This application requests five years of support to establish a Center for Genomic and Phenomic Studies in Autism involving the University of Southern California (USC), Autism Genetic Resource Exchange (AGRE), MIND Institute/University of California (UC) - Davis, University of Michigan, Children's Hospital Los Angeles (CHLA), and E.K. Shriver Center/University of Massachusetts Medical School. The Center brings together a distinguished multidisciplinary team of investigators with considerable expertise in the genomics and phenomics of autism in multiplex pedigrees, including nationwide family ascertainment and screening, high throughput diagnostics, state-of-the-art clinical evaluation and structural interviewing, cognitive and behavioral evaluations, 3D craniofacial morphology, cytogenetics, DMA microarrays, immunology, structural brain imaging, electrophysiology, and environmental risk assessment. Our research team also has considerable experience in coordinating and widely distributing to the scientific community phenomic and genomic information in autism. We have identified over 1,400 pedigrees with two or more affected children, for which comprehensive clinical data, DMA and cell lines are currently distributed through AGRE and the NIMH Human Genetics Initiative. The Center will utilize a nationwide ascertainment strategy with a demonstrated record of success and collect state-of-the-art high-throughput phenotypic information and blood from a new ethnically diverse sample of 1,500 multiplex autism pedigrees that will be shared with the National Database for Autism Research (NDAR) and the NIMH Human Genetics Initiative. High-throughput phenomics conducted on affected children will include state-of-the-art clinical instrumentation and structural interviews to assess behavioral, social, cognitive/intellectual, language/communicative and adaptive functioning. Cytogenetic and baseline environmental risk assessments also will be made. Pilot studies in a subset of 625 autistic children in California will be conducted to identify robust endophenotypes using state of- the-art technologies for 3D craniofacial morphology, structural brain imaging, DNA microarrays, immunological assays, auditory evoked potentials and other psychophysiological measures, and air quality assessments. Unique strengths of our proposal include: (1) the inclusion of established programs at AGRE and the MIND Institute/UC - Davis that will utilize pre-existing infrastructure, including USC/CHLA's General Clinical Research Center; (2) AGRE's considerable experience in establishing a nationwide collection of phenomic and genomic resources for autism research; and (3) the availability of highly efficient bioinformatics algorithms and a web-based data management system. The ultimate goal of our Center will be to facilitate genetic and environmental studies on autism, thereby improving diagnosis, accelerating our understanding of its etiology and pathophysiology, and facilitating discovery of new therapeutics. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
1U24MH081810-01
Application #
7347923
Study Section
Special Emphasis Panel (ZMH1-ERB-C (03))
Program Officer
Yao, Yin Y
Project Start
2007-09-28
Project End
2012-05-31
Budget Start
2007-09-28
Budget End
2008-05-31
Support Year
1
Fiscal Year
2007
Total Cost
$1,597,220
Indirect Cost
Name
University of Southern California
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Kalkbrenner, Amy E; Windham, Gayle C; Zheng, Cheng et al. (2018) Air Toxics in Relation to Autism Diagnosis, Phenotype, and Severity in a U.S. Family-Based Study. Environ Health Perspect 126:037004
Tangsuwansri, Chayanin; Saeliw, Thanit; Thongkorn, Surangrat et al. (2018) Investigation of epigenetic regulatory networks associated with autism spectrum disorder (ASD) by integrated global LINE-1 methylation and gene expression profiling analyses. PLoS One 13:e0201071
Shen, Mark D; Nordahl, Christine W; Li, Deana D et al. (2018) Extra-axial cerebrospinal fluid in high-risk and normal-risk children with autism aged 2-4 years: a case-control study. Lancet Psychiatry 5:895-904
Evrony, Gilad D; Cordero, Dwight R; Shen, Jun et al. (2017) Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome. Genome Res 27:1323-1335
Stessman, Holly A F; Xiong, Bo; Coe, Bradley P et al. (2017) Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet 49:515-526
Geisheker, Madeleine R; Heymann, Gabriel; Wang, Tianyun et al. (2017) Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains. Nat Neurosci 20:1043-1051
Naigles, Letitia R; Johnson, Ryan; Mastergeorge, Ann et al. (2017) Neural correlates of language variability in preschool-aged boys with autism spectrum disorder. Autism Res 10:1107-1119
Careaga, Milo; Rogers, Sally; Hansen, Robin L et al. (2017) Immune Endophenotypes in Children With Autism Spectrum Disorder. Biol Psychiatry 81:434-441
Tai, Derek J C; Ragavendran, Ashok; Manavalan, Poornima et al. (2016) Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR. Nat Neurosci 19:517-22
Poopal, Ashwini C; Schroeder, Lindsay M; Horn, Paul S et al. (2016) Increased expression of the PI3K catalytic subunit p110? underlies elevated S6 phosphorylation and protein synthesis in an individual with autism from a multiplex family. Mol Autism 7:3

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