Genetic diagnosis of Mendelian disorders via RNA sequencing

Nature Communications

Volumn 8, Issue , 2017, Pages

  Kremer, Laura S ^a,b   Bader, Daniel M ^c,d   Mertes, Christian ^c   Kopajtich, Robert ^a,b   Pichler, Garwin ^e   Iuso, Arcangela ^a,b   Haack, Tobias B ^a,b,r   Graf, Elisabeth ^a,b   Schwarzmayr, Thomas ^a,b   Terrile, Caterina ^a   Koňaříkova, Eliška ^a,b   Repp, Birgit ^a,b   Kastenmüller, Gabi ^a   Adamski, Jerzy ^a   Lichtner, Peter ^a   Leonhardt, Christoph ^f   Funalot, Benoit ^g   Donati, Alice ^h   Tiranti, Valeria ⁱ   Lombes, Anne ^j,k   Jardel, Claude ^j,l   Gläser, Dieter ^m   Taylor, Robert W ⁿ   Ghezzi, Daniele ⁱ   Mayr, Johannes A ^o   Rötig, Agnes ^g   Freisinger, Peter ^p   Distelmaier, Felix ^q   Strom, Tim M ^a,b   Meitinger, Thomas ^a,b   Gagneur, Julien ^c,d   Prokisch, Holger ^a,b   more..

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^d UNIVERSITY OF MUNICH   (Germany)

^e MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

^f Neuropädiatrie   (Germany)

^g IMAGINE INSTITUTE   (France)

^h UNIVERSITY OF FLORENCE   (Italy)

ⁱ DEPARTMENT OF NEUROSURGERY   (Italy)

^j INSTITUT COCHIN   (France)

^k UNIVERSITÉ PARIS DESCARTES   (France)

^l ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^m Genetikum   (Germany)

ⁿ NEWCASTLE UNIVERSITY   (United Kingdom)

^o PARACELSUS MEDICAL UNIVERSITY   (Austria)

^p Klinikum Reutlingen   (Germany)

^q UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^r UNIVERSITY OF TÜBINGEN   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DEHYDROGENASE; ALDH18A1 PROTEIN; CYTOCHROME C OXIDASE; ENDOPEPTIDASE CLP; GLUTATHIONE TRANSFERASE; MCOLN1 PROTEIN; MGST1 PROTEIN; MITOCHONDRIAL PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); RNA; TIMMDC1 PROTEIN; UBIQUINOL CYTOCHROME C REDUCTASE; UNCLASSIFIED DRUG;

CELLS AND CELL COMPONENTS; DETECTION METHOD; DISEASE; GENE EXPRESSION; GENETIC ANALYSIS; GENOME; RNA;

ARTICLE; CHILD; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DIAGNOSTIC TEST ACCURACY STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOWN REGULATION; EXON; EXON SKIPPING; FIBROBLAST CELL LINE; GENE EXPRESSION; GENE FREQUENCY; GENETIC DISORDER; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; HUMAN CELL; HUMAN TISSUE; LOSS OF FUNCTION MUTATION; MALE; MENDELIAN DISORDER; MOLECULAR DIAGNOSIS; NEWBORN; NORMAL HUMAN; PRESCHOOL CHILD; RNA SEQUENCE; SANGER SEQUENCING; SPLICING DEFECT; TRANSCRIPTOMICS; WHOLE EXOME SEQUENCING; DIAGNOSTIC PROCEDURE; GENE EXPRESSION PROFILING; GENETICS; RNA SPLICING; SEQUENCE ANALYSIS;

DIAGNOSTIC TECHNIQUES AND PROCEDURES; GENE EXPRESSION PROFILING; HUMANS; MITOCHONDRIAL DISEASES; RNA SPLICING; SEQUENCE ANALYSIS, RNA;

EID: 85020697287     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms15824     Document Type: Article

References (68)

