Summary
Prior to the development of recombinant DNA techniques, the human gene map consisted largely of a set of genes mapped to specific chromosomal locations via analysis of their products in rodent x human hybrid somatic cells. Available markers left large areas of the genome unmapped and in some instances entire chromosomes remained with out a polymorphic marker. It was primarily for this reason that attempts to establish linkages to disease-causing genes were largely unsuccessful. The discovery of restriction fragment length polymorphisms (RFLPs) at the DNA level now renders imminent the generation of a complete human linkage map. In the immediate term this will facilitate the development of carrier detection, pre-symptomatic or diagnostic tests for inherited disorders and in the longer term the isolation, structural and functional analysis of the genes responsible for the cause of the more common hereditary diseases. An outline is presented of the techniques involved in the use of recombinant DNA in diagnostic genetics of the practical applications and implications of this form of technology.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anson, D. S., Choo, K. H., Rees, D. J. G., Gianelli, F., Gould, J., Huddleston, J. A. and Brownlee, G. G. 1984. The gene structure of human antihaemophilic factor IX. EMBO J., 3, 1053–1060.
Antonarakis, S., Kazazian, H. and Orkin, S. 1985. DNA polymorphism and molecular pathology of the human globin gene clusters. Hum. Genet., 69, 1–14.
Bhattacharya, S. S., Wright, A. F., Clayton, J. F., Price, W. H., Phillips, C. I., McKeown, C. M. E., Jay, M., Bird, A. C., Pearson, P. L., Southern, E. M. and Evans, H. J. 1984. Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28. Nature, 309, 253–255.
Bell, G., Selby, J. and Rutter, W. 1982. The highly polymorphic region near the insulin gene is composed of single tandemly repeated sequences. Nature, 295, 31–35.
Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H., and Goeddel, D. V. 1983. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature, 302, 33–37.
Conneally, P. M. 1984. Huntington Disease: Genetics and epidemiology. Am. J. Hum. Genet. 36, 506–526.
Davies, K. E., Pearson, P. L., Harper, P. S., Murray, J. M., O’Brien, T., Sarfarazi, M. and Williamson, R. 1983. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Research, 11, 2303–2312.
Gianelli, F., Choo, K. H., Winship, P. R., Rizza, C. R., Anson, D. S., Rees, D. J. G., Ferrari, N. and Brownlee, G. G. 1984. Characterization and use of an intragenic polymorphism marker for detection of carriers of haemophilia B (factor IX deficiency). Lancet i, 239–241.
Gitschier, J., Drayna, D., Tuddenham, E. G. D., White, R. L. and Lawn, R. M. 1985. Genetic mapping and diagnosis of haemophilia A achieved through a BCI polymorphism in the factor VIII gene. Nature, 314, 738–740.
Gitschier, J., Wood, W. I., Goralka, T. M., Wion, K. L., Chen, E. Y., Eaton, D. H., Vehar, G. A., Capon, D. J. and Lawn, R. M. 1984. Characterization of the human factor VIII gene. Nature, 312, 326–330.
Goodbourn, S. E. Y., Higgs, D. R., Clegg, J. B. and Weatherall, D. J. 1983. Molecular basis of length polymorphism in the human Zeta-globin gene complex. Proc. Nat. Acad. Sci. U.S.A., 80, 5022–5026.
Gusella, J. F., Wexler, N. S., Conneally, P. M., Naylor, S. L., Anderson, M. A., Tanzi, R. E., Watkins, P. C., Ottina, K., Wallace, M. R., Sakaguchi, A. Y., Young, A. B., Shoulson, I., Bonilla, E. and Martin, J. B. 1983. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature, 306, 234–238.
Humphries, P., Barton, D., McKay, A. M., Humphries, M. M., and Carritt, B. 1983. Isolation of a polymorphic segment unique to human chromo some 7 by molecular cloning of hybrid cell DNA. Molec. Gen. Genet., 190, 143–149.
Jeffreys, A. J., Wilson, V. and Thein, S. L. 1985. Hypervariable mini-satellite regions in human DNA. Nature, 314, 67–73.
Kan, Y. W. and Dozy, A. 1978. Polymorphism of DNA sequence adjacent to human Beta-globin structural gene: relationship to sickle mutation. Proc. Nat. Acad. Sci. U.S.A., 75, 5631–5635.
Monaco, A. P., Pertelson, C. J., Middlesworth, W., Colletti, C-A., Aldridge, J., Fischbeck, K. H., Partlett, R., Pericak-Vance, M. A., Roses, A. D. and Kunkel, L. M. 1985. Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment. Nature, 316, 842–845.
Southern, E. M. 1978. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol., 98, 503–517.
White, R., Leppert, M., Bishop, D. T., Barker, D., Berkowitz, J., Brown, C., Callahan, P., Holm, T. and Jerommski, L. 1985. Construction of linkage maps with DNA markers for human chromosomes. Nature, 313, 101–105.
Winship, P. R., Anson, D. S., Rizza, C. R. and Brownlee, G. G. 1984. Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms. Nucleic Acids Research, 12, 8861–8872.
Woo, S. L. C., Lidsky, A. S., Guttler, F., Chandra, T. and Robson, K. J. H. 1983. Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature, 306, 151–155.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Humphries, P. Polymorphic DNA markers genetically linked to disease-causing genes: A review. I.J.M.S. 155, 425–430 (1986). https://doi.org/10.1007/BF02940546
Issue Date:
DOI: https://doi.org/10.1007/BF02940546