20 research outputs found

    Analysis of case-control study type I error rates from 3 simulated SNPs within <i>BDNF</i>.

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    <p>The three SNPs show allele frequency differences between CEU and YRI of 0.066 (rs11030108), 0.102 (rs10767658), and 0.233 (rs1013402). The y-axis is estimated type I error rate versus the simulated CEU proportion (x-axis). Panels on the left show data with a difference in disease prevalence ratio of 1.25 while a ratio of 1.5 is shown on the right.</p

    Estimated odds ratios (OR) from case-control analysis of 3 simulated SNPs within <i>BDNF</i>.

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    <p>Conventions are the same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019699#pone-0019699-g002" target="_blank">Figure 2</a> except the y-axis is the average estimated OR from the same analysis as presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019699#pone-0019699-g002" target="_blank">Figure 2</a>.</p

    Descriptive statistics on the number of identical genotypes between all possible pairing of samples by group.

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    <p>Descriptive statistics on the number of identical genotypes between all possible pairing of samples by group.</p

    Chronological Changes in MicroRNA Expression in the Developing Human Brain

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    <div><p>Objective</p><p>MicroRNAs (miRNAs) are endogenously expressed noncoding RNA molecules that are believed to regulate multiple neurobiological processes. Expression studies have revealed distinct temporal expression patterns in the developing rodent and porcine brain, but comprehensive profiling in the developing human brain has not been previously reported.</p><p>Methods</p><p>We performed microarray and TaqMan-based expression analysis of all annotated mature miRNAs (miRBase 10.0) as well as 373 novel, predicted miRNAs. Expression levels were measured in 48 post-mortem brain tissue samples, representing gestational ages 14–24 weeks, as well as early postnatal and adult time points.</p><p>Results</p><p>Expression levels of 312 miRNAs changed significantly between at least two of the broad age categories, defined as fetal, young, and adult.</p><p>Conclusions</p><p>We have constructed a miRNA expression atlas of the developing human brain, and we propose a classification scheme to guide future studies of neurobiological function.</p></div

    Detection of population structure in four HapMap populations.

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    <p>The first two principal components from EIGENSTRAT are plotted for all 3 SNP panels (A, SNP panel 93; B, SNP panel 52; C, SNP panel 19). As more AIMs are used in the analysis, the resolution improves. The 52 SNP panel appears to have some overlap between CEU and CHB+JPT though it should be noted that these datapoints are more clearly differentiated by considering the third and fourth principal components (not shown).</p

    Demographic information of brain tissue donors.

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    <p>samples excluded from expression analysis.</p><p>UMB# – Sample identifier, NICHD Brain and Tissues Bank for Developmental Disorders.</p><p>GA – gestational age.</p><p>Pool – indicates sample pooling for TaqMan arrays.</p><p>PMI – post-mortem interval (hours).</p

    Temporal expression analysis using real-time quantitative PCR.

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    <p>The number of miRNAs that exceed the indicated fold difference are tabulated for each pair-wise sample type comparison.</p

    Autism Associated Gene, <i>ENGRAILED2</i>, and Flanking Gene Levels Are Altered in Post-Mortem Cerebellum

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    <div><p>Background</p><p>Previous genetic studies demonstrated association between the transcription factor <i>ENGRAILED2</i> (<i>EN2</i>) and Autism Spectrum Disorder (ASD). Subsequent molecular analysis determined that the <i>EN2</i> ASD-associated haplotype (<i>rs1861972</i>-<i>rs1861973</i> A-C) functions as a transcriptional activator to increase gene expression. <i>EN2</i> is flanked by 5 genes, <i>SEROTONIN RECEPTOR5A (HTR5A), INSULIN INDUCED GENE1 (INSIG1)</i>, <i>CANOPY1 HOMOLOG (CNPY1), RNA BINDING MOTIF PROTEIN33 (RBM33)</i>, and <i>SONIC HEDGEHOG (SHH)</i>. These flanking genes are co-expressed with <i>EN2</i> during development and coordinate similar developmental processes. To investigate if mRNA levels for these genes are altered in individuals with autism, post-mortem analysis was performed.</p><p>Methods</p><p>qRT-PCR quantified mRNA levels for <i>EN2</i> and the 5 flanking genes in 78 post-mortem cerebellar samples. mRNA levels were correlated with both affection status and <i>rs1861972-rs1861973</i> genotype. Molecular analysis investigated whether <i>EN2</i> regulates flanking gene expression.</p><p>Results</p><p><i>EN2</i> levels are increased in affected A-C/G-T individuals (pβ€Š=β€Š.0077). Affected individuals also display a significant increase in <i>SHH</i> and a decrease in <i>INSIG1</i> levels. <i>Rs1861972</i>-<i>rs1861973</i> genotype is correlated with significant increases for <i>SHH</i> (A-C/G-T) and <i>CNPY1</i> (G-T/G-T) levels. Human cell line over-expression and knock-down as well as mouse knock-out analysis are consistent with <i>EN2</i> and <i>SHH</i> being co-regulated, which provides a possible mechanism for increased <i>SHH</i> post-mortem levels.</p><p>Conclusions</p><p><i>EN2</i> levels are increased in affected individuals with an A-C/G-T genotype, supporting <i>EN2</i> as an ASD susceptibility gene. <i>SHH</i>, <i>CNPY1</i>, and <i>INSIG1</i> levels are also significantly altered depending upon affection status or <i>rs1861972</i>-<i>rs1861973</i> genotype. Increased <i>EN2</i> levels likely contribute to elevated <i>SHH</i> expression observed in the post-mortem samples</p></div

    Overview of Included Studies and Sample Sizes.

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    <p><sup>1</sup> Total sample sizes by Population Group are Nβ€Š=β€Š346 African American, Nβ€Š=β€Š352 European American, Nβ€Š=β€Š574 Han Chinese and Nβ€Š=β€Š280 Hispanic.</p><p><sup>2</sup> This count omits 100 pedigree IDs dropped prior to processing, primarily due to uninformativeness for linkage or duplication across Studies 6, 7.</p><p><sup>3</sup> 15 families were dropped (and 3 subsumed by joining) prior to this stage, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084696#pone.0084696.s001" target="_blank">Appendix S1</a> & <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084696#pone.0084696.s005" target="_blank">Table S1</a> for details.</p><p><sup>4</sup> Families used in this paper to compare results across the four data configurations are those remaining after genotype processing with at least two schizophrenia cases according to either the HGI or CAPS clinical criteria, omitting 16 such families with bitsize larger than 24 for computational reasons.</p><p><sup>5</sup> Study 7 included trios in the published total.</p

    Effects of data processing on (a) number of affected individuals<sup>1</sup> and (b) number of multiplex families<sup>2</sup>.

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    <p>S1 through S7 indicate study numbers. The bars represent Human Genetics Initiative (HGI) and Combined Analysis of Psychiatric Studies (CAPS) data. <sup>1</sup>HGI diagnosis includes SZ, SA, SADD, NSPECT and BSPECT; CAPS diagnosis includes Schizophrenia and Schizophrenia/Affective as defined in the text. <sup>2</sup>HGI includes all 1,413 families with at least two affected individuals by HGI criteria; CAPS includes all 1,046 families with at least two affected individuals by CAPS criteria. Note that analyses presented in the main text utilized the subset of pedigrees satisfying both criteria.</p
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