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. 1990 Oct;87(20):8056–8059. doi: 10.1073/pnas.87.20.8056

Diastrophic dysplasia gene maps to the distal long arm of chromosome 5.

J Hästbacka 1, I Kaitila 1, P Sistonen 1, A de la Chapelle 1
PMCID: PMC54891  PMID: 1978318

Abstract

We have used polymorphic DNA markers to map the gene for a clinically well-characterized form of osteochondrodysplasia, diastrophic dysplasia (DD), an autosomal recessive disorder of unknown pathogenesis. Linkage was analyzed in 13 families with two or three affected sibs comprising a total of 84 individuals. Positive two-point logarithm-of-odds (lod) scores were obtained between the DD locus and three polymorphic markers on chromosome 5. The highest pairwise lod score estimate of 7.37 with zero recombination to locus D5S72 suggests very tight linkage. There was no evidence of heterogeneity. Multipoint linkage analysis against the published order of the three loci gave the result centromere-D5S84-(DD, D5S72)-D5S61-terminus with a four-point lod score of 9.11. The present findings place the DD locus distal to the gene for adenomatous polyposis coli on the distal part of the long arm of chromosome 5. Our results provide a basis for refining the map position of the DD locus followed by physical localization, isolation, and characterization of the gene.

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Selected References

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  1. Anderson M. A., Gusella J. F. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984 Nov;20(11):856–858. doi: 10.1007/BF02619631. [DOI] [PubMed] [Google Scholar]
  2. Bodmer W. F., Bailey C. J., Bodmer J., Bussey H. J., Ellis A., Gorman P., Lucibello F. C., Murday V. A., Rider S. H., Scambler P. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987 Aug 13;328(6131):614–616. doi: 10.1038/328614a0. [DOI] [PubMed] [Google Scholar]
  3. Byers P. H. Inherited disorders of collagen gene structure and expression. Am J Med Genet. 1989 Sep;34(1):72–80. doi: 10.1002/ajmg.1320340114. [DOI] [PubMed] [Google Scholar]
  4. Byers P. H. Molecular heterogeneity in chondrodysplasias. Am J Hum Genet. 1989 Jul;45(1):1–4. [PMC free article] [PubMed] [Google Scholar]
  5. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  6. Elima K., Kaitila I., Mikonoja L., Elonsalo U., Peltonen L., Vuorio E. Exclusion of the COL2A1 gene as the mutation site in diastrophic dysplasia. J Med Genet. 1989 May;26(5):314–319. doi: 10.1136/jmg.26.5.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Erickson R. P. Mapping dysmorphic syndromes with the aid of the human/mouse homology map. Am J Hum Genet. 1990 Jun;46(6):1013–1016. [PMC free article] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  9. Francomano C. A., Liberfarb R. M., Hirose T., Maumenee I. H., Streeten E. A., Meyers D. A., Pyeritz R. E. The Stickler syndrome: evidence for close linkage to the structural gene for type II collagen. Genomics. 1987 Dec;1(4):293–296. doi: 10.1016/0888-7543(87)90027-9. [DOI] [PubMed] [Google Scholar]
  10. Horton W. A., Campbell D., Machado M. A., Chou J. Type II collagen screening in the human chondrodysplasias. Am J Med Genet. 1989 Dec;34(4):579–583. doi: 10.1002/ajmg.1320340425. [DOI] [PubMed] [Google Scholar]
  11. Horton W. A., Rimoin D. L., Lachman R. S., Skovby F., Hollister D. W., Spranger J., Scott C. I., Hall J. G. The phenotypic variability of diastrophic dysplasia. J Pediatr. 1978 Oct;93(4):609–613. doi: 10.1016/s0022-3476(78)80896-8. [DOI] [PubMed] [Google Scholar]
  12. Kidd K. K., Bowcock A. M., Schmidtke J., Track R. K., Ricciuti F., Hutchings G., Bale A., Pearson P., Willard H. F., Gelernter J. Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet. 1989;51(1-4):622–947. doi: 10.1159/000132810. [DOI] [PubMed] [Google Scholar]
  13. LAMY M., MAROTEAUX P. [Diastrophic nanism]. Presse Med. 1960 Nov 23;68:1977–1980. [PubMed] [Google Scholar]
  14. Lander E. S., Botstein D. Mapping complex genetic traits in humans: new methods using a complete RFLP linkage map. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):49–62. doi: 10.1101/sqb.1986.051.01.007. [DOI] [PubMed] [Google Scholar]
  15. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lee B., Vissing H., Ramirez F., Rogers D., Rimoin D. Identification of the molecular defect in a family with spondyloepiphyseal dysplasia. Science. 1989 May 26;244(4907):978–980. doi: 10.1126/science.2543071. [DOI] [PubMed] [Google Scholar]
  17. Nakamura Y., Lathrop M., Leppert M., Dobbs M., Wasmuth J., Wolff E., Carlson M., Fujimoto E., Krapcho K., Sears T. Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet. 1988 Nov;43(5):638–644. [PMC free article] [PubMed] [Google Scholar]
  18. Norio R., Nevanlinna H. R., Perheentupa J. Hereditary diseases in Finland; rare flora in rare soul. Ann Clin Res. 1973 Jun;5(3):109–141. [PubMed] [Google Scholar]
  19. Rimoin D. L. The chondrodystrophies. Adv Hum Genet. 1975;5:1–118. doi: 10.1007/978-1-4615-9068-2_1. [DOI] [PubMed] [Google Scholar]
  20. Scheck M., Parker J., Daentl D. Hyaline cartilage changes in diastrophic dwarfism. Virchows Arch A Pathol Anat Histol. 1978 Jul 26;378(4):347–359. doi: 10.1007/BF00465601. [DOI] [PubMed] [Google Scholar]
  21. Stanescu V., Stanescu R., Maroteaux P. Pathogenic mechanisms in osteochondrodysplasias. J Bone Joint Surg Am. 1984 Jul;66(6):817–836. doi: 10.2106/00004623-198466060-00002. [DOI] [PubMed] [Google Scholar]
  22. Tiller G. E., Rimoin D. L., Murray L. W., Cohn D. H. Tandem duplication within a type II collagen gene (COL2A1) exon in an individual with spondyloepiphyseal dysplasia. Proc Natl Acad Sci U S A. 1990 May;87(10):3889–3893. doi: 10.1073/pnas.87.10.3889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Walker B. A., Scott C. I., Hall J. G., Murdoch J. L., McKusick V. A. Diastrophic dwarfism. Medicine (Baltimore) 1972 Jan;51(1):41–59. doi: 10.1097/00005792-197201000-00003. [DOI] [PubMed] [Google Scholar]
  24. Wasmuth J. J., Park C., Ferrell R. E. Report of the committee on the genetic constitution of chromosome 5. Cytogenet Cell Genet. 1989;51(1-4):137–148. doi: 10.1159/000132789. [DOI] [PubMed] [Google Scholar]
  25. Wordsworth P., Ogilvie D., Priestley L., Smith R., Wynne-Davies R., Sykes B. Structural and segregation analysis of the type II collagen gene (COL2A1) in some heritable chondrodysplasias. J Med Genet. 1988 Aug;25(8):521–527. doi: 10.1136/jmg.25.8.521. [DOI] [PMC free article] [PubMed] [Google Scholar]

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