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dc.contributor.authorCowley, MJ
dc.contributor.authorLiu, Y-C
dc.contributor.authorOliver, KL
dc.contributor.authorCarvill, G
dc.contributor.authorMyers, CT
dc.contributor.authorGayevskiy, V
dc.contributor.authorDelatycki, M
dc.contributor.authorVlaskamp, DRM
dc.contributor.authorZhu, Y
dc.contributor.authorMefford, H
dc.contributor.authorBuckley, MF
dc.contributor.authorBahlo, M
dc.contributor.authorScheffer, IE
dc.contributor.authorDinger, ME
dc.contributor.authorRoscioli, T
dc.date.accessioned2020-12-09T23:58:07Z
dc.date.available2020-12-09T23:58:07Z
dc.date.issued2019-04-01
dc.identifier.citationCowley, M. J., Liu, Y. -C., Oliver, K. L., Carvill, G., Myers, C. T., Gayevskiy, V., Delatycki, M., Vlaskamp, D. R. M., Zhu, Y., Mefford, H., Buckley, M. F., Bahlo, M., Scheffer, I. E., Dinger, M. E. & Roscioli, T. (2019). Reanalysis and optimisation of bioinformatic pipelines is critical for mutation detection. HUMAN MUTATION, 40 (4), pp.374-379. https://doi.org/10.1002/humu.23699.
dc.identifier.issn1059-7794
dc.identifier.urihttp://hdl.handle.net/11343/253377
dc.description.abstractRapid advances in genomic technologies have facilitated the identification pathogenic variants causing human disease. We report siblings with developmental and epileptic encephalopathy due to a novel, shared heterozygous pathogenic 13 bp duplication in SYNGAP1 (c.435_447dup, p.(L150Vfs*6)) that was identified by whole genome sequencing (WGS). The pathogenic variant had escaped earlier detection via two methodologies: whole exome sequencing and high-depth targeted sequencing. Both technologies had produced reads carrying the variant, however, they were either not aligned due to the size of the insertion or aligned to multiple major histocompatibility complex (MHC) regions in the hg19 reference genome, making the critical reads unavailable for variant calling. The WGS pipeline followed different protocols, including alignment of reads to the GRCh37 reference genome, which lacks the additional MHC contigs. Our findings highlight the benefit of using orthogonal clinical bioinformatic pipelines and all relevant inheritance patterns to re-analyze genomic data in undiagnosed patients.
dc.languageEnglish
dc.publisherWILEY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleReanalysis and optimisation of bioinformatic pipelines is critical for mutation detection
dc.typeJournal Article
dc.identifier.doi10.1002/humu.23699
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleHuman Mutation
melbourne.source.volume40
melbourne.source.issue4
melbourne.source.pages374-379
melbourne.identifier.nhmrc1091593
melbourne.identifier.nhmrc1104831
dc.rights.licenseCC BY
melbourne.elementsid1362935
melbourne.contributor.authorScheffer, Ingrid
melbourne.contributor.authorBahlo, Melanie
melbourne.contributor.authorBroderick, Karen
melbourne.contributor.authorDelatycki, Martin
melbourne.contributor.authorLiu, Yu-Chi
dc.identifier.eissn1098-1004
melbourne.identifier.fundernameidNHMRC, 1091593
melbourne.identifier.fundernameidNHMRC, 1104831
melbourne.accessrightsOpen Access


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