GDF6, a novel locus for a spectrum of ocular developmental anomalies
| Autor: | Curtis R. French, Karyn M. Berry, Veronica van Heyningen, Mika Asai-Coakwell, Ron Koss, Ordan J. Lehmann, Ming Ye, Martin J. Somerville, Rosemary Mueller, Andrew J. Waskiewicz |
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| Rok vydání: | 2006 |
| Předmět: |
Proband
Male Embryo Nonmammalian ved/biology.organism_classification_rank.species Non-allelic homologous recombination Biology Growth Differentiation Factor 6 Microphthalmia Article 03 medical and health sciences 0302 clinical medicine Genetics medicine Homologous chromosome Animals Humans Genetics(clinical) Colobomatous microphthalmia Genetic Predisposition to Disease Model organism Genetics (clinical) Zebrafish 030304 developmental biology Chromosome Aberrations Recombination Genetic 0303 health sciences Anophthalmia ved/biology Zebrafish Proteins medicine.disease eye diseases Non-homologous end joining Coloboma Disease Models Animal Phenotype Karyotyping Bone Morphogenetic Proteins 030221 ophthalmology & optometry Female Chromosomes Human Pair 8 |
| Zdroj: | Asai-Coakwell, M, French, C R, Berry, K M, Ye, M, Koss, R, Somerville, M, Mueller, R, van Heyningen, V, Waskiewicz, A J & Lehmann, O J 2007, ' GDF6, a novel locus for a spectrum of ocular developmental anomalies ', American Journal of Human Genetics, vol. 80, no. 2, pp. 306-15 . https://doi.org/10.1086/511280 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/511280 |
| Popis: | Colobomata represent visually impairing ocular closure defects that are associated with a diverse range of developmental anomalies. Characterization of a chromosome 8q21.2-q22.1 segmental deletion in a patient with chorioretinal coloboma revealed elements of nonallelic homologous recombination and nonhomologous end joining. This genomic architecture extends the range of chromosomal rearrangements associated with human disease and indicates that a broader spectrum of human chromosomal rearrangements may use coupled homologous and nonhomologous mechanisms. We also demonstrate that the segmental deletion encompasses GDF6, encoding a member of the bone-morphogenetic protein family, and that inhibition of gdf6a in a model organism accurately recapitulates the proband’s phenotype. The spectrum of disorders generated by morpholino inhibition and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrate the key role of GDF6 in ocular development. These results underscore the value of integrated clinical and molecular investigation of patients with chromosomal anomalies. |
| Databáze: | OpenAIRE |
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