Transcriptomics

Dataset Information

7

Gene expression profiling of lymphoblastoid cell lines from autistic and nonaffected sib pairs


ABSTRACT: Despite the identification of numerous autism susceptibility genes, the pathobiology of autism remains unknown. The present “case-control” study takes a global approach to understanding the molecular basis of autism spectrum disorders based upon large-scale gene expression profiling. DNA microarray analyses were conducted on lymphoblastoid cell lines from over 20 sib pairs in which one sibling had a diagnosis of autism and the other was not affected in order to identify biochemical and signaling pathways which are differentially regulated in cells from autistic and nonautistic siblings. Bioinformatics and gene ontological analyses of the data implicate genes which are involved in nervous system development, inflammation, and cytoskeletal organization, in addition to genes which may be relevant to gastrointestinal or other physiological symptoms often associated with autism. Moreover, the data further suggests that these processes may be modulated by cholesterol/steroid metabolism, especially at the level of androgenic hormones. Elevation of male hormones, in turn, has been suggested as a possible factor influencing susceptibility to autism, which affects ~4 times as many males as females. Metabolic profiling of steroid hormones in lymphoblastoid cell lines from several pairs of siblings reveals higher levels of testosterone in the autistic sibling, which is consistent with the increased expression of two genes involved in the steroidogenesis pathway. Global gene expression profiling of cultured cells from ASD probands thus serves as a window to underlying metabolic and signaling deficits that may be relevant to the pathobiology of autism. Gene expression profiling of LCL from autistic (21) and nonautistic (17) siblings (4 sets of autistic twins included) were obtained using a custom-printed DNA microarray containing 39,936 elements (TIGR 40K Human array, GPL3427) and a reference design in which each sample was compared to the Stratagene Universal Human RNA standard. Following data normalization, the ratios of expression values for the autistic proband relative to his normal unaffected sibling were determined. Related siblings are identified by their common family ID# (AU****) as provided by the Autism Resource Genetic Exchange (AGRE) repository (and listed in Sample title). Differentially expressed genes were determined across all ratioed expression values for sib pairs (autistic vs. control) using one-class SAM (Statistical Analysis of Microarrays) analysis.

ORGANISM(S): Homo sapiens  

SUBMITTER: Mara E Steinberg   Michele A Scully  Valerie W Hu  Steven J Soldin  AnhThu N Nguyen  Tewarit Sarachana  Truong Luu  Norman H Lee  Valerie Hu  Kyung S Kim 

PROVIDER: E-GEOD-15451 | ArrayExpress | 2010-05-15

SECONDARY ACCESSION(S): GSE15451PRJNA115947

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis.

Hu Valerie W VW   Nguyen AnhThu A   Kim Kyung Soon KS   Steinberg Mara E ME   Sarachana Tewarit T   Scully Michele A MA   Soldin Steven J SJ   Luu Truong T   Lee Norman H NH  

PloS one 20090603 6


Despite the identification of numerous autism susceptibility genes, the pathobiology of autism remains unknown. The present "case-control" study takes a global approach to understanding the molecular basis of autism spectrum disorders based upon large-scale gene expression profiling. DNA microarray analyses were conducted on lymphoblastoid cell lines from over 20 sib pairs in which one sibling had a diagnosis of autism and the other was not affected in order to identify biochemical and signaling  ...[more]

Similar Datasets

2009-07-27 | GSE15451 | GEO
2010-04-27 | GSE21395 | GEO
2010-04-27 | E-GEOD-21395 | ArrayExpress
2006-02-08 | GSE4187 | GEO
2010-04-09 | GSE21086 | GEO
2010-04-09 | E-GEOD-21086 | ArrayExpress
2010-05-17 | E-GEOD-15402 | ArrayExpress
2009-12-22 | GSE15402 | GEO
2016-07-01 | E-GEOD-65106 | ArrayExpress
| PRJNA115947 | ENA