Spinocerebellar ataxia is a progressive neurodegenerative disorder with autosomal dominant inheritance. The first symptoms may occur in the second or third decade where the patient may have already started a family. Presently there is no accurate method of presymptomatic or prenatal diagnosis of this severely disabliting disease. The biology and structure of the ataxia genes are totally unknown at this time. One form of spinocerebellar ataxia is known to be linked to the HLA genes on chromosome 6. We propose to use family studies in order to map the gene for the HLA-linked spinocerebellar ataxia with greater accuracy and to subsequently clone that gene. This project can be achieved through the use of the most recent advances in recombinant DNA technology.
The specific aims are (1) to establish detailed linkage map on each side of the ataxia gene relying on the use of DNA restriction fragment length polymorphisms; (2) to narrow down the DNA region by analysis of crossovers; (3) to obtain an overlapping set of DNA clones which will bridge between the flanking markers by using gene walking techniques; and 4) to identify the spinocerebellar ataxia gene utilizing Southern transfer techniques, analysis of genomic clones and studies of RNA expression.
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