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

• Published in: PloS one 2009-06, Vol.4 (6), p.e5775-e5775
• Main Authors: Hu, Valerie W, Nguyen, AnhThu, Kim, Kyung Soon, Steinberg, Mara E, Sarachana, Tewarit, Scully, Michele A, Soldin, Steven J, Luu, Truong, Lee, Norman H
• Format: Article
• Language: English
• Subjects: Autism; Autistic Disorder - genetics; Behavior; Biochemistry; Bioinformatics; Biosynthesis; Biotechnology; Brain research; Cholesterol; Chromatography; Computational Biology - methods; Cytokines; Cytoskeleton; Data processing; Deoxyribonucleic acid; Diagnosis; Disease susceptibility; DNA; DNA fingerprinting; DNA microarrays; Dopamine; Female; Females; Gene Expression; Gene Expression Profiling; Gene Regulatory Networks; Genes; Genetic aspects; Genetics; Genetics and Genomics; Genetics and Genomics/Disease Models; Genetics and Genomics/Gene Expression; Genomics; Hormones; Humans; Lipid metabolism; Lymphoblastoid cell lines; Lymphoblasts; Lymphocytes - metabolism; Male; Males; Mass spectrometry; Medical research; Metabolism; Metabolites; Molecular biology; Nervous system; Neurological Disorders/Developmental and Pediatric Neurology; Neurons; Neurons - physiology; Oligonucleotide Array Sequence Analysis; Oxidative stress; Pharmacology; Physiological aspects; Physiology; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Scientific imaging; Siblings; Signal Transduction; Steroid hormones; Steroidogenesis; Testosterone; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005775

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 approximately 4 times as many males as females. Preliminary 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.