1. Wortmann, S. B., Koolen, D. A., Smeitink, J. A., van den Heuvel, L. & Rodenburg, R. J. Whole exome sequencing of suspected mitochondrial patients in clinical practice. J. Inherit. Metab. Dis. 38, 437-443 (2015).
2. 1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68-74 (2015).
3. Sudmant, P. H. et al. An integrated map of structural variation in 2, 504 human genomes. Nature 526, 75-81 (2015).
4. Taylor, J. C. et al. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat. Genet. 47, 717-726 (2015).
5. Li, X. et al. The impact of rare variation on gene expression across tissues. bioRxiv doi: 10. 1101/074443 (2016).
6. Zeng, Y. et al. Aberrant gene expression in humans. PLoS Genet. 11, 1-20 (2015).
7. Guan, J. et al. Exploiting aberrant mRNA expression in autism for gene discovery and diagnosis. Hum. Genet. 135, 1-15 (2016).
8. Zhao, J. et al. A burden of rare variants associated with extremes of gene expression in human peripheral blood. Am. J. Hum. Genet. 98, 299-309 (2016).
9. Albers, C. A. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat. Genet. 44, 435-439 S1-2 (2012).
10. Reinius, B. & Sandberg, R. Random monoallelic expression of autosomal genes: stochastic transcription and allele-level regulation. Nat. Rev. Genet. 16, 653-664 (2015).
11. Eckersley-Maslin, M. A. & Spector, D. L. Random monoallelic expression: regulating gene expression one allele at a time. Trends Genet. 30, 237-244 (2014).
12. Tazi, J., Bakkour, N. & Stamm, S. Alternative splicing and disease. Biochim. Biophys. Acta 1792, 14-26 2009.
13. Scotti, M. M. & Swanson, M. S. RNA mis-splicing in disease. Nat. Rev. Genet. 17, 19-32 (2015).
14. Singh, R. K. & Cooper, T. A. Pre-mRNA splicing in disease and therapeutics. Trends Mol. Med. 18, 472-482 (2012).
15. Xiong, H. Y. et al. The human splicing code reveals new insights into the genetic determinants of disease. Science 347, 1254806-1254806 (2015).
16. Muntoni, F., Torelli, S. & Ferlini, A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2, 731-740 (2003).
17. Gonorazky, H. et al. RNAseq analysis for the diagnosis of muscular dystrophy. Ann. Clin. Transl. Neurol. 3, 55-60 (2016).
18. Morel, C. F. et al. A LMNA splicing mutation in two sisters with severe dunnigan-type familial partial lipodystrophy type 2. J. Clin. Endocrinol. Metab. 91, 2689-2695 (2006).
19. Qu, Y. et al. A rare variant (c. 863G> T) in exon 7 of SMN1 disrupts mRNA splicing and is responsible for spinal muscular atrophy. Eur. J. Hum. Genet. 24, 864-870 (2016).
20. Gorman, G. S. et al. Mitochondrial diseases. Nat. Rev. Dis. Primer 2, 16080 (2016).
21. Elstner, M., Andreoli, C. & Ahting, U. MitoP2: an integrative tool for the analysis of the mitochondrial proteome. Mol. Biotechnol. 40, 306-315 (2008).
22. Mayr, J. A. et al. Spectrum of combined respiratory chain defects. J. Inherit. Metab. Dis. 38, 629-640 (2015).
23. Haack, T. B. et al. ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. Am. J. Hum. Genet. 93, 211-223 (2013).
24. Haack, T. B. et al. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nat. Genet. 42, 1131-1134 (2010).
25. Li, Y. I. et al. RNA splicing is a primary link between genetic variation and disease. Science 352, 600-604 (2016).
26. Zhang, B. et al. Proteogenomic characterization of human colon and rectal cancer. Nature 513, 382-387 (2014).
27. Liu, Y., Beyer, A. & Aebersold, R. On the dependency of cellular protein levels on mRNA abundance. Cell 165, 535-550 (2016).
28. Lee, K. K., Shimoji, M., Hossain, Q. S., Sunakawa, H. & Aniya, Y. Novel function of glutathione transferase in rat liver mitochondrial membrane: role for cytochrome c release from mitochondria. Toxicol. Appl. Pharmacol. 232, 109-118 (2008).
29. Holzerova, E. et al. Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration. Brain 139, 346-354 (2016).
30. Guarani, V. et al. TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex. Mol. Cell. Biol. 34, 847-861 (2014).
31. Andrews, B., Carroll, J., Ding, S., Fearnley, I. M. & Walker, J. E. Assembly factors for the membrane arm of human complex I. Proc. Natl Acad. Sci. USA 110, 18934-18939 (2013).
32. Pervouchine, D. D., Knowles, D. G. & Guig, R. Intron-centric estimation of alternative splicing from RNA-seq data. Bioinformatics 29, 273-274 (2013).
