Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene

  • 52 Accesses

  • 2 Citations


Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. A minimum recombinant analysis using D13S22, ESD, RB1, D13S31, D13S55, D13S26, D13S39, and D13S12, all localized at 13q14-q22, has been carried out in 20WD families of Northwest-European origin. No inconsistencies have been observed with respect to locus order or location of the WD locus (WND) compared with previous linkage studies. D13S31 was mapped as the closest marker proximal to WND, whereas D13S55 and D13S26 were mapped as the closest markers distal to WND. We have identified a crossover between WND and D13S31 in one family and a crossover between WND and D13S55 in another. These crossover sites can be used as reference points for new chromosome 13q14-q21 markers, and are therefore important for a more accurate mapping of the WD locus.

This is a preview of subscription content, log in to check access.


  1. Bowcock AM, Farrer LA, Cavalli-Sforza LL, Hebert JM, Kidd KK, Frydman M, Bonne-Tamir B (1987) Mapping the Wilson disease locus to a cluster of linked polymorphic markers on chromosome 13. Am J Hum Genet 41:27–35

  2. Bowcock AM, Farrer LA, Hebert JM, Agger M, Sternlieb I, Scheinberg IH, Buys CHCM, Scheffer H, Frydman M, Chajek-Saul T, Bonne-Tamir T, Cavalli-Sforza LL (1988) Eight closely linked loci place the Wilson disease locus within 13q14-q21. Am J Hum Genet 43:664–674

  3. Bowcock AM, Farrer LA, Hebert JM, Agger M, Bale AE, Buys CHCM, James D, Donis-Keller H, Cavalli-Sforza LL (1989) A fine structure linkage map for chromosome 13. (10th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 51:966–967

  4. Bowcock AM, Farrer LA, Hebert JM, Bale AE, Cavalli-Sforza LL (1991) A contiguous linkage map of chromosome 13q (abstract), (11th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 58:1982–1983

  5. Cox DW, Fraser FC, Sass-Kortsak A (1972) A genetic study of Wilson's disease: evidence for heterogeneity. Am J Hum Genet 24:646–666

  6. Danks DM (1989) Disorders of copper transport. In: Stanbury JB (ed) Metabolic basis of inherited disease. McGraw-Hill, New York, pp 1411–1421

  7. Farrer LA, Bowcock AM, Hebert JM, Bonne-Tamir B, Agger M, Sternlieb I, St George-Hyslop P, Loessner J, Bale AE, DonisKeller H, Frydman M, Scheinberg IH, Cavalli-Sforza LL (1989) Identification of two closely linked and flanking markers to the Wilson's disease locus. (10th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 51:997–998

  8. Farrer LA, Bowcock AM, Hebert JM, Bonne-Tamir B, Sternlieb I, Giagheddu M, St. George-Hyslop P, Frydman M, Loessner J, Demelia L, Carcassi C, Lee R, Beker R, Bale AE, Donis-Keller H, Scheinberg IH, Cavalli-Sforza LL (1991) Predictive testing for Wilson's disease using tightly linked and flanking DNA markers. Neurology 41:992–999

  9. Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13

  10. Figus A, Lampis R, Devoto M, Ristaldi MS, Ideo A, De Virgilis S, Nurchi AM, Corrias A, Corda R, Lai ME, Tocco A, Depiano A, Solinas A, Zancan L, Lee WH, Cao A, Pirastu M, Balestrieri A (1989) Carrier detection and early diagnosis of Wilson's disease by restriction fragment length polymorphism analysis. J Med Genet 26:78–82

  11. Houwen RHJ, Scheffer H, Te Meerman GJ, Van der Vlies PJ, Buys CHCM (1990) Close linkage of Wilson disease locus (WND) to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14. Hum Genet 85:560–562

  12. Kidd KK, Bowcock AM, Smidtke J, Track RK, Ricciuti F, Hutchings G, Bale A, Pearson P, Willard HF (1989) Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet 51:622–947

  13. Rommens JM, Iannuzi MC, Kerem B-S, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Tsui L-S, Collins FS (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245:1059–1065

  14. Scheffer H, Penninga D, Goor N, Pearson PL, Buys CHCM (1986) A four-allele RFLP identified by an anonymous single copy clone at 13q21–13qter (HGM8 assignment no. D13S12). Nucleic Acids Res 14:3148

  15. Scheffer H, Te Meerman GJ, Kruize YCM, Van den Berg JHM, Penninga DP, Tan KEWP, Der Kinderen DJ, Buys CHCM (1989) Linkage analysis of families with hereditary retinoblastoma: nonpenetrance of mutation revealed by combined use of markers within and flanking the RB1-gene. Am J Hum Genet 45:252–260

  16. Scheinberg IH, Sternlieb I (1984) Wilson's disease. Saunders, Philadelphia

  17. Sternlieb I, Scheinberg IH (1968) Prevention of Wilson's disease in asymptomatic patients. N Engl J Med 278:352–359

  18. Te Meerman GJ (1991) A logic programming approach to pedigree analysis. Thesis, University of Groningen

  19. Thompson EA (1987) Crossover counts and likelihood in multipoint linkage analysis. IMA J Math Appl Med Biol 4:93–108

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Scheffer, H., Houwen, R.H.J., TeMeerman, G.J. et al. Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene. Hum Genet 89, 607–611 (1992). https://doi.org/10.1007/BF00221947

Download citation


  • Copper
  • Internal Medicine
  • Metabolic Disease
  • Reference Point
  • Genetic Localization