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. 1985 Aug;22(4):243–249. doi: 10.1136/jmg.22.4.243

Molecular genetics of the human X chromosome.

K E Davies
PMCID: PMC1049443  PMID: 2995673

Abstract

The human X chromosome will soon be mapped at 10 cM intervals. This will permit the localisation of any X linked disorder provided that informative families are available for linkage analysis. The location of RFLPs currently in use for clinical diagnosis is summarised. The next decade should witness the elucidation of the molecular basis of some of the more common defects, such as the muscular dystrophies and X linked mental retardation.

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Selected References

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  1. Adam A., Ziprkowski L., Feinstein A., Sanger R., Tippett P., Gavin J., Race R. R. Linkage relations of X-borne ichthyosis to the Xg blood groups and to other markers of the X in Israelis. Ann Hum Genet. 1969 May;32(4):323–332. doi: 10.1111/j.1469-1809.1969.tb00082.x. [DOI] [PubMed] [Google Scholar]
  2. Anderson W. F. Prospects for human gene therapy. Science. 1984 Oct 26;226(4673):401–409. doi: 10.1126/science.6093246. [DOI] [PubMed] [Google Scholar]
  3. Bhattacharya S. S., Wright A. F., Clayton J. F., Price W. H., Phillips C. I., McKeown C. M., Jay M., Bird A. C., Pearson P. L., Southern E. M. Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28. Nature. 1984 May 17;309(5965):253–255. doi: 10.1038/309253a0. [DOI] [PubMed] [Google Scholar]
  4. Brennand J., Chinault A. C., Konecki D. S., Melton D. W., Caskey C. T. Cloned cDNA sequences of the hypoxanthine/guanine phosphoribosyltransferase gene from a mouse neuroblastoma cell line found to have amplified genomic sequences. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1950–1954. doi: 10.1073/pnas.79.6.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Camerino G., Grzeschik K. H., Jaye M., De La Salle H., Tolstoshev P., Lecocq J. P., Heilig R., Mandel J. L. Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). Proc Natl Acad Sci U S A. 1984 Jan;81(2):498–502. doi: 10.1073/pnas.81.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Camerino G., Mattei M. G., Mattei J. F., Jaye M., Mandel J. L. Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male. Nature. 1983 Dec 15;306(5944):701–704. doi: 10.1038/306701a0. [DOI] [PubMed] [Google Scholar]
  7. Chandley A. C., Goetz P., Hargreave T. B., Joseph A. M., Speed R. M. On the nature and extent of XY pairing at meiotic prophase in man. Cytogenet Cell Genet. 1984;38(4):241–247. doi: 10.1159/000132070. [DOI] [PubMed] [Google Scholar]
  8. Choo K. H., George D., Filby G., Halliday J. L., Leversha M., Webb G., Danks D. M. Linkage analysis of X-linked mental retardation with and without fragile-X using factor IX gene probe. Lancet. 1984 Aug 11;2(8398):349–349. doi: 10.1016/s0140-6736(84)92715-6. [DOI] [PubMed] [Google Scholar]
  9. Choo K. H., Gould K. G., Rees D. J., Brownlee G. G. Molecular cloning of the gene for human anti-haemophilic factor IX. Nature. 1982 Sep 9;299(5879):178–180. doi: 10.1038/299178a0. [DOI] [PubMed] [Google Scholar]
  10. Clayton J., Emery A. DNA probes in Duchenne muscular dystrophy. Lancet. 1984 Nov 17;2(8412):1151–1152. doi: 10.1016/s0140-6736(84)91578-2. [DOI] [PubMed] [Google Scholar]
  11. Cooke H. J., Brown W. A., Rappold G. A. Closely related sequences on human X and Y chromosomes outside the pairing region. Nature. 1984 Sep 20;311(5983):259–261. doi: 10.1038/311259a0. [DOI] [PubMed] [Google Scholar]
