y.W., Cooper, S., and Rubin, E. (1987) Nature 329:293.
Wong, C., Dowling, E.E., Saiki, R.K., Higuchi, R., Erlich, H.A., and Kazazian, H.H., Jr. (1987) Nature 330:384.
Engelke, D.R., Honer, P.A., and Collins, F.S. (1988) Proc. Natl. Acad. Sci. USA 85:544.
Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.T., Mullis, K.B., and Erlich, H.A. (1988) Science 239:489.
Kazazian, H.H., Jr., and Boehm, C.D. (1988) Blood 72:1107.
Gonzalez-Redondo, J.M., Stoming, T.A., Lanclos, K.D., Gy, U.C., Kutlar, A., Kutlar, F., Nalcatsuji, T., Deng, B., Han, I.S., McKie, V.C., and Huisman, T.J.H. (1988) Blood 72:1007.
Spritz, R.A., and Orkin, S.H. (1982) Nucl. Acids Res. 10:8025.
Chamberlain, J.S., Gibbs, R.A., Ranier, J.E., Nguyen, P.N., Farwell, NJ., and Caskey, C.T. Nucl. Acids Res., in press.
Koenig, M., Hoffman, E.P., Bertelson, C.J., Monaco, A.P., Feener, C., and Kunkel, L.M. (1987) Cell 50:509.
Mullis, K.B., and Faloona, F. (1987) Meth. in Enzymol. 155:35.
Feldman, G.L., Williamson, R., Beaudet, A.L., and O’Brien, W.E. (1988) Lancet ii:102.
Feldman, G.L., O’Brien, W.E., Durtschi, B., Gardner, P., Williamson, R., and Beaudet, A.L. (1988) Am. J. Hum. Genet. 43:A83 (abstract).
Brock, D.J.H., Mcintosh, I., Curtis, A., and Millan, F.A. (1988) Am. J. Hum. Genet.43:A79 (abstract).
Myerowitz, R. (1988) Proc. Natl. Acad. Sci. USA 85:3955.
Arpaia, E., Dumbrille-Ross, A., Maler, T., et al. (1988) Nature 333:85.
Myerowitz, R., and Costigan, F.C. (1988) J. Biol. Chem. 263:18587.
DiLella, A.G., Marvit, J., Lidsky, A.S., Guttler, F., and Woo, S.L.C. (1986) Nature 322:799.
DiLella, A.G., Marvit, J., Brayton, K., and Woo, S.L.C. (1987) Nature 327:333.
Sheffield, V.C., Cox, D.R., Lerman, S.L., and Myers, R.M. Proc. Natl. Acad. Sci. USA, in press.
Saiki, R.K., Walsh, P.S., Levenson, C.H., and Erlich, HA. (1989) Proc. Nail. Acad. Sci. USA, in press.
Editor information
Editors and Affiliations
Copyright information
© 1989 Stockton Press
About this chapter
Cite this chapter
Kazazian, H.H. (1989). Use of PCR in the Diagnosis of Monogenic Disease. In: Erlich, H.A. (eds) PCR Technology. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-20235-5_14
Download citation
DOI: https://doi.org/10.1007/978-1-349-20235-5_14
Publisher Name: Palgrave Macmillan, London
Print ISBN: 978-0-333-48948-2
Online ISBN: 978-1-349-20235-5
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)