RNAi based allele-specific silencing of the disease-causing gene in black South African patients with SCA7

Abstract

The polyglutamine disorders are a subgroup of inherited neurodegenerative disorders with a common mutation which confers toxicity via a polyglutamine tract in the protein leading ultimately to various forms of neurodegeneration. One of these disorders, spinocerebellar ataxia 7 (SCA7) exists at a higher frequency in South Africa, than elsewhere in the world, and a founder effect has been demonstrated in South Africa, such that every patient tested thus far is linked to a common ancestor. The manipulation of RNA interference (RNAi) has been used with increasing success to selectively knockdown the expression of disease-causing genes at the RNA level. Thus, the possibility of applying this method to SCA7 in South Africa was considered. However, the wild-type allele of ataxin-7 is likely to be necessary for cellular function therefore a form of allele-specific silencing is required, such as a SNP linked to the mutation.