33. Lek, M. et al. Analysis of protein-coding genetic variation in 60, 706 humans. Nature 536, 285-291 (2016).
34. Halperin, T., Zheng, B., Itzhaki, H., Clarke, A. K. & Adam, Z. Plant mitochondria contain proteolytic and regulatory subunits of the ATP-dependent Clp protease. Plant Mol. Biol. 45, 461-468 (2001).
35. Jenkinson, E. M. et al. Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. Am. J. Hum. Genet. 92, 605-613 (2013).
36. Jenkinson, E. M. et al. Perrault syndrome: further evidence for genetic heterogeneity. J. Neurol. 259, 974-976 (2012).
37. Szczepanowska, K. et al. CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels. EMBO J. 35, 2566-2583 (2016).
38. Piva, F., Giulietti, M., Burini, A. B. & Principato, G. SpliceAid 2: a database of human splicing factors expression data and RNA target motifs. Hum. Mutat. 33, 81-85 (2012).
39. Dogan, R. I., Getoor, L., Wilbur, W. J. & Mount, S. M. SplicePort-an interactive splice-site analysis tool. Nucleic Acids Res. 35, W285-W291 (2007).
40. Timmermans, M. J. T. N. et al. Why barcode High-throughput multiplex sequencing of mitochondrial genomes for molecular systematics. Nucleic Acids Res. 38, e197-e197 (2010).
41. Desmet, F.-O. et al. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 37, e67 (2009).
42. Yeo, G., Hoon, S., Venkatesh, B. & Burge, C. B. Variation in sequence and organization of splicing regulatory elements in vertebrate genes. Proc. Natl Acad. Sci. USA 101, 15700-15705 (2004).
43. Burge, C. & Karlin, S. Prediction of complete gene structures in human genomic DNA. J. Mol. Biol. 268, 78-94 (1997).
44. Kapustin, Y. et al. Cryptic splice sites and split genes. Nucleic Acids Res. 39, 5837-5844 (2011).
45. Adams, E. & Frank, L. Metabolism of proline and the hydroxyprolines. Annu. Rev. Biochem. 49, 1005-1061 (1980).
46. Baumgartner, M. R. et al. Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Hum. Mol. Genet. 9, 2853-2858 (2000).
47. Fischer-Zirnsak, B. et al. Recurrent de novo mutations affecting residue Arg138 of pyrroline-5-carboxylate synthase cause a progeroid form of autosomal-dominant cutis laxa. Am. J. Hum. Genet. 97, 483-492 (2015).
48. Coutelier, M. et al. Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. Brain 138, 2191-2205 (2015).
49. Sibley, C. R., Blazquez, L. & Ule, J. Lessons from non-canonical splicing. Nat. Rev. Genet. 17, 407-421 (2016).
50. Cummings, B. B. et al. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Sci. Transl. Med 9, eaal5209 (2017).
51. Gibson, G. Human genetics. GTEx detects genetic effects. Science 348, 640-641 (2015).
52. Vafai, S. B. & Mootha, V. K. Mitochondrial disorders as windows into an ancient organelle. Nature 491, 374-383 (2012).
53. Gagneur, J. et al. Genotype-environment interactions reveal causal pathways that mediate genetic effects on phenotype. PLoS Genet. 9, e1003803 (2013).
54. Mayr, J. A. et al. Lack of the mitochondrial protein acylglycerol kinase causes sengers syndrome. Am. J. Hum. Genet. 90, 314-320 (2012).
55. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).
56. Li, H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 27, 2987-2993 (2011).
57. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078-2079 (2009).
58. McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 26, 2069-2070 (2010).
59. Eilbeck, K. et al. The Sequence Ontology: a tool for the unification of genome annotations. Genome Biol. 6, R44 (2005).
60. Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15-21 (2013).
61. Hsu, F. et al. The UCSC known genes. Bioinformatics 22, 1036-1046 (2006).
62. Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118 (2013).
63. Anders, S. & Huber, W. DESeq: differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010).
64. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
65. Hochberg, Y. A sharper bonferroni procedure for multiple tests of significance. Biometrika 75, 800-802 (1988).
66. Li, Y. I., Knowles, D. A. & Pritchard, J. K. LeafCutter: annotation-free quantification of RNA splicing. bioRxiv doi: 10. 1101/044107 (2016).
67. Harrow, J. et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 22, 1760-1774 (2012).
68. Van Haute, L. et al. Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat. Commun. 7, 12039 (2016).