  12. Daffos F., Forestier F., Grangeot-Keros L., Capella Pavlovsky M., Lebon P., Chartier M., Pillot J. Prenatal diagnosis of congenital rubella. Lancet. 1984 Jul 7;2(8393):1–3. doi: 10.1016/s0140-6736(84)91993-7. [DOI] [PubMed] [Google Scholar]
  13. Davies K. E., Pearson P. L., Harper P. S., Murray J. M., O'Brien T., Sarfarazi M., Williamson R. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Res. 1983 Apr 25;11(8):2303–2312. doi: 10.1093/nar/11.8.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davies K. E., Speer A., Herrmann F., Spiegler A. W., McGlade S., Hofker M. H., Briand P., Hanke R., Schwartz M., Steinbicker V. Human X chromosome markers and Duchenne muscular dystrophy. Nucleic Acids Res. 1985 May 24;13(10):3419–3426. doi: 10.1093/nar/13.10.3419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davies K. E., Young B. D., Elles R. G., Hill M. E., Williamson R. Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry. Nature. 1981 Oct 1;293(5831):374–376. doi: 10.1038/293374a0. [DOI] [PubMed] [Google Scholar]
  16. De Arce M. A., Kearns A. The fragile X syndrome: the patients and their chromosomes. J Med Genet. 1984 Apr;21(2):84–91. doi: 10.1136/jmg.21.2.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Drayna D., Davies K., Hartley D., Mandel J. L., Camerino G., Williamson R., White R. Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. Proc Natl Acad Sci U S A. 1984 May;81(9):2836–2839. doi: 10.1073/pnas.81.9.2836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ellis K. P., Davies K. E. An appraisal of the application of recombinant DNA techniques to chromosome defects. Biochem J. 1985 Feb 15;226(1):1–11. doi: 10.1042/bj2260001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Emery A. E. Duchenne muscular dystrophy. Genetic aspects, carrier detection and antenatal diagnosis. Br Med Bull. 1980 May;36(2):117–122. doi: 10.1093/oxfordjournals.bmb.a071624. [DOI] [PubMed] [Google Scholar]
  20. Francke U., Bakay B., Connor J. D., Coldwell J. G., Nyhan W. L. Linkage relationships of X-linked enzymes glucose-6-phosphate dehydrogenase and hypoxanthine guanine phosphoribosyltransferase: recombination in female offspring of compound heterozygotes. Am J Hum Genet. 1974 Jul;26(4):512–522. [PMC free article] [PubMed] [Google Scholar]
  21. Gal A., Stolzenberger C., Wienker T., Wieacker P., Ropers H. H., Friedrich U., Bleeker-Wagemakers L., Pearson P., Warburg M. Norrie's disease: close linkage with genetic markers from the proximal short arm of the X chromosome. Clin Genet. 1985 Mar;27(3):282–283. doi: 10.1111/j.1399-0004.1985.tb00221.x. [DOI] [PubMed] [Google Scholar]
  22. Gall J. G., Pardue M. L. Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci U S A. 1969 Jun;63(2):378–383. doi: 10.1073/pnas.63.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Giannelli F., Anson D. S., Choo K. H., Rees D. J., Winship P. R., Ferrari N., Rizza C. R., Brownlee G. G. Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency). Lancet. 1984 Feb 4;1(8371):239–241. doi: 10.1016/s0140-6736(84)90122-3. [DOI] [PubMed] [Google Scholar]
  24. Goodfellow P., Banting G., Sheer D., Ropers H. H., Caine A., Ferguson-Smith M. A., Povey S., Voss R. Genetic evidence that a Y-linked gene in man is homologous to a gene on the X chromosome. Nature. 1983 Mar 24;302(5906):346–349. doi: 10.1038/302346a0. [DOI] [PubMed] [Google Scholar]
  25. Goss S. J., Harris H. Gene transfer by means of cell fusion I. Statistical mapping of the human X-chromosome by analysis of radiation-induced gene segregation. J Cell Sci. 1977 Jun;25:17–37. doi: 10.1242/jcs.25.1.17. [DOI] [PubMed] [Google Scholar]
