Abstract
From a chromosome 21 phage library, we selected 10 clones located proximal of the senile plaque amyloid precursor protein gene. Since a locus for Alzheimer's disease (AD) has been localized in the pericentromeric region of chromosome 21, the selected phage clones are potential candidate probes for genetic analysis of AD. In this study, we subcloned single-copy fragments of the selected phage clones, refined their physical localization, and examined their chromosomal distribution in relation to their position on chromosome 21. The results indicated that the phage clones are identifying nine chromosome 21 loci, which, if polymorphic, may be helpful in localizing the AD locus more precisely. Moreover, since all phage clones are located close to the centromere of chromosome 21, they can be used to determine the parental origin of nondisjunction in trisomy 21 with high reliability.
Similar content being viewed by others
Literature cited
Terry, R.D., and Katzmann, M.D. (1983).Ann. Neurol. 14497–506.
Fitch, N., Becker, R., and Heller, A. (1988).Ann. Neurol. 2314–19.
Davies, P. (1986).Neurobiol. Aging 7459–466.
Mann, D.M.A. (1988).Mech. Ageing Dev. 4399–136.
Patterson, D., Gardiner, K., Kao, F., Tanzi, R., Watkins, P., and Gusella, J.F. (1988).Proc. Natl. Acad. Sci. U.S.A. 858266–8270.
St George-Hyslop, P.H., Tanzi, R., Polinsky, R.J., Haines, J.L., Nee, L., Watkins, P.C., Myers, R.H., Feldman, R.G., Pollen, D., Drachman, D., Growdon, J., Bruni, A., Foncin, J.F., Salmon, D., Frommetl, P., Amaducci, L., Sorbi, S., Piacentini, S., Stewart, G.D., Hobbs, W.J., Conneally, P.M., and Gusella, J.F. (1987).Science 235885–890.
Van Broeckhoven, C., Genthe, A.M., Vandenberghe, A., Horsthemke, B., Backhovens, H., Raeymaekers, P., Van Hul, W., Wehnert, A., Gheuens, J., Cras, P., Bruyland, M., Martin, J-J., Salbaum, M., Multhaup, G., Masters, C.L., Beyreuther, K., Gurling, H.M.D., Mullan, M.J., Holland, A., Barton, A., Irving, N., Williamson, R., Richards, S.J., and Hardy, J.A. (1987).Nature 329153–155.
Tanzi, R.E., St George-Hyslop, P.H., Haines, J.L., Polinsky, R.J., Nee, L., Foncin, J.F., Neve, R.L., McClatchey, A.I., Conneally, P.M., and Gusella, J.F. (1987).Nature 329156–157.
Van Broeckhoven, C., Van Hul, W., Backhovens, H., Raeymaekers, P., Van Camp, G., Stinissen, P., Wehnert, A., De Winter, G., Gheuens, J., and Vandenberghe, A. (1988). InGenetics and Alzheimer's Disease. (eds.) Sinet, P.M., Lamour, Y., Christen, Y. (Springer-Verlag, Berlin), pp. 124–129.
Goate, A.M., Owen, M.J., James, L.A., Mullan, M.J., Rossor, M.N., Haynes, A.R., Farral, M., Lai, L.Y.C., Roques, P., Williamson, R., and Hardy, J.A. (1989).Lancet 1352–355.
Tanzi, R.E., Haines, J.L., Watkins, P.C., Stewart, G.D., Wallace, M.R., Hallewel, R., Wong, C., Wexler, N.S., Conneally, P.M., and Gusella, J.F., (1988).Genomics 3129–136.
Gardiner, K., Horisberger, M., Kraus, J., Tantravahi, U., Korenberg, J., Rao, V., Reddy, S., and Patterson, D. (1990).EMBO J. 925–34.
Pericak-Vance, M.A., Yamaoka, L.H., Haynes, C.S., Speer, M.C., Haines, J.L., Gaskell, P.C., Hung, W.Y., Clark, C.M., Heyman, A.L., Trofatter, J.A., Eisenmenger, J.P., Gilbert, J.R., Lee, J.E., Alberts, M.J., Dawson, D.V., Bartlett, R.J., Earl, N.L., Siddique, T., Vance, J.M., Conneally, P.M., and Roses, A.D. (1988).Exp. Neurol. 102271–279.
Schellenberg, G.D., Bird, T.D., Wijsman, E.M., Moore, D.K., Boehnke, M., Bryant, E.M., Lampe, T.H., Nochlin, D., Sumi, S.M., Deeb, S.S., Beyreuther, K., and Martin, G.M. (1988).Science 2411507–1510.
Farrer, L.A., Myers, R.H., Cupples, L.A., St George-Hyslop, P.H., Bird, T.D., Rossor, M.N., Mullan, M.J., Polinsky, R., Nee, L., Heston, L., Van Broeckhoven, C., Martin, J-J., Crapper-McLachlan, D., and Growdon, J.H. (1990).Neurology 40395–403.
St. George-Hyslop, P., Haines, J., Farrar, L., et al. (1988). InCurrent Communications in Molecular Biology. (eds.) Davies, P., Finch, C. (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York) pp. 159–168.
