Genetic analyses of Roundabout (ROBO) axon guidance receptors in autism

Medientyp: E-Artikel
Titel: Genetic analyses of Roundabout (ROBO) axon guidance receptors in autism
Beteiligte: 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, Gen‐ichi; Ouchi, Yasuomi; Sugiyama, Toshiro; Koizumi, Keita; Higashida, Haruhiro; Takei, Nori; Yoshikawa, Takeo; Mori, Norio
Erschienen: Wiley, 2008
Erschienen in: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Sprache: Englisch
DOI: 10.1002/ajmg.b.30697
ISSN: 1552-4841; 1552-485X
Schlagwörter: Cellular and Molecular Neuroscience ; Psychiatry and Mental health ; Genetics (clinical)
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Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Drosophila</jats:italic> is regulated by <jats:italic>robo</jats:italic>; it plays a vital role in mammalian neurodevelopment also. Here, we examined the associations of <jats:italic>ROBO3</jats:italic> and <jats:italic>ROBO4</jats:italic> with autism, in a trio association study using DNA from 252 families recruited to AGRE. Four SNPs of <jats:italic>ROBO3</jats:italic> (rs3923890, <jats:italic>P</jats:italic> = 0.023; rs7925879, <jats:italic>P</jats:italic> = 0.017; rs4606490, <jats:italic>P</jats:italic> = 0.033; and rs3802905, <jats:italic>P</jats:italic> = 0.049) and a single SNP of <jats:italic>ROBO4</jats:italic> (rs6590109, <jats:italic>P</jats:italic> = 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 <jats:italic>ROBO3</jats:italic> and <jats:italic>ROBO4</jats:italic>. We further compared the mRNA expressions of <jats:italic>ROBO1</jats:italic>, <jats:italic>ROBO2</jats:italic>, <jats:italic>ROBO3</jats:italic>, and <jats:italic>ROBO4</jats:italic> in the lymphocytes of 19 drug‐naïve autistic patients and 20 age‐ and sex‐matched controls. Expressions of <jats:italic>ROBO1</jats:italic> (<jats:italic>P</jats:italic> = 0.018) and <jats:italic>ROBO2</jats:italic> (<jats:italic>P</jats:italic> = 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.</jats:p>

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