  26. Gusella J. F., Keys C., VarsanyiBreiner A., Kao F. T., Jones C., Puck T. T., Housman D. Isolation and localization of DNA segments from specific human chromosomes. Proc Natl Acad Sci U S A. 1980 May;77(5):2829–2833. doi: 10.1073/pnas.77.5.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Harper M. E., Ullrich A., Saunders G. F. Localization of the human insulin gene to the distal end of the short arm of chromosome 11. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4458–4460. doi: 10.1073/pnas.78.7.4458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Harper P. S., O'Brien T., Murray J. M., Davies K. E., Pearson P., Williamson R. The use of linked DNA polymorphisms for genotype prediction in families with Duchenne muscular dystrophy. J Med Genet. 1983 Aug;20(4):252–254. doi: 10.1136/jmg.20.4.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hartley D. A., Davies K. E., Drayna D., White R. L., Williamson R. A cytological map of the human X chromosome--evidence for non-random recombination. Nucleic Acids Res. 1984 Jul 11;12(13):5277–5285. doi: 10.1093/nar/12.13.5277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Horwich A. L., Fenton W. A., Williams K. R., Kalousek F., Kraus J. P., Doolittle R. F., Konigsberg W., Rosenberg L. E. Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase. Science. 1984 Jun 8;224(4653):1068–1074. doi: 10.1126/science.6372096. [DOI] [PubMed] [Google Scholar]
  31. Hultén M. A., Palmer R. W., Laurie D. A. Chiasma derived genetic maps and recombination fractions: chromosome 1. Ann Hum Genet. 1982 May;46(Pt 2):167–175. doi: 10.1111/j.1469-1809.1982.tb00707.x. [DOI] [PubMed] [Google Scholar]
  32. Jolly D. J., Esty A. C., Bernard H. U., Friedmann T. Isolation of a genomic clone partially encoding human hypoxanthine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5038–5041. doi: 10.1073/pnas.79.16.5038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kan Y. W., Dozy A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5631–5635. doi: 10.1073/pnas.75.11.5631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Karlsson S., Humphries R. K., Gluzman Y., Nienhuis A. W. Transfer of genes into hematopoietic cells using recombinant DNA viruses. Proc Natl Acad Sci U S A. 1985 Jan;82(1):158–162. doi: 10.1073/pnas.82.1.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kunkel L. M., Smith K. D., Boyer S. H. Human Y-chromosome-specific reiterated DNA. Science. 1976 Mar 19;191(4232):1189–1190. doi: 10.1126/science.1257744. [DOI] [PubMed] [Google Scholar]
  37. Kunkel L. M., Tantravahi U., Kurnit D. M., Eisenhard M., Bruns G. P., Latt S. A. Identification and isolation of transcribed human X chromosome DNA sequences. Nucleic Acids Res. 1983 Nov 25;11(22):7961–7979. doi: 10.1093/nar/11.22.7961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Laurie D. A., Hultén M., Jones G. H. Chiasma frequency and distribution in a sample of human males: chromosomes 1, 2, and 9. Cytogenet Cell Genet. 1981;31(3):153–166. doi: 10.1159/000131641. [DOI] [PubMed] [Google Scholar]
  39. Lindenbaum R. H., Clarke G., Patel C., Moncrieff M., Hughes J. T. Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm. J Med Genet. 1979 Oct;16(5):389–392. doi: 10.1136/jmg.16.5.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Malcolm S., Barton P., Murphy C., Ferguson-Smith M. A. Chromosomal localization of a single copy gene by in situ hybridization--human beta globin genes on the short arm of chromosome 11. Ann Hum Genet. 1981 May;45(Pt 2):135–141. doi: 10.1111/j.1469-1809.1981.tb00315.x. [DOI] [PubMed] [Google Scholar]
