Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: CCG*CGG interruptions in high penetrance SCA8 families increase RAN translation and protein toxicity Spinocerebellar ataxia type 8 (SCA8), a dominantly inherited neurodegenerative disorder caused by a CTG*CAG expansion, is unusual because most individuals that carry the mutation do not develop ataxia. To understand the variable penetrance of SCA8 we studied the molecular differences between highly penetrant families and more common sporadic cases (82%) using a large cohort of SCA8 families (N=77). We show that repeat expansion mutations from individuals with two or more affected family members have CCG*CGG interruptions at a higher frequency than sporadic SCA8 cases and that the number of CCG*CGG interruptions correlates with age at onset. At the molecular level, CCG*CGG interruptions increase RNA hairpin stability and steady state levels of SCA8 RAN polyAla and polySer proteins. Additionally, the CCG*CGG interruptions, which encode arginine interruptions in the polyGln frame increase the toxicity of the resulting proteins. In summary, CCG*CGG interruptions increase polyAla and polySer RAN protein levels, polyGln protein toxicity and disease penetrance and provide novel insight into the molecular differences between SCA8 families with high vs. low disease penetrance.
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The categories of this paper are: pharmacology
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The categories of this paper are: plant
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The categories of this paper are: toxicology
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The categories of this paper are: zoology
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The categories of this paper are: biochemistry
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The categories of this paper are: animal
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The categories of this paper are: genomics
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The categories of this paper are: and
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The categories of this paper are: cell
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The categories of this paper are: neuroscience
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The categories of this paper are: biophysics
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The categories of this paper are: behavior
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The categories of this paper are: bioinformatics
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The categories of this paper are: cognition
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The categories of this paper are: scientific
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The categories of this paper are: communication