Talal Mousallem, MD, Thomas J. Urban, PharmD, PhD, K

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Presentation transcript:

Clinical application of whole-genome sequencing in patients with primary immunodeficiency Talal Mousallem, MD, Thomas J. Urban, PharmD, PhD, K. Melodi McSweeney, BS, Sarah E. Kleinstein, MS, Mingfu Zhu, PhD, Mehdi Adeli, MD, Roberta E. Parrott, BS, Joseph L. Roberts, MD, PhD, Brian Krueger, PhD, Rebecca H. Buckley, MD, David B. Goldstein, PhD Journal of Allergy and Clinical Immunology Volume 136, Issue 2, Pages 476-479.e6 (August 2015) DOI: 10.1016/j.jaci.2015.02.040 Copyright © 2015 Terms and Conditions

Fig 1 Semi-quantitative PCR and quantitative real-time PCR results of minigene expression. A, Minigene-1 (IVS1+1G>T) mRNA expression. B, Quantitative Taqman results showing only 16% expression of the WT mRNA in Minigene-1. C, Minigene-5 (IVS5+2T>A) mRNA expression. D, Sanger sequencing confirmation of IVS5+2T>A, resulting in exon 5 skipping. GAPDH, Glyceraldehyde 3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2015 136, 476-479.e6DOI: (10.1016/j.jaci.2015.02.040) Copyright © 2015 Terms and Conditions

Fig 2 DCLRE1C protein assays. A, FLAG-tag insertion in exon 14 of the WT-DCLRE1C construct and exon 6 of the Δexon5 construct. B, Semi-quantitative PCR showing the presence of Δexon5 mRNA expression. C, Immunoblotting showing the absence of DCLRE1C protein expression in mutant Δexon5 isoform. GAPDH, Glyceraldehyde 3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2015 136, 476-479.e6DOI: (10.1016/j.jaci.2015.02.040) Copyright © 2015 Terms and Conditions

Fig E1 Detection of CNVs by ERDS. A read depth (RD) of 40 indicates that both copies of the gene are present; an RD of 20 suggests that 1 gene copy is missing; an RD of 0 suggests that both gene copies are missing. Detection of 82-kb deletion on chromosome 10 including exons 1 to 4 of DCLRE1C in patients 4 (A), 5 (B), and 6 (C). The deletion is homozygous in patient 4. Journal of Allergy and Clinical Immunology 2015 136, 476-479.e6DOI: (10.1016/j.jaci.2015.02.040) Copyright © 2015 Terms and Conditions

Fig E2 Sanger confirmation of IVS1+G>T and IVS5+2T>A DCLRE1C variant constructs. Journal of Allergy and Clinical Immunology 2015 136, 476-479.e6DOI: (10.1016/j.jaci.2015.02.040) Copyright © 2015 Terms and Conditions