  41. McKusick V. A., Ruddle F. H. The status of the gene map of the human chromosomes. Science. 1977 Apr 22;196(4288):390–405. doi: 10.1126/science.850784. [DOI] [PubMed] [Google Scholar]
  42. McKusick V. A. The Wilhelmine E. Key 1979 Invitational Lecture: The anatomy of the human genome. J Hered. 1980 Nov-Dec;71(6):370–391. doi: 10.1093/oxfordjournals.jhered.a109392. [DOI] [PubMed] [Google Scholar]
  43. Michelson A. M., Markham A. F., Orkin S. H. Isolation and DNA sequence of a full-length cDNA clone for human X chromosome-encoded phosphoglycerate kinase. Proc Natl Acad Sci U S A. 1983 Jan;80(2):472–476. doi: 10.1073/pnas.80.2.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Miller A. D., Eckner R. J., Jolly D. J., Friedmann T., Verma I. M. Expression of a retrovirus encoding human HPRT in mice. Science. 1984 Aug 10;225(4662):630–632. doi: 10.1126/science.6377498. [DOI] [PubMed] [Google Scholar]
  45. Mohandas T., Sparkes R. S., Hellkuhl B., Grzeschik K. H., Shapiro L. J. Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6759–6763. doi: 10.1073/pnas.77.11.6759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Moses M. J., Counce S. J., Paulson D. F. Synaptonemal complex complement of man in spreads of spermatocytes, with details of the sex chromosome pair. Science. 1975 Jan 31;187(4174):363–365. [PubMed] [Google Scholar]
  47. Murray J. M., Davies K. E., Harper P. S., Meredith L., Mueller C. R., Williamson R. Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature. 1982 Nov 4;300(5887):69–71. doi: 10.1038/300069a0. [DOI] [PubMed] [Google Scholar]
  48. Nussbaum R. L., Crowder W. E., Nyhan W. L., Caskey C. T. A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4035–4039. doi: 10.1073/pnas.80.13.4035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Oberle I., Camerino G., Heilig R., Grunebaum L., Cazenave J. P., Crapanzano C., Mannucci P. M., Mandel J. L. Genetic screening for hemophilia A (classic hemophilia) with a polymorphic DNA probe. N Engl J Med. 1985 Mar 14;312(11):682–686. doi: 10.1056/NEJM198503143121103. [DOI] [PubMed] [Google Scholar]
  50. Persico M. G., Toniolo D., Nobile C., D'Urso M., Luzzatto L. cDNA sequences of human glucose 6-phosphate dehydrogenase cloned in pBR322. Nature. 1981 Dec 24;294(5843):778–780. doi: 10.1038/294778a0. [DOI] [PubMed] [Google Scholar]
  51. Rappold G. A., Cremer T., Cremer C., Back W., Bogenberger J., Cooke H. J. Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes. Hum Genet. 1984;65(3):257–261. doi: 10.1007/BF00286513. [DOI] [PubMed] [Google Scholar]
  52. Sarfarazi M., Harper P. S., Kingston H. M., Murray J. M., O'Brien T., Davies K. E., Williamson R., Tippett P., Sanger R. Genetic linkage relationship between the Xg blood group system and two X chromosome DNA polymorphisms in families with Duchenne and Becker muscular dystrophy. Hum Genet. 1983;65(2):169–171. doi: 10.1007/BF00286656. [DOI] [PubMed] [Google Scholar]
  53. Schmeckpeper B. J., Smith K. D., Dorman B. P., Ruddle F. H., Talbot C. C., Jr Partial purification and characterization of DNA from the human X chromosome. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6525–6528. doi: 10.1073/pnas.76.12.6525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Singer-Sam J., Simmer R. L., Keith D. H., Shively L., Teplitz M., Itakura K., Gartler S. M., Riggs A. D. Isolation of a cDNA clone for human X-linked 3-phosphoglycerate kinase by use of a mixture of synthetic oligodeoxyribonucleotides as a detection probe. Proc Natl Acad Sci U S A. 1983 Feb;80(3):802–806. doi: 10.1073/pnas.80.3.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Siniscalco M. Approaches to human linkage. Prog Med Genet. 1979;3:221–307. [PubMed] [Google Scholar]
