%0 Journal Article
%A Yépez, Vicente A
%A Gusic, Mirjana
%A Kopajtich, Robert
%A Mertes, Christian
%A Smith, Nicholas H
%A Alston, Charlotte L
%A Ban, Rui
%A Beblo, Skadi
%A Berutti, Riccardo
%A Blessing, Holger
%A Ciara, Elżbieta
%A Distelmaier, Felix
%A Freisinger, Peter
%A Häberle, Johannes
%A Hayflick, Susan J
%A Hempel, Maja
%A Itkis, Yulia S
%A Kishita, Yoshihito
%A Klopstock, Thomas
%A Krylova, Tatiana D
%A Lamperti, Costanza
%A Lenz, Dominic
%A Makowski, Christine
%A Mosegaard, Signe
%A Müller, Michaela
%A Muñoz-Pujol, Gerard
%A Nadel, Agnieszka
%A Ohtake, Akira
%A Okazaki, Yasushi
%A Procopio, Elena
%A Schwarzmayr, Thomas
%A Smet, Joél
%A Staufner, Christian
%A Stenton, Sarah L
%A Strom, Tim M
%A Terrile, Caterina
%A Tort, Frederic
%A Van Coster, Rudy
%A Vanlander, Arnaud
%A Wagner, Matias
%A Xu, Manting
%A Fang, Fang
%A Ghezzi, Daniele
%A Mayr, Johannes A
%A Piekutowska-Abramczuk, Dorota
%A Ribes, Antonia
%A Rötig, Agnès
%A Taylor, Robert W
%A Wortmann, Saskia B
%A Murayama, Kei
%A Meitinger, Thomas
%A Gagneur, Julien
%A Prokisch, Holger
%T Clinical implementation of RNA sequencing for Mendelian disease diagnostics.
%J Genome medicine
%V 14
%N 1
%@ 1756-994X
%C London
%I BioMed Central
%M DZNE-2022-00439
%P 38
%D 2022
%X Lack of functional evidence hampers variant interpretation, leaving a large proportion of individuals with a suspected Mendelian disorder without genetic diagnosis after whole genome or whole exome sequencing (WES). Research studies advocate to further sequence transcriptomes to directly and systematically probe gene expression defects. However, collection of additional biopsies and establishment of lab workflows, analytical pipelines, and defined concepts in clinical interpretation of aberrant gene expression are still needed for adopting RNA sequencing (RNA-seq) in routine diagnostics.We implemented an automated RNA-seq protocol and a computational workflow with which we analyzed skin fibroblasts of 303 individuals with a suspected mitochondrial disease that previously underwent WES. We also assessed through simulations how aberrant expression and mono-allelic expression tests depend on RNA-seq coverage.We detected on average 12,500 genes per sample including around 60
%K Exome Sequencing
%K Alleles
%K Humans
%K RNA
%K Sequence Analysis, RNA: methods
%K Transcriptome
%K Whole Exome Sequencing
%K Genetic diagnostics (Other)
%K Mendelian diseases (Other)
%K RNA-seq (Other)
%K RNA (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35379322
%2 pmc:PMC8981716
%R 10.1186/s13073-022-01019-9
%U https://pub.dzne.de/record/163695