12 research outputs found
Number of correct responses produced by the two participant groups as a function of the statement (Ironic and Literal) and of the speaker (Sarcastic and Non-sarcastic).
<p>Error bars are standard deviations. * p<.0005; ** p<.0001.</p
Mockery ratings (1 = not at all mocking and 7 = extremely mocking) of the speaker statement by the two participant groups as a function of the statement (Ironic and Literal) and of the occupation (Sarcastic and Non-sarcastic).
<p>Error bars are standard deviations. * = p<.05; ** = p<.0001.</p
Irony ratings (1 = not at all ironic and 7 = extremely ironic) of the speaker statement by the two participant groups as a function of the statement (Ironic and Literal) and of the occupation (Sarcastic and Non-sarcastic).
<p>Error bars are standard deviations. * = p<.05; ** = p<.0001.</p
Politeness ratings (1 = not at all polite and 7 = extremely polite) of the speaker statement by the two participant groups as a function of the statement (Ironic and Literal) and of the occupation (Sarcastic and Non-sarcastic).
<p>Error bars are standard deviations. * = p<.05; ** = p<.0001.</p
Characterization of the functional impact of <i>SHANK2</i> mutations in cultured neuronal cells.
<p>A. The colocalization of <i>ProSAP1A/SHANK2</i>-EGFP (postsynaptic marker) and Bassoon (presynaptic marker) indicated that the mutations did not disturb the formation of SHANK2 clusters at excitatory synapses along the dendrites. B. The quantification of synapse density was performed on 20 transfected hippocampal neurons per construct from at least three independent experiments. The majority of the <i>ProSAP1A</i> variants affecting a conserved amino acid among SHANK proteins reduced significantly the synaptic density compared with the variants that affect amino acid non conserved among SHANK proteins (Mann-Whitney U-test: n<sub>WT</sub> = 20, n<sub>mut</sub> = 20; U<sub>S557N</sub> = 82.5, p<sub>S557N</sub> = 0.001; U<sub>R569H</sub> = 124, p<sub>R569H</sub> = 0.04; U<sub>L629P</sub> = 149, p<sub>L629P</sub> = 0.17; U<sub>V717F</sub> = 114, p<sub>V717F</sub> = 0.02; U<sub>A729T</sub> = 73, p<sub>A729T</sub> = 0.000; U<sub>K780Q</sub> = 154, p<sub>K780Q</sub> = 0.221; U<sub>R818H</sub> = 108, p<sub>R818H</sub> = 0.012; U<sub>A822T</sub> = 154.5, p<sub>A822T</sub> = 0.224; U<sub>V823M</sub> = 129, p<sub>V823M</sub> = 0.056; U<sub>Y967C</sub> = 134, p<sub>Y967C</sub> = 0.076; U<sub>G1170R</sub> = 78, p<sub>G1170R</sub> = 0.001; U<sub>R1290W</sub> = 142, p<sub>R1290W</sub> = 0.121; U<sub>Q1308R</sub> = 162, p<sub>Q1308R</sub> = 0.314; U<sub>D1535N</sub> = 97, p<sub>D1535N</sub> = 0.005; U<sub>P1586L</sub> = 137, p<sub>P1586L</sub> = 0.910; U<sub>L1722P</sub> = 79, p<sub>L1722P</sub> = 0.001, *p<0.05, **p<0.01, ***p<0.001). <b>C.</b> Effect of the variants on synaptic density. The y-axis represents −log P compared to WT (P obtained with Mann-Whitney test). After Bonferroni correction for 16 tests, only P values<0.003 were considered as significant. Variants represented in red were specific to ASD, in orange were shared by ASD and controls, and in green were specific to the controls. Open circles and filled circles represent non conserved and conserved amino acids, respectively. Prim, primary; second, secondary.</p
Genetic alterations identified in the control subject SWE_Q56_508.
<p>A. <i>SHANK2</i> splice mutation (IVS22+1G>T) detected in a Swedish female control, SWE_Q56_508. The mutation altered the donor splicing site of exon 22 and led to a premature stop in all <i>SHANK2</i> isoforms except for the <i>AF1411901</i> isoform, where it altered the protein sequence (G263V). B. CNVs in the same individual altering <i>LOC339822</i>, <i>SNTG2</i>, <i>PXDN</i> and <i>MYT1L</i>. The two close duplications span 264 kb and 245 kb on chromosome 2 and altered <i>LOC339822</i> and <i>SNTG2</i>, and <i>PXDN</i> and <i>MYT1L</i>, respectively. Dots show the B allele frequency (BAF; in green), Log R ratio (LRR; in red), and QuantiSNP score (in blue). Lower panel: all CNVs listed in the Database of Genomic Variants (DGV) are represented: loss (in red), gain (in blue), gain or loss (in brown). H, homer binding site; D, dynamin binding site; C, cortactin binding site.</p
<i>SHANK2</i> mutations in patients with ASD.