Carrit, B., and Litt, M. (1989).Cytogenet. Cell Genet. 51358–371.
Van Camp, G., Stinissen, P., Van Hul, W., Backhovens, H., Wehnert, A., Vandenberghe, A., and Van Broeckhoven, C. (1989).Hum. Genet 8358–60.
Raziuddin, A., Sarkar, F.H., Dutkowski, R., Shulman, L., Ruddle, F.H., and Gupta, S.L. (1984).Proc. Natl. Acad. Sci. U.S.A. 815504–5508.
Cox, D.R., and Epstein, C.J. (1985).Ann. N.Y. Acad. Sci. 450169–177.
Van Keuren, M.L., Stewart, G.D., Bradley, C.M., Kurnit, D.M., Neve, R.L., Watkins, P.C., Tanzi, R.E., Gusella, J.F., and Patterson, D. (1989).Am. J. Med. Genet. 33369–375.
Neve, R.L., Stewart, G.D., Newcomb, P., Van Keuren, M.L., Patterson, D., Drabkin, D.M., and Kurnit, D.M. (1986).Gene 49361–369.
Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982).Molecular Cloning, A Laboratory Manual, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York).
Raeymaekers, P., Van Broeckhoven, C., Backhovens, H., Wehnert, A., Muylle, L., De Jonghe, P., Gheuens, J., and Vandenberghe, A. (1988).Hum. Genet. 7876–78.
Church, G.M., and Gilbert, W. (1984).Proc. Natl. Acad. Sci. U.S.A. 811991–1995.
Burmeister, M., and Lehrach, H. (1989).Trends Genet. 5(2):41.
No crosshybridization was observed between the fVC phage clones and the following chromosome 21 probes: pGSM21, pGSE9, pPW511, pPW233F, pPW228C, pPW236B, G95a, G95b, G95c, JG90, pPW235D, 4U, pPW267C, 21.3, 26c, pPW245D, SF85, SF105, IFNAR, IFNBR. All probes tested are localized in 21q21.2-pter and have been described elsewhere (17).
Deininger, P., Jolly, D.J., Rubin, C.M., Friedmann, T., and Schmid, C.W. (1981).J. Mol. Biol. 15117–33.
Miyake, T., Migita, K., and Sakaki, Y. (1983).Nucleic Acids Res. 116837–6846.
Dams, E., Hendriks, L., Van de Peer, Y., Neefs, J., Smits, G., Vandenbempt, I., and De Wachter, R. (1988).Nucleic Acids Res. 16(suppl.):r87-r173.
Devilee, P., Cremer, T., Slagboom, P., Bakker, E., Scholl, H.P., Hager, H.D., Stevenson, A.F.G., Cornelisse, C.J., and Pearson, P.L. (1986).Cytogenet. Cell Genet. 41193–201.
Kurnit, D.M., Roy, S., Stewart, G.D., Schwedock, J., Neve, R.L., Bruns, G.A.P., Van Keuren, M.L., and Patterson, D. (1986).Cytogenet. Cell Genet. 43109–116.
Waye, J.S., and Huntington, H.F. (1989).Proc. Natl. Acad. Sci. U.S.A. 866250–6254.
Doering, J.L., Burket, A.E., and Carnahan, S.L. (1988).FEBS Lett. 231130–134.
Van Camp, G., Stinissen, P., Vandenberghe, A., and Van Broeckhoven, C. (1989).Nucleic Acids Res. 174420.
Tantravahi, U., Stewart, G.D., Van Keuren, M., McNeil, G., Roy, S., Patterson, D., Drabkin, H., Lalande, M., Kurnitt, D.M., and Latt, S.A. (1988).Hum. Genet. 79196–202.
Fuscoe, J.C., Collins, C.C., Pinkel, D., and Gray, J.W. (1989).Genomics 5100–109.
Arheim, N., Krystal, M., Schmickel, R., Wilson, G., Ryder, O., and Zimmer, E. (1980).Proc. Natl. Acad. Sci. U.S.A. 777323–7327.
Danciger, E., Dafni, N., Bernstein, Y., Laver-Rudich, Z., Neer, A., and Groner, Y. (1986).Proc. Natl. Acad. Sci. U.S.A. 833619–3623.
Hawkins, J.W., Van Keuren, M.L., Piatigorsky, J., Law, M.L., Patterson, D., and Kao, F.T. (1987).Hum. Genet. 76375–380.
Sacchi, N., Watson, D.K., Guerts Van Kessel, H.M., Hagemeijer, A., Kersey, J., Drabkin, H.D., Patterson, D., and Papas, T.S. (1986).Science 231379–382.
Van Camp, G., Stinissen, P., Van Hul, W., Wehnert, A., Backhovens, H., Vandenberghe, A., and Van Broeckhoven, C. (1989).Cytogenet. Cell Genet. 511095–1096.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Van Camp, G., Van Hul, W., Backhovens, H. et al. Physical mapping of chromosome 21 DNA markers in Alzheimer's disease region using somatic cell hybrids. Somat Cell Mol Genet 16, 241–249 (1990). https://doi.org/10.1007/BF01233360
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01233360