20 research outputs found
Top associations from the gene-level case-control collapsing analyses.
<p>Top associations from the gene-level case-control collapsing analyses.</p
Ordered correlation matrices for the PVNH query and the fourteen loci significantly co-expressing within this node.
<p>Pairwise Pearson’s correlation represented as a matrix between (a) pairs of the 14 genes within the PVNH gene set (Methods) and (b) the human PVNH query plus the 14 genes whose co-regulatory patterns significantly exceed the eFDR in both the Kang and Miller transcriptomic datasets. Genes are ordered according to hierarchical clustering, with the most positive (+1) and negative (-1) co-regulatory interactions represented as blue and red squares, respectively.</p
Genes with multiple <i>de novo</i> variants.
<p>Genes with multiple <i>de novo</i> variants.</p
Distribution of <i>MAP1B</i> LOF alleles in PVNH cases (red dots), in individuals from ExAC and gnomAD databases (blue dots with number of alleles observed represented by number of dots running vertically at this site), and in the Deciphering Developmental Disorders case (orange dot).
<p>A Sanger confirmed <i>de novo</i> variant is indicated with a white dot in the circle.</p
<i>MAP1B</i> LoF qualifying variants identified in PVNH patients.
<p><i>MAP1B</i> LoF qualifying variants identified in PVNH patients.</p
List of <i>de novo</i> and likely deleterious brain malformation CNVs ordered by their cytogenetic bands.
<p>“Known/Novel” refers to whether the CNV has been previously observed to be <i>de novo</i> in patients with one or more of the three brain malformations (Known) or not (Novel). While some of the “Novel” CNVs may previously have been implicated in other disorders, they are novel for the malformations used in this study. Double asterisks denote <i>de novo</i> CNVs at least 500 kb with high pathogenicity scores. Single asterisks denote <i>de novo</i> CNVs less than 500 kb with slightly lower pathogenicity scores. While deletions of 7q36.3 have been linked to ACC, duplications have not which is why it is “Novel”. Similarly, deletion 9p23-p22.3, which has not been observed in ACC, overlaps a known ACC region with duplications (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003823#pgen.1003823.s017" target="_blank">Table S9</a>). Many <i>de novo</i> CNVs in ACC were found to overlap <i>de novo</i> CNVs observed in autism. All CNVs listed are <i>de novo</i> except for the following five: 9p23-p22.3, 9q34.3, Xq28 (1223-0) for which inheritance could not be determined; 16p13.11 which was paternally inherited and uncovered a maternally inherited nonsense pathogenic mutation in <i>NDE1</i>; and Xq28 (LR02-148) which was maternally inherited. While patient 1574-0 has one large <i>de novo</i> deletion on 1q41-q42.13 that overlaps a well-known ACC interval, the second <i>de novo</i> deletion on 1q31.2-q31.3 is also large and likely to be deleterious.</p
Genome-wide burden of rare CNVs≥1 Mb that impacted ≥20 genes in brain malformation patients and controls.
<p>Deletions and duplications were assessed together (“±”) and also separately (“−” and “+”, respectively). Significant differences are shown by numbers on top of bars for the respective malformations. These numbers correspond to corrected p-values, odds ratios (OR), and 95% confidence intervals (CI) provided below the graph. Asterisks: while the corrected p-values were not significant (>0.05), the odds ratios and 95% confident intervals were both highly suggestive of significant differences between patients and controls.</p
Genome-wide burden of rare CNVs based on size in brain malformation patients and controls of Caucasian ethnicity.
<p>There were 205 ACC (panel A), 82 ACC-PLUS (panel B), 123 ACC-ONLY (panel C), 180 CBLH (panel D), and 121 PMG (panel E) patients, and 1,953 controls. In each malformation we examined all rare CNVs that were at least 30 kb (all CNVs≥30 kb), followed by those that were at least 1 Mb (≥1 Mb), those that were at least 500 kb but less than 1 Mb (500 kb–1 Mb), those that were at least 100 kb but less than 500 kb (100–500 kb), and those that were at least 30 kb but less than 100 kb (30–100 kb). Deletions are represented by “−” and duplications by “+”. Significant differences between patients (dark bars) and controls (light bars) are shown by black lines/hooks that connect patients and controls with numbers listed above. The numbers correspond to corrected p-values, odds ratios (OR), and 95% confidence intervals (CI) provided in the lower right. Asterisk: while the corrected p-value was not significant (0.09), the odds ratio (2.90) and 95% confident interval (1.49–5.65) were both highly suggestive of a significant difference.</p
Genome-wide burden of rare CNVs based on number of genes impacted in brain malformation patients and controls of Caucasian ethnicity.
<p>There were 205 ACC (panel A), 82 ACC-PLUS (panel B), 123 ACC-ONLY (panel C), 180 CBLH (panel D), and 121 PMG (panel E) patients, and 1,953 controls. Deletions and duplications were assessed together (“±”) and also separately (“−” and “+”, respectively). Significant differences between patients (dark bars) and controls (light bars) are shown by black lines/hooks that connect patients and controls with numbers listed above. The numbers correspond to corrected p-values, odds ratios (OR), and 95% confidence intervals (CI) provided in the lower right. Asterisk: while the corrected p-value was not significant (0.40), the odds ratio (2.96) and 95% confident interval (1.30–6.76) were both highly suggestive of a significant difference.</p
Cellular compartment association to spasm and other seizures.
<p>A schematic diagram of a neuron showing association of enriched compiled cellular compartments to either infantile spasms group or other epilepsy group. Golgi and endoplasmic reticulum (ER) and overall cell body (soma) are significantly associated with the spasms group. Dendrites and axonal regions including Node of Ranvier are significantly associated with other epilepsies.</p