<p>A. A heterozygous deletion of <i>SHANK2</i> was identified with the Illumina Human 1M-Duo SNP array in a patient with autism (AU038_3). The deletion spans 421 kb on chromosome 11q13.3, covers twelve exons of the human <i>SHANK2</i> and is not present in the parents. Each dot shows Log R Ratio (LRR; in red) and B allele frequency (BAF; in green). QuantiSNP score is represented with a blue line and indicates the deletion size. B. Location of the CNV and sequence variants (from this study and Berkel <i>et al.</i> 2010) along the SHANK2 protein: in red the variations specific to ASD, in orange the variations shared by ASD and controls and in green the variations specific to controls <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002521#pgen.1002521-Berkel1" target="_blank">[26]</a>. The breakpoints of the <i>SHANK2</i> deletion in AU038_3 are represented with a dotted line on the protein. Stars indicate the variants affecting conserved amino acids. C. A total of 40 variants were identified and variants affecting conserved amino acids in other SHANK proteins are enriched in patients with ASD (n<sub>conserved</sub> = 12 and n<sub>non-conserved</sub> = 3) compared with controls (n<sub>conserved</sub> = 6 and n<sub>non-conserved</sub> = 11) (Fisher's exact test 1-sided, P = 0.013, OR = 6.83, 95% IC = 1.19–53.40). D. The percentage of carriers of <i>SHANK2</i> variants in patients with ASD and Controls. Variants affecting a conserved amino acid among the SHANK proteins are enriched in patients with ASD (n<sub>conserved</sub> = 29 and n<sub>non-conserved</sub> = 822) compared with controls (n<sub>conserved</sub> = 16 and n<sub>non-conserved</sub> = 1074) (Fisher's exact test 1-sided, P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). Open squares and filled squares represent the non-conserved and conserved amino acids, respectively. ANK, Ankyrin repeat domain; SH3, Src homology 3 domain; PDZ, postsynaptic density 95/Discs large/zona occludens-1 homology domain; SAM, sterile alpha motif domain; BSR, brain specific region; H, homer binding site; D, dynamin binding site; C, cortactin binding site. The proline-rich region is represented as a horizontal gray line.</p
Characterization of CNVs in three patients carrying a <i>de novo</i> deletion of <i>SHANK2</i>.
<p>Paternally or maternally inherited CNVs are indicated by squares and circles, respectively. <i>De novo</i> CNVs are indicated by stars. Deletions and duplications are indicated in red and blue, respectively. CNVs hitting exons or only introns are filled with grey and white, respectively. Squares and circles within star represent <i>de novo</i> CNV of paternal or maternal origin; circles within squares represent CNV inherited by father or mother. ABCC6, ATP-binding cassette, sub-family C, member 6 pseudogene 2; ADAM, ADAM metallopeptidase; AMY1, amylase (salivary); AMY2A, amylase (pancreatic); ARHGAP11B, Rho GTPase activating protein 11B; CAMSAP1L1, calmodulin regulated spectrin-associated protein 1-like 1; CHRNA7, cholinergic receptor, nicotinic, alpha 7; CNTN4, contactin 4; CTNNA3, catenin (cadherin-associated protein), alpha 3; CYFIP1, cytoplasmic FMR1 interacting protein 1; DUSP22, dual specificity phosphatase 22; GALM, galactose mutarotase; GCNT2, glucosaminyl (N-acetyl) transferase 2; GOLGA, golgi autoantigen, golgin subfamily a; GSTT1, glutathione S-transferase theta 1; HLA-DRB, major histocompatibility complex, class II, DR beta; LAMA4, laminin, alpha 4; NIPA, non imprinted in Prader-Willi/Angelman syndrome; NLGN1, neuroligin 1; NME7, non-metastatic cells 7; OR, olfactory receptor; PCDHA, protocadherin alpha; RFPL4B, ret finger protein-like 4B; RHD, Rh blood group, D antigen; SFMBT1, Scm-like with four mbt domains 1; SHANK2, SH3 and multiple ankyrin repeat domains 2; SMC2, structural maintenance of chromosomes 2; TNS3, tensin 3; TUBGCP5, tubulin, gamma complex associated protein 5; UGT2B17, UDP glucuronosyltransferase 2 family, polypeptide B17.</p
<i>ProSAP1A/SHANK2</i> variations identified in 851 patients with ASD and 1,090 controls.
a<p>Nucleotide positions are according to <i>NM 012309.3</i> from NCBI36/hg18 on the positive DNA strand; The patients with ASD and the controls used for this analysis came from this study (455 ASD & 431 controls) and from the study of Berkel <i>et al.</i> 2010 (396 ASD & 659 controls);</p>b<p>A screening of V717F, A729T, R818H, G1170R, D1535N and L1722P was performed in 948 subjects from the Human Genome Diversity Panel (V717F = 0/948; A729T = 0/948; R818H = 5/948; G1170R = 0/948; D1535N = 0/948; L1722P = 0/948);</p>c<p>A screen of R818H was performed in additional patients and controls (ASD 32/3250 (1.0%); controls 27/2030 (1.33%); Fisher's exact test 2-sided, P = 0.28). Fisher's exact test was used for statistical analysis;</p>d<p>“Yes” indicates if amino acid is conserved in SHANK1 (S1), SHANK3 (S3) or both (S1 & S3); MAF, Minor Allele Frequency.</p