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The gene for achondroplasia maps to the telomeric region of chromosome 4p

Nature Genetics volume 6, pages 314–317 (1994)Cite this article

Abstract

Achondroplasia is the most common type of genetic dwarfism. It is characterized by disproportionate short stature and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. We have now mapped the achondroplasia gene near the telomere of the short arm of chromosome 4 (4p16.3), by family linkage studies using 14 pedigrees. A positive lod score of z=3.35 with no recombinants was obtained with an intragenic marker for IDUA. This localization will facilitate the positional cloning of the disease gene.

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References

  1. Scott, Jr., C. Dwarfism. CIBA-GEIGY Clinical Symposia 40, 3–7 (1988).

    Google Scholar 

  2. Hecht, J., Francomano, C., Horton, W. & Annegers, J. Mortality in achondroplasia. Am. J. hum. Genet. 41, 454–464 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Pauli, R. et al. Homozygous achondroplasia with survival beyond infancy. Am. J. med. Genet. 16, 459–473 (1983).

    Article  CAS  PubMed  Google Scholar 

  4. Orioli, I., Castilla, E. & Barbosa-Neto, J. The birth prevalence rates for skeletal dysplasias. J. med. Genet. 23, 328–332 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Stanescu, R., Stanescu, V. & Maroteaux, P. Homozygous achondroplasia: morphologic and biochemical study of cartilage. Am. J. med. Genet. 37, 412–421 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Pedrini-Mille, A. & Pedrini, V. Proteoglycans and glycosaminoglycans of human achondroplastic cartilage. J. Bone Joint Surg. 64-A, 39–46 (1982).

    Article  Google Scholar 

  7. Finkelstein, J. et al. Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia. Am. J. hum. Genet. 48, 97–102 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Ogilvie, D., Wordsworth, P., Thompson, E. & Sykes, B. Evidence against the structural gene encoding type II collagen (COL2A1) as the mutant locus in achondroplasia. J. med. Genet. 23, 19–22 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Francomano, C. & Pyeritz, R. Achondroplasia is not caused by mutation in the gene for type II collagen. Am. J. med. Genet. 29, 955–961 (1988).

    Article  CAS  PubMed  Google Scholar 

  10. Sweetman, W. et al. SSCP and segregation analysis of the human type X collagen gens (COL10A1) in heritable forms of chondrodysplasia. Am. J. hum. Genet. 51, 841–849 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Weiasenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).

    Article  Google Scholar 

  12. Scott, H. et al. An 86-bp VNTR within IDUA is the basis of the D4S111 polymorphic locus. Genomics 14, 1118–1120 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Scott, H. et al. Chromosomal localization of the human α-L-lduronidase gene (IDUA) to 4p 16.3. Am. J. hum. Genet. 47, 802–807 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Magenis, R. et al. Huntington disease-linked restriction fragment length polymorphism localized within band p16.1 of chromosome 4 by in situ hybridization. Am. J. hum. Genet. 39, 383–391 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang, H. et al. Subregional assignment of the linked marker G8 (D4S1O) for Huntington disease to chromosome 4p16.1–16.3. Am. J. hum. Genet. 39, 393–396 (1986).

    Google Scholar 

  16. Scott, H. et al. Identification of mutations in the a-L-Iduronidase gene (IDUA) that causes Hurier and Scheie syndromes. Am. J. hum. Genet. 53, 973–986 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Cordone, M. et al. Ultrasonographlc features in a case of heterozygous achondroplasia at 25 weeks gestation. Pren. Diagnosis 13, 395–401 (1993).

    Article  CAS  Google Scholar 

  18. McKusick, V.A., Kelly, T.E. & Dorst, J.P. Observations suggesting allelism of the achondroplasia and hypochondroplasia genes. J. med. Genet. 10, 11–16 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schinzel, A. Catalogue of unbalanced chromosome aberrations in man. 161–164 (Walter de Gruyter, Berlin, 1984).

    Google Scholar 

  20. Gandelman, K-Y., Gibson, L., Meyn, M. & Yang-Feng, T.L. Molecular definition of the smallest region of deletion overlap in the Wolf–Hirschhom syndrome. Am. J. hum. Genet. 51, 571–578 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lin, C. et al. New DNA markers in the Huntington's disease gene candidate region. Som. Cell molec. Genet. 17, 481–488 (1991).

    Article  CAS  Google Scholar 

  22. Weber, B. et al. Isolation and characterization of new highly polymorphic DNA markers from the Huntington disease region. Am. J. hum. Genet. 47, 382–393 (1992).

