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Subject: search.filters.subject.Chondrodysplasia

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    Investigation into the inheritance and biochemistry of chondrodysplasia in Texel sheep : a thesis presented in partial fulfilment of the requirements for the Master of Science at Massey University, Palmerston North, New Zealand
    (Massey University, 2005) Byrne, Timothy John
    A skeletal chondrodysplasia characterized by dwarfism and angular deformity of the forelimbs has been recognized over four seasons in Texel and Texel cross lambs on three related properties. Some affected lambs have normal co-twins indicating that the disease is not dietary, but likely to be the result of a genetic disorder. This study reports on the inheritance and biochemistry of this newly discovered chondrodysplasia in Texel sheep. The outcome of a backcross trial between putative carrier ewes and affected rams provided evidence that indicated that the chondrodysplasia has an autosomal recessive mode of inheritance, and that it is likely to be caused by a single gene defect. Analysis of proteoglycan constituents of cartilage by SDS-PAGE, followed by sulfate-specific staining indicated that the biochemical abnormality lies in the level of sulfation of proteoglycans in the extracellular matrix of affected animals. It was also shown by SDS-PAGE that there were no differences in the major collagen constituents of cartilage between unaffected and affected animals. A candidate gene, the diastrophic dysplasia sulfate transporter, was determined based on its involvement in the process of sulfation of proteoglycans and its involvement in characterized human dysplasias, which resemble Texel chondrodysplasia both phenotypically and biochemically. PCR amplification and sequencing of 85.4 % of this gene revealed no nucleotide differences between the exonic DNA of normal, carrier, and affected animals. While this reduced the likelihood that this gene is causative in the chondrodysplasia, it does not eliminate it as a candidate, based on the fact that a mutation may exist in the region not sequenced, including the possibility of splice site mutations.
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    Chondrodysplasia of Texel sheep : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand
    (Massey University, 2008) Piripi, Susan Amanda
    Chondrodysplasia of Texel sheep is a newly described recessively inherited disorder distinct from other chondrodysplasias described in sheep. Phenotypically normal at birth, affected lambs develop microscopic lesions as early as 9 days of age, and usually demonstrate gross deformities and markedly reduced rates of bone growth by 2 to 3 weeks. Individual bone growth rates are most severely affected in the proximal bones of the forelimbs. Chondrodysplastic lambs typically have short stature, angular limb deformities, a barrel-shaped chest and a wide-based stance. Gross lesions include tracheal narrowing and contortion, enlarged costochondral junctions, and erosion of articular cartilage in major limb joints. Microscopic lesions are confined to hyaline cartilage, and are characterised by degeneration of the interterritorial matrix and dense perichondrocytic rings consisting predominantly of type VI collagen. These lesions are identical in appearance to those in achondrogenesis 1b and diastrophic dysplasia, two diseases caused by defects of the diastrophic dysplasia sulphate transporter (DTDST) in human beings. An investigation to measure the uptake of radiolabelled sulphate by dermal fibroblasts in vitro did not provide evidence of a defect in the DTDST in chondrodysplastic Texel sheep. A linkage disequilibrium study of ovine chromosomes 1, 5, 6, 13 and 22 using microsatellite DNA markers was unable to identify evidence of a mutation causing this form of chondrodysplasia. Capillary electrophoresis of unsaturated chondroitin sulphate disaccharides demonstrated a relative reduction in the ratio of chondroitin 4-sulphate to chondroitin 6-sulphate in affected animals of all ages. This biochemical feature enables the potential determination of the phenotype of newborn lambs prior to the emergence of gross or microscopic lesions. The pathology of the disease, combined with the findings of the genetic, biochemical and in vitro studies, suggest that a mutation may be present in the CHST11 gene. This gene is a good candidate for future studies aimed at discovering the genetic defect in chondrodysplasia of Texel sheep and developing a test to identify heterozygous animals.