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Status |
Public on Feb 08, 2006 |
Title |
Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Background: The autism spectrum includes a set of complex multigenic developmental disorders that severely impact the development of language, non-verbal communication, and social skills, and are associated with odd, stereotyped, repetitive behavior and restricted interests. To date, diagnosis of these neurologically based disorders relies predominantly upon behavioral observations often prompted by delayed speech or aberrant behavior, and there are no known genes that can serve as definitive biomarkers for the disorders. Results: Here we demonstrate, for the first time, that lymphoblastoid cell lines from monozygotic twins discordant with respect to severity of autism and/or language impairment exhibit differential gene expression patterns on DNA microarrays. Furthermore, we show that genes important to the development, structure, and/or function of the nervous system are among the most differentially expressed genes, and that many of these genes map in silico to chromosomal regions containing autism susceptibility genes or quantitative trait loci. Conclusions: Our present results provide compelling evidence that candidate genes for autism may be expressed in lymphoid cell lines from individuals with autism spectrum disorders. This finding further suggests the possibility of developing a molecular screen for autism using peripheral blood lymphocytes, an easily accessible tissue. In addition, gene networks are identified that may play a role in the pathophysiology of autism. Keywords: DNA microarrays, comparison expression profiling, relation to autistic phenotype
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Overall design |
The experimental strategy used in the study reported here was designed to tease out differences in gene expression among genetically identical individuals with ASD which might relate to observed differences in degree of expression of autistic symptoms. To determine whether lymphoblastoid cell lines (LCL) derived from individuals with autism exhibit patterns of gene expression that may be relevant to autism spectrum disorders (ASD), gene expression profiling was performed on LCL derived from 5 sets of male monozygotic twins, in which the co-twins (twin siblings) differed with respect to diagnosis of autism, or the severity of language impairment. Two of twin pairs had an unaffected sibling and these were also used for comparison with their respective twin siblings. All of these assays employed a experimental design in which RNA from the co-twins (or from a twin and his nonautistic sibling) were cohybridized on two-color spotted microarrays containing 39,936 human cDNA elements. Each microarray experiment involved dye-reversal replicates, and was performed in duplicate or, in one case, triplicate for the different sets of twins.
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Contributor(s) |
Hu VW, Frank BC, Lee NH, Quackenbush J |
Citation(s) |
16709250, 20374639, 20375269 |
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Submission date |
Feb 06, 2006 |
Last update date |
Mar 16, 2012 |
Contact name |
Valerie Wailin Hu |
E-mail(s) |
valhu@gwu.edu
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Phone |
202-994-8431
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Organization name |
The George Washington University School of Medicine and Health Sciences
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Department |
Biochemistry and Molecular Medicine
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Lab |
Ross Hall 233
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Street address |
2300 Eye St., N.W., Rm232-233
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City |
Washington |
State/province |
DC |
ZIP/Postal code |
20037 |
Country |
USA |
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Platforms (1) |
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Samples (19)
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GSM95592 |
Lymphoblasts_361-360_autistic twins_rep1 |
GSM95593 |
Lymphoblasts_361-360_autistic twins_rep2 |
GSM95594 |
Lymphoblasts_HI0361_autistic twin_rep3 |
GSM95595 |
Lymphoblasts_809-810_autistic twins_rep1 |
GSM95596 |
Lymphoblasts_809-810_autistic twins_rep2 |
GSM95597 |
Lymphoblasts_2369-2368_autistic twins_rep1 |
GSM95598 |
Lymphoblasts_2369-2368_autistic twins_rep2 |
GSM95599 |
Lymphoblasts_2595-2596_autistic twins_rep1 |
GSM95600 |
Lymphoblasts_2595-2596_autistic twins_rep2 |
GSM95601 |
Lymphoblasts_2597-2598_autistic twins_rep1 |
GSM95602 |
Lymphoblasts_2597-2598_autistic twins_rep2 |
GSM95603 |
Lymphoblasts_2745-2744_nonautistic twins_rep1 |
GSM95604 |
Lymphoblasts_2745-2744_nonautistic twins_rep2 |
GSM95605 |
Lymphoblasts_809-813_autistic vs nonautistic siblings |
GSM95606 |
Lymphoblasts_810-813_mildly autistic vs nonautistic siblings |
GSM95607 |
Lymphoblasts_2368-2357_milder autistic vs nonautistic siblings_rep1 |
GSM95608 |
Lymphoblasts_2368-2357_milder autistic vs nonautistic siblings_rep2 |
GSM95609 |
Lymphoblasts_2369-2357_autistic vs nonautistic siblings_rep1 |
GSM95610 |
Lymphoblasts_2369-2357_autistic vs nonautistic siblings_rep2 |
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Relations |
BioProject |
PRJNA95153 |
Supplementary data files not provided |
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