Summary
A recombinant DNA sequence, λRB6, was isolated from a human X chromosome library and shown to be X-specific by hybridisation to DNA from a human-mouse somatic cell hybrid containing X as the only human chromosome. The cloned sequence was located on the long arm distal to Xq13 using a human-mouse somatic cell hybrid containing a partial human X chromosome. DNA samples isolated from control human females were digested with the restriction enzyme MspI, and analysed by “blotting” and hybridisation to the radioactive cloned DNA. Eight of 14 individuals from a random population showed a single hybridising band 7.5 kilobase pairs (kb) in length, but six showed an additional band 10.1 kb in length. DNA from 12 members of a family with X-linked thyroxine-binding globulin deficiency was analysed for the segregation of this polymorphism. The results show that the polymorphism is inherited in a Mendelian fashion, and that the disease locus is not closely linked to the polymorphic site. Such polymorphisms will be useful as markers for chromosome mapping and for the antenatal diagnosis of genetic diseases.
Similar content being viewed by others
References
Bell, GI, Karam RW, Rutter WJ (1981) Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc Natl Acad Sci USA 78:5759–5763
Botstein D, White RL, Skolnick M, Davies RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331
Crampton JM, Davies KE, Knapp TF (1981) The occurrence of families of repetitive sequences in a library of cloned cDNA from human lymphocytes. Nucleic Acids Res 9:3821–3833
Davies KE (1981) The application of DNA recombinant technology to the analysis of the human genome and genetic disease. Hum Genet 58:351–357
Davies KE, Young BD, Elles RG, Hill MEE, Williamson R (1981) Cloning of a representative genomic libarary of the human X chromosome after sorting by flow cytometry. Nature 293:374–376
Goodfellow P, Banting G, Levy R, Povey S, McMichael A (1980) A human X-linked antigen defined by a monoclonal antibody. Somatic Cell Genet 6:777–787
Goodfellow P, Banting G, Chambers S, Trousdale J, Solomon E (1982) Introduction of a human X-6 translocation chromosome into a mouse teratocarcinoma; Investigation of control of HLA-ABC expression. Proc Natl Acad Sci USA 79:1190–1194
Gusella JF, Keys C, Varsanyi-Breitner A, Kao FT, Jones C, Puck TT, Houseman D (1980) Isolation and localization of DNA segments from specific human chromosomes. Proc Natl Acad Sci USA 77:2829–2833
Jeffreys AJ (1979) DNA sequence variants in the Gγ-, Aγ- δ- and β-globin genes of man. Cell 18:1–10
Jeffreys AF, Flavell RA (1977) The rabbit β-globin gene contains a large insert in the coding sequence. Cell 12:1097–1108
Kan YW, Dozy AM (1980) Polymorphism of DNA sequence adjacent to the human β-globin structural gene: Relationship to sickle mutation. Proc Natl Acad Sci USA 75:5631–5635
Kan YW, Lee KY, Furbetta M, Angius A, Cao A (1980) Polymorphism of DNA sequence in the β-globin gene region. N Engl J Med 302:185–188
Little PFR, Annison G, Darling S, Williamson R, Camba I, Modell B (1980) Model for antenatal diagnosis of β-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphisms. Nature 285:144–1147
McKusick VA, Ruddle FH (1977) The status of the gene map of the human chromosomes. Science 196:390–405
Morton NE (1959) Genetic tests under incomplete ascertainment. Am J Hum Genet 11:1–16
Phillips JA, Penny SR, Kazazian HH, Boehm CD, Scott AF, Smith KD (1980) Prenatal diagnosis of sickle cell anaemia by restriction endonuclease analysis: HindIII polymorphisms in β-globin genes extend test applicability. Proc Natl Acad Sci USA 77:2853–2856
Renwick JH (1969) Progress in mapping human autosomes. Br Med Bull 25:65–67
Rigby PWJ, Dieckmann M, Rhodes C, Berg P (1977) Labeling DNA to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol 113:237–254
Solomon E, Bodmer WF (1979) Evolution of sickle variant gene. Lancet i:923
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Thomas P (1980) Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci USA 77:5201–5205
Wolf SF, Mareni CE, Migeon BR (1980) Isolation and characterization of cloned DNA sequences that hybridize to the human X chromosome. Cell 21:95–102
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hill, M.E.E., Davies, K.E., Harper, P. et al. The mendelian inheritance of a human X chromosome-specific DNA sequence polymorphism and its use in linkage studies of genetic disease. Hum Genet 60, 222–226 (1982). https://doi.org/10.1007/BF00303007
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00303007