Premium
Genetic analyses of Roundabout ( ROBO ) axon guidance receptors in autism
Author(s) -
Anitha A.,
Nakamura Kazuhiko,
Yamada Kazuo,
Suda Shiro,
Thanseem Ismail,
Tsujii Masatsugu,
Iwayama Yoshimi,
Hattori Eiji,
Toyota Tomoko,
Miyachi Taishi,
Iwata Yasuhide,
Suzuki Katsuaki,
Matsuzaki Hideo,
Kawai Masayoshi,
Sekine Yoshimoto,
Tsuchiya Kenji,
Sugihara Genichi,
Ouchi Yasuomi,
Sugiyama Toshiro,
Koizumi Keita,
Higashida Haruhiro,
Takei Nori,
Yoshikawa Takeo,
Mori Norio
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30697
Subject(s) - autism , serotonergic , serotonin transporter , axon guidance , neuroscience , biology , psychology , serotonin , genetics , receptor , axon , psychiatry
Autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (SERT) modulates serotonin levels, and is a major therapeutic target in autism. Factors that regulate SERT expression might be implicated in the pathophysiology of autism. One candidate SERT regulatory protein is the roundabout axon guidance molecule, ROBO. SerT expression in Drosophila is regulated by robo ; it plays a vital role in mammalian neurodevelopment also. Here, we examined the associations of ROBO3 and ROBO4 with autism, in a trio association study using DNA from 252 families recruited to AGRE. Four SNPs of ROBO3 (rs3923890, P = 0.023; rs7925879, P = 0.017; rs4606490, P = 0.033; and rs3802905, P = 0.049) and a single SNP of ROBO4 (rs6590109, P = 0.009) showed associations with autism; the A/A genotype of rs3923890 showed lower ADI‐R_A scores, which reflect social interaction. Significant haplotype associations were also observed for ROBO3 and ROBO4 . We further compared the mRNA expressions of ROBO1 , ROBO2 , ROBO3 , and ROBO4 in the lymphocytes of 19 drug‐naïve autistic patients and 20 age‐ and sex‐matched controls. Expressions of ROBO1 ( P = 0.018) and ROBO2 ( P = 0.023) were significantly reduced in the autistic group; the possibility of using the altered expressions of ROBO as peripheral markers for autism, may be explored. In conclusion, we suggest a possible role of ROBO in the pathogenesis of autism. Abnormalities of ROBO may lead to autism either by interfering with serotonergic system, or by disrupting neurodevelopment. To the best of our knowledge, this is the first report relating ROBO with autism. © 2008 Wiley‐Liss, Inc.