  56. Szabo P., Purrello M., Rocchi M., Archidiacono N., Alhadeff B., Filippi G., Toniolo D., Martini G., Luzzatto L., Siniscalco M. 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 U S A. 1984 Dec;81(24):7855–7859. doi: 10.1073/pnas.81.24.7855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Tiepolo L., Zuffardi O., Fraccaro M., di Natale D., Gargantini L., Müller C. R., Ropers H. H. Assignment by deletion mapping of the steroid sulfatase X-linked ichthyosis locus to Xp223. Hum Genet. 1980;54(2):205–206. doi: 10.1007/BF00278973. [DOI] [PubMed] [Google Scholar]
  58. Toole J. J., Knopf J. L., Wozney J. M., Sultzman L. A., Buecker J. L., Pittman D. D., Kaufman R. J., Brown E., Shoemaker C., Orr E. C. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. doi: 10.1038/312342a0. [DOI] [PubMed] [Google Scholar]
  59. Tønnesen T., Søndergaard F., Mikkelsen M., Davies K. E., Old J., Winter R. M., Hauge M. X-chromosome-specific probe DX13 for carrier detection and first trimester prenatal diagnosis in haemophilia A. Lancet. 1984 Dec 1;2(8414):1269–1270. doi: 10.1016/s0140-6736(84)92812-5. [DOI] [PubMed] [Google Scholar]
  60. Vehar G. A., Keyt B., Eaton D., Rodriguez H., O'Brien D. P., Rotblat F., Oppermann H., Keck R., Wood W. I., Harkins R. N. Structure of human factor VIII. Nature. 1984 Nov 22;312(5992):337–342. doi: 10.1038/312337a0. [DOI] [PubMed] [Google Scholar]
  61. Wieacker P., Davies K. E., Cooke H. J., Pearson P. L., Williamson R., Bhattacharya S., Zimmer J., Ropers H. H. Toward a complete linkage map of the human X chromosome: regional assignment of 16 cloned single-copy DNA sequences employing a panel of somatic cell hybrids. Am J Hum Genet. 1984 Mar;36(2):265–276. [PMC free article] [PubMed] [Google Scholar]
  62. Wieacker P., Davies K. E., Mevorah B., Ropers H. H. Linkage studies in a family with X-linked recessive ichthyosis employing a cloned DNA sequence from the distal short arm of the X chromosome. Hum Genet. 1983;63(2):113–116. doi: 10.1007/BF00291528. [DOI] [PubMed] [Google Scholar]
  63. Wieacker P., Wienker T. F., Dallapiccola B., Bender K., Davies K. E., Ropers H. H. Linkage relationships between Retinoschisis, Xg, and a cloned DNA sequence from the distal short arm of the X chromosome. Hum Genet. 1983;64(2):143–145. doi: 10.1007/BF00327111. [DOI] [PubMed] [Google Scholar]
  64. Wolff G., Müller C. R., Jobke A. Linkage of genes for chronic granulomatous disease and Xg. Hum Genet. 1980;54(2):269–271. doi: 10.1007/BF00278983. [DOI] [PubMed] [Google Scholar]
  65. Wood W. I., Capon D. J., Simonsen C. C., Eaton D. L., Gitschier J., Keyt B., Seeburg P. H., Smith D. H., Hollingshead P., Wion K. L. Expression of active human factor VIII from recombinant DNA clones. Nature. 1984 Nov 22;312(5992):330–337. doi: 10.1038/312330a0. [DOI] [PubMed] [Google Scholar]
  66. Worton R. G., Duff C., Sylvester J. E., Schmickel R. D., Willard H. F. Duchenne muscular dystrophy involving translocation of the dmd gene next to ribosomal RNA genes. Science. 1984 Jun 29;224(4656):1447–1449. doi: 10.1126/science.6729462. [DOI] [PubMed] [Google Scholar]
  67. Yang T. P., Patel P. I., Chinault A. C., Stout J. T., Jackson L. G., Hildebrand B. M., Caskey C. T. Molecular evidence for new mutation at the hprt locus in Lesch-Nyhan patients. Nature. 1984 Aug 2;310(5976):412–414. doi: 10.1038/310412a0. [DOI] [PubMed] [Google Scholar]

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