Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly
| Autor: | Herma C. van der Linde, Simon J. H. Heaney, Ei-ichi Takahashi, Marijke J. van Baren, Mikio Suzuki, Sumihare Noji, Stephen W. Scherer, Dai Ayusawa, Yutaka Nakahori, Nurten A. Akarsu, Toshikatsu Shinka, Ben A. Oostra, Kazuhiko Nakabayashi, Peter Heutink, Taizo Horikoshi, Robert E. Hill, Guido J. Breedveld, Minoru Shibata, Laura A. Lettice, Naoto Endo, Marijke Joosse |
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| Přispěvatelé: | Clinical Genetics, Cell biology |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Heterozygote
Triphalangeal thumb Transgene Mutant Restriction Mapping Regulator Translocation Breakpoint Biology medicine.disease_cause Translocation Genetic Mice medicine Animals Humans Hedgehog Proteins Cloning Molecular Crosses Genetic In Situ Hybridization Fluorescence Genetics Recombination Genetic Mutation Multidisciplinary Polydactyly Preaxial polydactyly Membrane Proteins Biological Sciences medicine.disease Introns Phenotype Trans-Activators |
| Zdroj: | Proceedings of the National Academy of Sciences of the U.S.A., 99, 7548-7553. National Academy of Sciences |
| ISSN: | 0027-8424 |
| Popis: | Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch ( Ssq ). The genetic lesions in both lie within the same respective intron of the LMBR1 / Lmbr1 gene, which resides ≈1 Mb away from Shh . Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh . This regulator is most likely the target for generating PPD mutations in human. |
| Databáze: | OpenAIRE |
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