Article Abstract:
A P1 genomic library of 17-fold coverage and a cosmid library of eight genome equivalents were ordered by hybridizing genetic markers and individual clones from the two libraries. Both were gridded on high density filters and subdivided by yeast artificial chromosome clones covering the entire genome. Further data was provided by the hybridization of short oligonucleotides and DNA pools made from randomly selected cosmids. This approach of using parallel libraries greatly enhances the mapping and resolution of the clone order, although further improvements can be made in speed and accuracy.
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Article Abstract:
Research has been undertaken into the CAG/polyglutamine-repeat expansion which is responsible for the human neurodegenerative disorder Huntington's disease (HD). It was established that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to (CAG)156 repeat expansions show clear neuronal intranuclear inclusions (NIIs) before developing a neurological phenotype. Neurons within the striatum of mice transgenic for the HD mutation contain an NII that contains the proteins htt and ubiquitin.
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Article Abstract:
Studies using mice transgenic for the 5' end of the human Huntington's disease (HD) gene carrying expanded CAG repeats have shown that the expanded CAG repeats are within exon 1 of the genomic fragment. The mice exhibited neurological disorders that are characteristic to HD such as epileptic seizures, tremor, motor abnormalities, cerebellar dysfunctions, voluntary movement disorders, as well as emotional disorders.
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