Seminário Suporte à pesquisa e gestão de dados científicos: panorama atual e desafios, 1.: materiais de divulgação

Primeiro Seminário Suporte à pesquisa e gestão de dados científicos: panorama atual e desafios, realizado entre os dias 18 e 19 de setembro de 2017, no Auditório do Espaço Físico Integrado, da UFSC. Contém banner e folder produzidos para divulgação do evento, elaborados pela estagiária Aila Lima. Banner armazenado na arara 26 do arquivo deslizante da Memória Documental BU.PGCIN/UFSC e Biblioteca Universitária/UFSC

Localization of C-terminally GFP-tagged EDNRB fusion proteins in HEK293 cells.

<p>A: HEK293 cells were transiently transfected with wild-type EDNRB isoform 1 (Iso 1) or mutant EDNRB isoform 1 (M1V). Signals were observed at the plasma membrane in cells expressing wild-type isform 1 while signals were detected in the cytosol in cells transfected with mutant isoform 1. B: HEK293 cells were transiently transfected with wild-type EDNRB isoform 3 (Iso 3) or mutant EDNRB isoform 3 (M91V). Signals were found in the cytosol in cells transfected with either wild-type or mutant isoform 3. C. HEK293 cells were transiently transfected with GFP vector only. Shown are the representative iamges. Bars, 50 µm.</p

Pedigree of the three-generation family included in this study.

<p>Slash: deceased. Solid black: individuals affected with HSCR only. Green: individual affected with HSCR and heterochromia iridum. Yellow: individual affected with HSCR and meningocele. + indicates <i>EDNRB</i> c.1A>G; * indicates <i>EDN3</i> c.-248G>A.</p

Genome-Wide Copy Number Analysis Uncovers a New HSCR Gene: <em>NRG3</em>

<div><p>Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified <em>NRG1</em> as a new HSCR susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched controls showed that HSCR patients have a greater burden of rare CNVs (<em>p</em> = 1.50×10⁻⁵), particularly for those encompassing genes (<em>p</em> = 5.00×10⁻⁶). Our study identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a <em>NRG3</em> deletion (<em>p</em> = 1.64×10⁻³). Subsequent follow-up (96 additional patients and 220 controls) on <em>NRG3</em> revealed 9 deletions (combined <em>p</em> = 3.36×10⁻⁵) and 2 <em>de novo</em> duplications among patients and two deletions among controls. Importantly, <em>NRG3</em> is a paralog of <em>NRG1</em>. Stratification of patients by presence/absence of HSCR–associated syndromes showed that while syndromic–HSCR patients carried significantly longer CNVs than the non-syndromic or controls (<em>p</em> = 1.50×10⁻⁵), non-syndromic patients were enriched in CNV number when compared to controls (<em>p</em> = 4.00×10⁻⁶) or the syndromic counterpart. Our results suggest a role for <em>NRG3</em> in HSCR etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic HSCR. This would be the first genome-wide catalog of copy number variants identified in HSCR.</p> </div

Global CNV burden in HSCR patients.

a<p>Rate: number of CNVs per individual.</p>b<p>Baseline: size, rate or gene count of controls.</p>c<p>Ratio: Case/control ratio.</p>d<p><i>P</i>-value for conditional permutation based on score of LRR_SD, BAF_drift and median absolute deviation.</p>e<p>Del+Dup of all rare CNVs was specified as above.</p>*<p>0.01<<i>p</i><0.05;</p>**<p>10⁻⁴<<i>p</i><0.01;</p>***<p><i>p</i><10⁻⁴.</p

CNV burden for syndromic (Syn) and non-syndromic (Non-syn) HSCR patients relative to controls (Ctrl).

<p>The burden was measured with reference to the (A) size, (B) rate and (C) gene count of CNVs. Red and blue bars denote the mean value of the corresponding test for deletion and duplication respectively. Summary statistics as well as conditional permutation <i>p</i>-value was shown in (D).</p

<i>NRG3</i> deletions identified in HSCR patients.

<p>(A) Intensity signals of 5 HSCR patients (CN = 1; red) with <i>NRG3</i> deletions together with other samples of normal copy number (CN = 2; grey). Deleted regions are shown by the dark red bar and are highlighted in pink. (B) Consensus CNV segments of the 5 <i>NRG3</i> deletions (red) and the overlapping DGV segments (blue; with DGV ID). (C, D and E) Box plot of <i>NRG3</i> copy number estimates by real-time PCR. Samples were grouped according to the called copy number states (CN = 1, red; CN = 2, white; CN = 3, blue); (C) Validation of 5 deletions (CN = 1) and 24 copy-neutral (CN = 2) HSCR patients in the discovery phase; (D) Follow-up analysis on independent case-controls set and (E) Transmission analysis for probands with <i>NRG3</i> deletions (child CN = 1) or duplications (child CN = 3). (F) Sequence of the <i>NRG3</i> deletion boundary region showing the breakpoint (upstream boundary chr10: 84032610; downstream boundary chr10: 84052262).</p

Large (>1 Mb), rare CNVs identified in HSCR patients.

a<p>S: Syndromic patient; NS: non-syndromic patient.</p>b<p>Genes overlapped by recurrent CNVs unique to patients.</p>c<p>S27 have 2 overlapping duplications within the 16p11-12 locus.</p

Additional file 7: Table S6. of Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes

Gene recurrence and burden test. (XLSX 14 kb

Additional file 9: Table S8. of Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes

Characteristics of 116 ENS-related HSCR candidate genes. (XLSX 32 kb