Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes

  1. Demidov, German ORCID logo
  2. Laurie, Steven ORCID logo
  3. Torella, Annalaura
  4. PILUSO, Giulio ORCID logo
  5. Scala, Marcello ORCID logo
  6. Morleo, Manuela
  7. Nigro, Vincenzo
  8. Graessner, Holm ORCID logo
  9. Banka, Siddharth ORCID logo
  10. Solve-RD consortium
  11. Macaya, Alfons
  12. Pérez-Dueñas, Belén
  13. Jackson, Adam
  14. Stevanin, Giovanni
  15. de Sainte Agathe, Jean-Madeleine
  16. Havlovicová, Markéta
  17. Horvath, Rita
  18. Pinelli, Michele
  19. van Os, Nienke J. H.
  20. van de Warrenburg, Bart P. C.
  21. Denommé-Pichon, Anne-Sophie
  22. Savarese, Marco
  23. Johari, Mridul
  24. Dallapiccola, Bruno
  25. Tartaglia, Marco
  26. Pauly, Martje G.
  27. Sommer, Anna Katharina
  28. Haack, Tobias B.
  29. Töpf, Ana
  30. Didier, Lacombe
  31. Fallerini, Chiara
  32. Renieri, Alessandra
  33. Chinnery, Patrick F.
  34. Natera-de Benito, Daniel
  35. Nascimento, Andres
  36. Trimouille, Aurélien
  37. Munell, Francina
  38. Marcé-Grau, Anna
  39. Rabah, Ben Yaou
  40. Bonne, Gisèle
  41. Van de Vondel, Liedewei
  42. Lohmann, Katja ORCID logo
  43. Ossowski, Stephan ORCID logo

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1000 Titel
  • Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes
1000 Autor/in
  1. Demidov, German |
  2. Laurie, Steven |
  3. Torella, Annalaura |
  4. PILUSO, Giulio |
  5. Scala, Marcello |
  6. Morleo, Manuela |
  7. Nigro, Vincenzo |
  8. Graessner, Holm |
  9. Banka, Siddharth |
  10. Solve-RD consortium |
  11. Macaya, Alfons |
  12. Pérez-Dueñas, Belén |
  13. Jackson, Adam |
  14. Stevanin, Giovanni |
  15. de Sainte Agathe, Jean-Madeleine |
  16. Havlovicová, Markéta |
  17. Horvath, Rita |
  18. Pinelli, Michele |
  19. van Os, Nienke J. H. |
  20. van de Warrenburg, Bart P. C. |
  21. Denommé-Pichon, Anne-Sophie |
  22. Savarese, Marco |
  23. Johari, Mridul |
  24. Dallapiccola, Bruno |
  25. Tartaglia, Marco |
  26. Pauly, Martje G. |
  27. Sommer, Anna Katharina |
  28. Haack, Tobias B. |
  29. Töpf, Ana |
  30. Didier, Lacombe |
  31. Fallerini, Chiara |
  32. Renieri, Alessandra |
  33. Chinnery, Patrick F. |
  34. Natera-de Benito, Daniel |
  35. Nascimento, Andres |
  36. Trimouille, Aurélien |
  37. Munell, Francina |
  38. Marcé-Grau, Anna |
  39. Rabah, Ben Yaou |
  40. Bonne, Gisèle |
  41. Van de Vondel, Liedewei |
  42. Lohmann, Katja |
  43. Ossowski, Stephan |
1000 Verlag
  • Springer International Publishing
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-05-31
1000 Erschienen in
1000 Quellenangabe
  • 32(8):998-1004
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41431-024-01637-4 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291474/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title> <jats:p>Structural variants (SVs), including large deletions, duplications, inversions, translocations, and more complex events have the potential to disrupt gene function resulting in rare disease. Nevertheless, current pipelines and clinical decision support systems for exome sequencing (ES) tend to focus on small alterations such as single nucleotide variants (SNVs) and insertions-deletions shorter than 50 base pairs (indels). Additionally, detection and interpretation of large copy-number variants (CNVs) are frequently performed. However, detection of other types of SVs in ES data is hampered by the difficulty of identifying breakpoints in off-target (intergenic or intronic) regions, which makes robust identification of SVs challenging. In this paper, we demonstrate the utility of SV calling in ES resulting in a diagnostic yield of 0.4% (23 out of 5825 probands) for a large cohort of unsolved patients collected by the Solve-RD consortium. Remarkably, 8 out of 23 pathogenic SV were not found by comprehensive read-depth-based CNV analysis, resulting in a 0.13% increased diagnostic value.</jats:p>
