Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly

Publication date: 22 February 2018 Source:Cell, Volume 172, Issue 5 Author(s): Tatsiana Aneichyk, William T. Hendriks, Rachita Yadav, David Shin, Dadi Gao, Christine A. Vaine, Ryan L. Collins, Aloysius Domingo, Benjamin Currall, Alexei Stortchevoi, Trisha Multhaupt-Buell, Ellen B. Penney, Lilian Cruz, Jyotsna Dhakal, Harrison Brand, Carrie Hanscom, Caroline Antolik, Marisela Dy, Ashok Ragavendran, Jason Underwood, Stuart Cantsilieris, Katherine M. Munson, Evan E. Eichler, Patrick Acuña, Criscely Go, R. Dominic G. Jamora, Raymond L. Rosales, Deanna M. Church, Stephen R. Williams, Sarah Garcia, Christine Klein, Ulrich Müller, Kirk C. Wilhelmsen, H. T. Marc Timmers, Yechiam Sapir, Brian J. Wainger, Daniel Henderson, Naoto Ito, Neil Weisenfeld, David Jaffe, Nutan Sharma, Xandra O. Breakefield, Laurie J. Ozelius, D. Cristopher Bragg, Michael E. Talkowski X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcri...
Source: Cell - Category: Cytology Source Type: research