<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Guo, Hui</style></author><author><style face="normal" font="default" size="100%">Duyzend, Michael H</style></author><author><style face="normal" font="default" size="100%">Coe, Bradley P</style></author><author><style face="normal" font="default" size="100%">Baker, Carl</style></author><author><style face="normal" font="default" size="100%">Hoekzema, Kendra</style></author><author><style face="normal" font="default" size="100%">Gerdts, Jennifer</style></author><author><style face="normal" font="default" size="100%">Turner, Tychele N</style></author><author><style face="normal" font="default" size="100%">Zody, Michael C</style></author><author><style face="normal" font="default" size="100%">Beighley, Jennifer S</style></author><author><style face="normal" font="default" size="100%">Murali, Shwetha C</style></author><author><style face="normal" font="default" size="100%">Nelson, Bradley J</style></author><author><style face="normal" font="default" size="100%">Bamshad, Michael J</style></author><author><style face="normal" font="default" size="100%">Nickerson, Deborah A</style></author><author><style face="normal" font="default" size="100%">Bernier, Raphael A</style></author><author><style face="normal" font="default" size="100%">Eichler, Evan E</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">University of Washington Center for Mendelian Genomics</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.</style></title><secondary-title><style face="normal" font="default" size="100%">Genet Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Genet. Med.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Jul</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">21</style></volume><pages><style face="normal" font="default" size="100%">1611-1620</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;PURPOSE: &lt;/b&gt;To maximize the discovery of potentially pathogenic variants to better understand the diagnostic utility of genome sequencing (GS) and to assess how the presence of multiple risk events might affect the phenotypic severity in autism spectrum disorders (ASD).&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;GS was applied to 180 simplex and multiplex ASD families (578 individuals, 213 patients) with exome sequencing and array comparative genomic hybridization further applied to a subset for validation and cross-platform comparisons.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;We found that 40.8% of patients carried variants with evidence of disease risk, including a de novo frameshift variant in NR4A2 and two de novo missense variants in SYNCRIP, while 21.1% carried clinically relevant pathogenic or likely pathogenic variants. Patients with more than one risk variant (9.9%) were more severely affected with respect to cognitive ability compared with patients with a single or no-risk variant. We observed no instance among the 27 multiplex families where a pathogenic or likely pathogenic variant was transmitted to all affected members in the family.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;The study demonstrates the diagnostic utility of GS, especially for multiple risk variants that contribute to the phenotypic severity, shows the genetic heterogeneity in multiplex families, and provides evidence for new genes for follow up.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/30504930?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Turner, Tychele N</style></author><author><style face="normal" font="default" size="100%">Coe, Bradley P</style></author><author><style face="normal" font="default" size="100%">Dickel, Diane E</style></author><author><style face="normal" font="default" size="100%">Hoekzema, Kendra</style></author><author><style face="normal" font="default" size="100%">Nelson, Bradley J</style></author><author><style face="normal" font="default" size="100%">Zody, Michael C</style></author><author><style face="normal" font="default" size="100%">Kronenberg, Zev N</style></author><author><style face="normal" font="default" size="100%">Hormozdiari, Fereydoun</style></author><author><style face="normal" font="default" size="100%">Raja, Archana</style></author><author><style face="normal" font="default" size="100%">Pennacchio, Len A</style></author><author><style face="normal" font="default" size="100%">Darnell, Robert B</style></author><author><style face="normal" font="default" size="100%">Eichler, Evan E</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genomic Patterns of De Novo Mutation in Simplex Autism.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Autistic Disorder</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Copy Number Variations</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Mutational Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">INDEL Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Oct 19</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">171</style></volume><pages><style face="normal" font="default" size="100%">710-722.e12</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;To further our understanding of the genetic etiology of autism, we generated and analyzed genome sequence data from 516 idiopathic autism families (2,064 individuals). This resource includes &gt;59 million single-nucleotide variants (SNVs) and 9,212 private copy number variants (CNVs), of which 133,992 and 88 are de novo mutations (DNMs), respectively. We estimate a mutation rate of ∼1.5 × 10 SNVs per site per generation with a significantly higher mutation rate in repetitive DNA. Comparing probands and unaffected siblings, we observe several DNM trends. Probands carry more gene-disruptive CNVs and SNVs, resulting in severe missense mutations and mapping to predicted fetal brain promoters and embryonic stem cell enhancers. These differences become more pronounced for autism genes (p = 1.8 × 10, OR = 2.2). Patients are more likely to carry multiple coding and noncoding DNMs in different genes, which are enriched for expression in striatal neurons (p = 3 × 10), suggesting a path forward for genetically characterizing more complex cases of autism.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/28965761?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Turner, Tychele N</style></author><author><style face="normal" font="default" size="100%">Hormozdiari, Fereydoun</style></author><author><style face="normal" font="default" size="100%">Duyzend, Michael H</style></author><author><style face="normal" font="default" size="100%">McClymont, Sarah A</style></author><author><style face="normal" font="default" size="100%">Hook, Paul W</style></author><author><style face="normal" font="default" size="100%">Iossifov, Ivan</style></author><author><style face="normal" font="default" size="100%">Raja, Archana</style></author><author><style face="normal" font="default" size="100%">Baker, Carl</style></author><author><style face="normal" font="default" size="100%">Hoekzema, Kendra</style></author><author><style face="normal" font="default" size="100%">Stessman, Holly A</style></author><author><style face="normal" font="default" size="100%">Zody, Michael C</style></author><author><style face="normal" font="default" size="100%">Nelson, Bradley J</style></author><author><style face="normal" font="default" size="100%">Huddleston, John</style></author><author><style face="normal" font="default" size="100%">Sandstrom, Richard</style></author><author><style face="normal" font="default" size="100%">Smith, Joshua D</style></author><author><style face="normal" font="default" size="100%">Hanna, David</style></author><author><style face="normal" font="default" size="100%">Swanson, James M</style></author><author><style face="normal" font="default" size="100%">Faustman, Elaine M</style></author><author><style face="normal" font="default" size="100%">Bamshad, Michael J</style></author><author><style face="normal" font="default" size="100%">Stamatoyannopoulos, John</style></author><author><style face="normal" font="default" size="100%">Nickerson, Deborah A</style></author><author><style face="normal" font="default" size="100%">McCallion, Andrew S</style></author><author><style face="normal" font="default" size="100%">Darnell, Robert</style></author><author><style face="normal" font="default" size="100%">Eichler, Evan E</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Autistic Disorder</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Exome</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Human</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Jan 07</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">98</style></volume><pages><style face="normal" font="default" size="100%">58-74</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0.03) enrichment of de novo and private disruptive mutations within fetal CNS DNase I hypersensitive sites (i.e., putative regulatory regions). This effect was only observed within 50 kb of genes that have been previously associated with autism risk, including genes where dosage sensitivity has already been established by recurrent disruptive de novo protein-coding mutations (ARID1B, SCN2A, NR3C2, PRKCA, and DSCAM). In addition, we provide evidence of gene-disruptive CNVs (in DISC1, WNT7A, RBFOX1, and MBD5), as well as smaller de novo CNVs and exon-specific SNVs missed by exome sequencing in neurodevelopmental genes (e.g., CANX, SAE1, and PIK3CA). Our results suggest that the detection of smaller, often multiple CNVs affecting putative regulatory elements might help explain additional risk of simplex autism.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/26749308?dopt=Abstract</style></custom1></record></records></xml>