@article {628,
	title = {Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly.},
	journal = {Cell},
	volume = {172},
	year = {2018},
	month = {2018 02 22},
	pages = {897-909.e21},
	abstract = {<p>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 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression. CRISPR/Cas9 excision of the SVA rescued this XDP-specific~transcriptional signature and normalized TAF1 expression in probands. These data suggest an SVA-mediated aberrant transcriptional mechanism associated with XDP and may provide a roadmap for layered technologies and integrated assembly-based analyses for other unsolved Mendelian disorders.</p>},
	keywords = {Alternative Splicing, Alu Elements, Base Sequence, Cohort Studies, CRISPR-Cas Systems, Dystonic Disorders, Family, Female, Genetic Diseases, X-Linked, Genetic Loci, Genome, Human, Haplotypes, High-Throughput Nucleotide Sequencing, Histone Acetyltransferases, Humans, Induced Pluripotent Stem Cells, Introns, Male, Minisatellite Repeats, Models, Genetic, Nerve Degeneration, Neural Stem Cells, Neurons, RNA, Messenger, Short Interspersed Nucleotide Elements, TATA-Binding Protein Associated Factors, Transcription Factor TFIID, Transcriptome},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2018.02.011},
	author = {Aneichyk, Tatsiana and Hendriks, William T and Yadav, Rachita and Shin, David and Gao, Dadi and Vaine, Christine A and Collins, Ryan L and Domingo, Aloysius and Currall, Benjamin and Stortchevoi, Alexei and Multhaupt-Buell, Trisha and Penney, Ellen B and Cruz, Lilian and Dhakal, Jyotsna and Brand, Harrison and Hanscom, Carrie and Antolik, Caroline and Dy, Marisela and Ragavendran, Ashok and Underwood, Jason and Cantsilieris, Stuart and Munson, Katherine M and Eichler, Evan E and Acu{\~n}a, Patrick and Go, Criscely and Jamora, R Dominic G and Rosales, Raymond L and Church, Deanna M and Williams, Stephen R and Garcia, Sarah and Klein, Christine and M{\"u}ller, Ulrich and Wilhelmsen, Kirk C and Timmers, H T Marc and Sapir, Yechiam and Wainger, Brian J and Henderson, Daniel and Ito, Naoto and Weisenfeld, Neil and Jaffe, David and Sharma, Nutan and Breakefield, Xandra O and Ozelius, Laurie J and Bragg, D Cristopher and Talkowski, Michael E}
}
@article {406,
	title = {SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.},
	journal = {Nat Genet},
	volume = {49},
	year = {2017},
	month = {2017 Feb},
	pages = {238-248},
	abstract = {<p>Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84\% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.</p>},
	keywords = {Adolescent, Child, Child, Preschool, Choanal Atresia, Chromosomal Proteins, Non-Histone, Female, Genetic Predisposition to Disease, Humans, Infant, Male, Microphthalmos, Muscular Dystrophies, Mutation, Nose, Phenotype},
	issn = {1546-1718},
	doi = {10.1038/ng.3743},
	author = {Shaw, Natalie D and Brand, Harrison and Kupchinsky, Zachary A and Bengani, Hemant and Plummer, Lacey and Jones, Takako I and Erdin, Serkan and Williamson, Kathleen A and Rainger, Joe and Stortchevoi, Alexei and Samocha, Kaitlin and Currall, Benjamin B and Dunican, Donncha S and Collins, Ryan L and Willer, Jason R and Lek, Angela and Lek, Monkol and Nassan, Malik and Pereira, Shahrin and Kammin, Tammy and Lucente, Diane and Silva, Alexandra and Seabra, Catarina M and Chiang, Colby and An, Yu and Ansari, Morad and Rainger, Jacqueline K and Joss, Shelagh and Smith, Jill Clayton and Lippincott, Margaret F and Singh, Sylvia S and Patel, Nirav and Jing, Jenny W and Law, Jennifer R and Ferraro, Nalton and Verloes, Alain and Rauch, Anita and Steindl, Katharina and Zweier, Markus and Scheer, Ianina and Sato, Daisuke and Okamoto, Nobuhiko and Jacobsen, Christina and Tryggestad, Jeanie and Chernausek, Steven and Schimmenti, Lisa A and Brasseur, Benjamin and Cesaretti, Claudia and Garc{\'\i}a-Ortiz, Jose E and Buitrago, Tatiana Pineda and Silva, Orlando Perez and Hoffman, Jodi D and M{\"u}hlbauer, Wolfgang and Ruprecht, Klaus W and Loeys, Bart L and Shino, Masato and Kaindl, Angela M and Cho, Chie-Hee and Morton, Cynthia C and Meehan, Richard R and van Heyningen, Veronica and Liao, Eric C and Balasubramanian, Ravikumar and Hall, Janet E and Seminara, Stephanie B and Macarthur, Daniel and Moore, Steven A and Yoshiura, Koh-Ichiro and Gusella, James F and Marsh, Joseph A and Graham, John M and Lin, Angela E and Katsanis, Nicholas and Jones, Peter L and Crowley, William F and Davis, Erica E and FitzPatrick, David R and Talkowski, Michael E}
}