    Google Scholar 

  23. Tommerup, N. et al. A Zinc-finger gene ZNF141 mapping at 4p16.3/D4S90 is a candidate gene for the Wolf-Hirschhom (4p-) syndrome. Hum. molec. Genet. 2, 1571–1576 (1993).

    Article  CAS  PubMed  Google Scholar 

  24. Taylor, S. et al. Cloning of the a-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification. Nature Genet. 2, 223–227 (1992).

    Article  CAS  PubMed  Google Scholar 

  25. Ambrose, C. et al. A novel G protein-coupled receptor kinase gene cloned from 4p16.3. Hum. molec. Genet. 1, 697–703 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Duyao, M. et al. A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins. Hum. molec. Genet. 2, 673–676 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Collins, C., Schappert, K. & Hayden, M. The genomic organization of a novel regulatory myosin light chain gene (MYL5) that maps to chromosome 4p16.3 and shows different patterns of exxpression between primates. Hum. molec. Genet. 1, 727–733 (1992).

    CAS  PubMed  Google Scholar 

  28. Weber, B. et al. Genomic organization and complete sequence of the human gene encoding the β-subunit of the cGMP phosphodiesterase and its localization to 4p16.3. Nucl. Acids Res. 19, 6263–6268 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Padanilam, B. et al. Characterization of the human HOX7 cDNA and identification of polymorphic markers. Hum. molec. Genet. 1, 407–410 (1992).

    Article  CAS  PubMed  Google Scholar 

  30. Stadler, H. et al. Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4. Proc. natn. Acad. Sci. U.S.A. 89, 11579–11583 (1992).

    Article  CAS  Google Scholar 

  31. Thompson, L. et al. A gene encoding a flbroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4. Genomics 11, 1133–1142 (1991).

    Article  CAS  PubMed  Google Scholar 

  32. Peters, K., Ornitz, D., Werner, S. & Williams, L. Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev. Biol. 155, 423–430 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Langer, Jr., L., Schaefer, B. & Wadswoith, D. Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type. Am. J. med. Genet. 47, 772–781 (1993).

    Article  PubMed  Google Scholar 

  34. Vignal, A. et al. Nonradioactive multiplex procedure for genotyping of microsatellite markers. Meth. molec. Genet. 1, 211–221 (1993).

    CAS  Google Scholar 

  35. Alitto, B. et al. Assay by polymerase chain reaction (PCR) of multi-allele polymorphisms in the Huntington's disease region of chromosome 4. Molec. cell. Probes 6, 513–520 (1992).

    Article  Google Scholar 

  36. Taylor, S., Barnes, G., MacDonald, M. & Gusella, J. A dinucleotide repeat polymorphism at the D4S127 locus. Hum. molec. Genet. 1, 142 (1992).

    Article  CAS  PubMed  Google Scholar 

  37. Lathrop, G., Lalouel, J., Julier, C. & Ott, J. Strategies for multi-point linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

    Article  CAS  Google Scholar 

  38. Locke, P. et al. A genetic linkage map of the chromosome 4 short arm. Som. Cell molec. Genet. 19, 95–101 (1993).

    Article  CAS  Google Scholar 

  39. Murray, J. et al. Cooperative Human Linkage Center Report 1 (1) 1993.

    Google Scholar 

  40. Lander, E. & Green, P. Construction of multi-locus genetic linkage maps in humans. Proc. natn. Acad. Sci. U.S.A. 85, 2363–2367 (1987).

    Article  Google Scholar 

  41. MacDonald, M. et al. Huntington disease-linked locus D4S111 exposed as the α-L-lduronidase gene. Som. Cell molec. Genet. 17, 421–425 (1991).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticutt, 06030, USA

    Milen Velinov, Ivaylo Stoilov & Petros Tsipouras

  2. Molecular Neurogenetics Unit, Massachusetts General Hospital and Department of Genetics,

    Susan A. Slaugenhaupt & James F. Gusella

  3. Harvard Medical School, Boston, Massachusetts, 02129, USA

    Susan A. Slaugenhaupt & James F. Gusella

  4. Division of Medical Genetics, Alfred I. duPont Institute, Wilmington, Delaware, 19899, USA

    Charles I. Scott Jr.

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  1. Milen Velinov
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  4. Charles I. Scott Jr.
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  5. James F. Gusella
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Velinov, M., Slaugenhaupt, S., Stoilov, I. et al. The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nat Genet 6, 314–317 (1994). https://doi.org/10.1038/ng0394-314

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