| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
In order to identify the human chromosome which carries a mutated gene in cells from a patient with the hereditary disorder ataxia telangiectasia belonging to complementation group D (AT-D), we performed chromosome transfer experiments via microcell fusion. A single, pSV2neo-tagged chromosome, either 11 or 12, derived from normal human fibroblasts was introduced into AT-D cells by microcell fusion, and clones which were resistant to the antibiotic G418 were isolated. All 3 hybrid clones containing an additional copy number of chromosome 11 showed a restoration of the resistance of wild-type cells to killing by X-irradiaiton, whereas all 3 hybrid clones containing an additional copy number of chromosome 2 remained hyperradiosensitive, like the parental AT cells. On the other hand, the introduction ofchromosome 11 into the AT5BIVA cells suppressed X-ray-induced chromated-type aberrations to the control level, while the AT5BIVA cells was about 3.4-fold higher in the frequency of induced chromated-type aberrations than control cells. However, such a remarkable reduction was not observed in all hybrid clones containing an additional copy of chromosome 12. -The suppressive effect of chromosome aberrations by introducing chromosome -seemed to be different in types of aberrations. The introduction of chromosome 11 into the AT5BIVA cells efficiently suppressed the frequencies of gaps and breaks but not exchanges. The mean value of X-ray-induced chromated exchanges in the AT11/3 clone remained 0.45 showing a similar level in the parental AT5BIVA cells, although the mean values of gaps and breaks were 1.2 and 1.8 which were comparable to those in controls The results indicate that a defective gene of AT-D cells i also located on chromosome 11, since a genetic linkage analysis has previously suggested that a defective gene of its complementation group A is located on this chromosome.
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