TY  - JOUR
AU  - Yépez, Vicente A
AU  - Gusic, Mirjana
AU  - Kopajtich, Robert
AU  - Mertes, Christian
AU  - Smith, Nicholas H
AU  - Alston, Charlotte L
AU  - Ban, Rui
AU  - Beblo, Skadi
AU  - Berutti, Riccardo
AU  - Blessing, Holger
AU  - Ciara, Elżbieta
AU  - Distelmaier, Felix
AU  - Freisinger, Peter
AU  - Häberle, Johannes
AU  - Hayflick, Susan J
AU  - Hempel, Maja
AU  - Itkis, Yulia S
AU  - Kishita, Yoshihito
AU  - Klopstock, Thomas
AU  - Krylova, Tatiana D
AU  - Lamperti, Costanza
AU  - Lenz, Dominic
AU  - Makowski, Christine
AU  - Mosegaard, Signe
AU  - Müller, Michaela
AU  - Muñoz-Pujol, Gerard
AU  - Nadel, Agnieszka
AU  - Ohtake, Akira
AU  - Okazaki, Yasushi
AU  - Procopio, Elena
AU  - Schwarzmayr, Thomas
AU  - Smet, Joél
AU  - Staufner, Christian
AU  - Stenton, Sarah L
AU  - Strom, Tim M
AU  - Terrile, Caterina
AU  - Tort, Frederic
AU  - Van Coster, Rudy
AU  - Vanlander, Arnaud
AU  - Wagner, Matias
AU  - Xu, Manting
AU  - Fang, Fang
AU  - Ghezzi, Daniele
AU  - Mayr, Johannes A
AU  - Piekutowska-Abramczuk, Dorota
AU  - Ribes, Antonia
AU  - Rötig, Agnès
AU  - Taylor, Robert W
AU  - Wortmann, Saskia B
AU  - Murayama, Kei
AU  - Meitinger, Thomas
AU  - Gagneur, Julien
AU  - Prokisch, Holger
TI  - Clinical implementation of RNA sequencing for Mendelian disease diagnostics.
JO  - Genome medicine
VL  - 14
IS  - 1
SN  - 1756-994X
CY  - London
PB  - BioMed Central
M1  - DZNE-2022-00439
SP  - 38
PY  - 2022
AB  - 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
KW  - Exome Sequencing
KW  - Alleles
KW  - Humans
KW  - RNA
KW  - Sequence Analysis, RNA: methods
KW  - Transcriptome
KW  - Whole Exome Sequencing
KW  - Genetic diagnostics (Other)
KW  - Mendelian diseases (Other)
KW  - RNA-seq (Other)
KW  - RNA (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35379322
C2  - pmc:PMC8981716
DO  - DOI:10.1186/s13073-022-01019-9
UR  - https://pub.dzne.de/record/163695
ER  -