@article{2e90e6964a984e7ea2a3d4b59f717c16,
title = "Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism",
abstract = "The solute carrier 27A (SLC27A) gene family encodes fatty acid transport proteins (FATPs) and includes 6 members. During fetal and postnatal periods of development, the growing brain requires a reliable supply of fatty acids. Because autism spectrum disorders (ASD) are now recognized as disorders caused by impaired early brain development, it is possible that functional abnormalities of SLC27A genes may contribute to the pathogenesis of ASD. Here, we confirmed the expression of SLC27A3 and SLC27A4 in human neural stem cells derived from human induced pluripotent stem cells, which suggested their involvement in the developmental stage of the central nervous system. Additionally, we resequenced the SLC27A3 and SLC27A4 genes using 267 ASD patient and 1140 control samples and detected 47 (44 novel and 29 nonsynonymous) and 30 (17 novel and 14 nonsynonymous) variants for the SLC27A3 and SLC27A4, respectively, revealing that they are highly polymorphic with multiple rare variants. The SLC27A4 Ser209 allele was more frequently represented in ASD samples. Furthermore, we showed that a SLC27A4 Ser209 mutant resulted in significantly higher fluorescently-labeled fatty acid uptake into bEnd3 cells, a mouse brain capillary-derived endothelial cell line, compared with SLC27A4 Gly209, suggesting that the functional change may contribute to ASD pathophysiology.",
author = "Motoko Maekawa and Yoshimi Iwayama and Tetsuo Ohnishi and Manabu Toyoshima and Chie Shimamoto and Yasuko Hisano and Tomoko Toyota and Shabeesh Balan and Hideo Matsuzaki and Yasuhide Iwata and Shu Takagai and Kohei Yamada and Motonori Ota and Satoshi Fukuchi and Yohei Okada and Wado Akamatsu and Masatsugu Tsujii and Nobuhiko Kojima and Yuji Owada and Hideyuki Okano and Norio Mori and Takeo Yoshikawa",
note = "Funding Information: We thank Dr. Naruya Saito (Division of Population Genetics, National Institute of Genetics, Mishima, Japan) for helpful discussions, Dr. Kazuo Yamada (RIKEN Brain Science Institute, Saitama, Japan) for his help with statistical analysis, and Dr. Kenji J Tsuchiya (Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan) for his help with clinical evaluations. We also thank the Research Resource Center of the RIKEN Brain Science Institute (BSI) for sequencing support. This study was supported, in part, by grants-in-aid for Scientific Research and by a grant-in-aid for Scientific Research on Innovative Areas (TY) from the Japan Society for the Promotion of Science (JSPS), Japan. This study was also supported by RIKEN Brain Science Institute Funds (TY), and a part of this study was the result of the “Development of Biomarker Candidates for Social Behavior” (TY) and “Integrated Research on Neuropsychiatric Disorders” (NM) projects, carried out under the Strategic Research Program for Brain Sciences, and a grant “Platform for Drug Discovery, Informatics, and Structural Life Science” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and Japan Agency for Medical Research and development (AMED) (MO and SF). This study was also supported by grants from the Mitsubishi Pharma Research Foundation (MM) and by the Program for Intractable Disease Research Utilizing Disease-specific iPS Cells funded by the Japan Science and Technology Agency (JST) and MEXT to HO.",
year = "2015",
month = nov,
day = "9",
doi = "10.1038/srep16239",
language = "English",
volume = "5",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}