Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis.
Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis.
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DOI：
10.1371/journal.pone.0005775
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发表时间：
2009-06-03
期刊：
影响因子：
3.7
通讯作者：
Lee NH
中科院分区：
文献类型：
--
作者：
Hu VW;Nguyen A;Kim KS;Steinberg ME;Sarachana T;Scully MA;Soldin SJ;Luu T;Lee NH
尽管许多自闭症易感基因的鉴定，自闭症的病理生物学仍然未知。目前的“病例对照”研究采取了一种全球性的方法，以了解自闭症谱系障碍的分子基础上大规模的基因表达谱。对来自20对同胞的淋巴母细胞系进行DNA微阵列分析，其中一个同胞被诊断为自闭症，另一个未受影响，以鉴定自闭症和非自闭症同胞细胞中差异调节的生化和信号通路。数据的生物信息学和基因本体论分析涉及参与神经系统发育、炎症和细胞骨架组织的基因，以及可能与通常与自闭症相关的胃肠道或其他生理症状相关的基因。此外，这些数据进一步表明，这些过程可能是由胆固醇/类固醇代谢，特别是在雄激素水平的调节。反过来，男性荷尔蒙的升高被认为是影响自闭症易感性的一个可能因素，自闭症影响的男性是女性的2.4倍。从几对兄弟姐妹的淋巴母细胞系中的类固醇激素的初步代谢谱揭示了自闭症兄弟姐妹中较高水平的睾酮，这与类固醇生成途径中涉及的两个基因的表达增加一致。因此，ASD先证者培养细胞的全球基因表达谱可以作为潜在代谢和信号转导缺陷的窗口，这些缺陷可能与自闭症的病理生物学有关。
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. 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.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
DOI：
10.1016/j.pathophys.2006.05.007
发表时间：
2006-08-01
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Chauhan, Abha;Chauhan, Ved
通讯作者：
Chauhan, Ved
影响因子：
3.9
作者：
GARNIER, C;COMOY, E;LELORD, G
通讯作者：
LELORD, G
影响因子：
11.2
作者：
Campbell, Daniel B.;D'Oronzio, Rosanna;Persico, Antonio M.
通讯作者：
Persico, Antonio M.