Watson, CM, Camm, N, Crinnion, LA et al. (6 more authors) (2017) Characterization and Genomic Localization of a SMAD4 Processed Pseudogene. Journal of Molecular Diagnostics, 19 (6). pp. 933-940. ISSN 1525-1578
Abstract
Like many clinical diagnostic laboratories, we undertake routine investigation of cancer-predisposed individuals by high-throughput sequencing of patient DNA that has been target-enriched for genes associated with hereditary cancer. Accurate diagnosis using such reagents requires alertness against rare nonpathogenic variants that may interfere with variant calling. In a cohort of 2042 such cases, we identified five that initially appeared to be carriers of a 95-bp deletion of SMAD4 intron 6. More detailed analysis indicated that these individuals all carried one copy of a SMAD4 processed gene. Because of its interference with diagnostic analysis, we characterized this processed gene in detail. Whole genome sequencing and confirmatory Sanger sequencing of junction PCR products were used to show that in each of the five cases, the SMAD4 processed gene was integrated at the same position on chromosome 9, located within the last intron of the SCAI gene. This rare polymorphic processed gene therefore reflects the occurrence of a single ancestral retrotransposition event. Compared to the reference SMAD4 mRNA sequence NM_005359.5 (https://www.ncbi.nlm.nih.gov/nucleotide/), the 5′ and 3′ UTR regions of the processed gene are both truncated, but its open reading frame is unaltered. Our experience leads us to advocate the use of an RNA-seq aligner, as part of diagnostic assay quality assurance, since this allows their recognition in a comparatively facile automated fashion.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017, Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology and the Association for Molecular Pathology. This is an author produced version of a paper published in The Journal of Molecular Diagnostics. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Genetics (LIBACS) (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Translational Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Sep 2017 16:10 |
Last Modified: | 01 Sep 2018 00:39 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jmoldx.2017.08.002 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:121101 |