1000 Sacherschließung
lokal /631/114/1314
lokal /692/308/2056
lokal Humans [MeSH]
lokal Genomic Structural Variation [MeSH]
lokal Exome Sequencing [MeSH]
lokal DNA Copy Number Variations [MeSH]
lokal Article
lokal Genetic Testing/standards [MeSH]
lokal Rare Diseases/genetics [MeSH]
lokal Genetic Testing/methods [MeSH]
lokal Rare Diseases/diagnosis [MeSH]
lokal Exome/genetics [MeSH]
lokal article
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-9075-4276|https://orcid.org/0000-0003-3913-5829|https://frl.publisso.de/adhoc/uri/VG9yZWxsYSwgQW5uYWxhdXJh|https://orcid.org/0000-0001-9418-125X|https://orcid.org/0000-0003-2194-7239|https://frl.publisso.de/adhoc/uri/TW9ybGVvLCBNYW51ZWxh|https://frl.publisso.de/adhoc/uri/Tmlncm8sIFZpbmNlbnpv|https://orcid.org/0000-0001-9803-7183|https://orcid.org/0000-0002-8527-2210|https://frl.publisso.de/adhoc/uri/U29sdmUtUkQgY29uc29ydGl1bQ==|https://frl.publisso.de/adhoc/uri/TWFjYXlhLCBBbGZvbnM=|https://frl.publisso.de/adhoc/uri/UMOpcmV6LUR1ZcOxYXMsIEJlbMOpbg==|https://frl.publisso.de/adhoc/uri/SmFja3NvbiwgQWRhbQ==|https://frl.publisso.de/adhoc/uri/U3RldmFuaW4sIEdpb3Zhbm5p|https://frl.publisso.de/adhoc/uri/ZGUgU2FpbnRlIEFnYXRoZSwgSmVhbi1NYWRlbGVpbmU=|https://frl.publisso.de/adhoc/uri/SGF2bG92aWNvdsOhLCBNYXJrw6l0YQ==|https://frl.publisso.de/adhoc/uri/SG9ydmF0aCwgUml0YQ==|https://frl.publisso.de/adhoc/uri/UGluZWxsaSwgTWljaGVsZQ==|https://frl.publisso.de/adhoc/uri/dmFuIE9zLCBOaWVua2UgSi4gSC4=|https://frl.publisso.de/adhoc/uri/dmFuIGRlIFdhcnJlbmJ1cmcsIEJhcnQgUC4gQy4=|https://frl.publisso.de/adhoc/uri/RGVub21tw6ktUGljaG9uLCBBbm5lLVNvcGhpZQ==|https://frl.publisso.de/adhoc/uri/U2F2YXJlc2UsIE1hcmNv|https://frl.publisso.de/adhoc/uri/Sm9oYXJpLCBNcmlkdWw=|https://frl.publisso.de/adhoc/uri/RGFsbGFwaWNjb2xhLCBCcnVubw==|https://frl.publisso.de/adhoc/uri/VGFydGFnbGlhLCBNYXJjbw==|https://frl.publisso.de/adhoc/uri/UGF1bHksIE1hcnRqZSBHLg==|https://frl.publisso.de/adhoc/uri/U29tbWVyLCBBbm5hIEthdGhhcmluYQ==|https://frl.publisso.de/adhoc/uri/SGFhY2ssIFRvYmlhcyBCLg==|https://frl.publisso.de/adhoc/uri/VMO2cGYsIEFuYQ==|https://frl.publisso.de/adhoc/uri/RGlkaWVyLCBMYWNvbWJl|https://frl.publisso.de/adhoc/uri/RmFsbGVyaW5pLCBDaGlhcmE=|https://frl.publisso.de/adhoc/uri/UmVuaWVyaSwgQWxlc3NhbmRyYQ==|https://frl.publisso.de/adhoc/uri/Q2hpbm5lcnksIFBhdHJpY2sgRi4=|https://frl.publisso.de/adhoc/uri/TmF0ZXJhLWRlIEJlbml0bywgRGFuaWVs|https://frl.publisso.de/adhoc/uri/TmFzY2ltZW50bywgQW5kcmVz|https://frl.publisso.de/adhoc/uri/VHJpbW91aWxsZSwgQXVyw6lsaWVu|https://frl.publisso.de/adhoc/uri/TXVuZWxsLCBGcmFuY2luYQ==|https://frl.publisso.de/adhoc/uri/TWFyY8OpLUdyYXUsIEFubmE=|https://frl.publisso.de/adhoc/uri/UmFiYWgsIEJlbiBZYW91|https://frl.publisso.de/adhoc/uri/Qm9ubmUsIEdpc8OobGU=|https://frl.publisso.de/adhoc/uri/VmFuIGRlIFZvbmRlbCwgTGllZGV3ZWk=|https://orcid.org/0000-0002-5121-1460|https://orcid.org/0000-0002-7416-9568
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