GSE96099
3' sequencing from human Huntington''s disease and control motor cortex and cerebellum.
Purpose: We applied polyA site sequencing (Passeq) to human Huntington''s disease and control motor cortex and cerebellum to test if any genes change 3'UTR isoforms abundance. Methods: 3' sequencing was performed on 6 motor cortices from grade 1 Huntington''s patient brains, 4 motor cortices from grade 2 Huntington''s patient brains, and 5 motor cortices from control brains.  Cerebellum samples included 9 cerebella from grade 2-3 Huntington''s patient brains, and 7 cerebella from control brains. To verify HTT isoforms in mice, sequencing was performed on 5 Q140 mouse striata and 3 wild-type mouse striata. Results: We report 11% of genes from Huntington''s disease patient motor cortex exhibit a change in at least one of their 3'UTR isoforms, commensurate with the 11% of genes which show different total expression in HD motor cortex versus control.  In contrast, gene isoform and expression changes are minimal (<5%) in Huntington''s disease cerebellum versus controls. In the motor cortex, we show isoform and gene expression differs between between grade 1 and grade 2 brains.  We identify a novel isoform of huntingtin mRNA which is conserved in wild-type and Huntington''s model mice. Conclusions: This is the first study characterizing widespread alterations in 3'UTR isoform abundance in Huntington''s disease.  Alterations in isoform abundance may affect mRNA metabolism in Huntington''s disease brains. Overall design: Examination of 3'UTR isoform abundance in Huntington''s disease and control motor cortex and cerebellum, and in Q140 and wild-type mouse striatum. 3' sequencing was performed on 6 motor cortices from grade 1 Huntington''s patient brains, 4 motor cortices from grade 2 Huntington''s patient brains, and 5 motor cortices from control brains.  Cerebellum samples included 9 cerebella from grade 2-3 Huntington''s patient brains, and 7 cerebella from control brains. To verify HTT isoforms in mice, sequencing was performed on 5 Q140 mouse striata and 3 wild-type mouse striata.