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Core D: Molecular Genomics Core

$64,753P01FY2007ESNIH

University Of California At Davis, Davis CA

Investigators

Linked publications & trials

Abstract

Core 4 is the Molecular Core. It serves as the central resource for the projects that isolate and process[unreadable] RNA on Affymetrix microarrays, and for performing RT-PCR confirmation of the microarray data for those[unreadable] projects. The UCD Affymetrix Core Facility is run by Dr. Jeffrey Gregg and is equipped with fluidics[unreadable] stations, hybridization ovens, and the new scanner required to scan the human Affymetrix U133 2.0PLUS[unreadable] arrays. Preliminary data from the previous CHARGE study has shown that there are changes in gene[unreadable] expression in the blood of children with autism compared to control children in the general population (GP)[unreadable] and to control children with mental retardation and developmental delay (MR/DD). The blood genomic[unreadable] profile in children with autism without regression (A) was different from controls, autism spectrum disorder[unreadable] (ASD) and different from children with autism with regression (A-R). In addition, there is a group of[unreadable] regulated genes in most children with A, A-R and with ASD that are expressed by natural killer (NK) cells[unreadable] in peripheral blood, suggesting an abnormality in this cell type that is common to all types of autism. These[unreadable] NK-cell related genes are expressed by all of the autism phenotypes including A, A-R and ASD, and hence[unreadable] may point to common pathways that underlie the common language and behavioral abnormalities in all[unreadable] three disorders. This core will be utilized by the projects as follows. Project #1: Aim #1: Perform genomic[unreadable] (RNA expression on microarrays) studies on blood from children with autism in the 4-9 year old range, and[unreadable] compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age[unreadable] range. Aim #2. Compare gene expression as a function of blood metal levels in both age groups in A, A-R,[unreadable] ASD, MR/DD and GP groups. Aim #3. Examine genomic profiles in pregnant mothers who have[unreadable] previously given birth to an autistic child to determine if there is a specific genomic profile that correlates[unreadable] with whether the mother's fetus is destined to develop autism. Project #2. Aim #1. Describe the gene[unreadable] expression profiles in the blood using specific white blood cell subsets including NK cells for children with[unreadable] autism without regression, autism with regression, and ASD children compared to GP and delayed[unreadable] children. Aim #2. Examine gene expression following stimulation or activation of specific white blood cell[unreadable] subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell[unreadable] stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics. Project #3.[unreadable] Compare gene expression profiles in the blood of children with autism to the blood of experimental animals[unreadable] exposed to toxicants including organic mercury, PCB 95, and PBDE 47 (Project #3).

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