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.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Maekawa
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Toyoshima
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Shimamoto
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hisano
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Shabeesh
authors.initials: S
authors.lastname: Balan
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Fukui, Japan.|Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Takagai
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Complex Systems Science, Graduate School of Information Science, Nagoya University, Nagoya, Japan.
authors.forename: Motonori
authors.initials: M
authors.lastname: Ota
authors.affiliation: Faculty of Engineering, Maebashi Institute of Technology, Maebashi, Gunma, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuchi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.|Department of Neurology, School of Medicine, Aichi Medical University, Aichi, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.|Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.|Faculty of Sociology, Chukyo University, Aichi, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.affiliation: Department of Life Sciences, Toyo University, Gunma, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kojima
authors.affiliation: Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D058953:Neural Stem Cells / Q000378:metabolism; D011487:Protein Conformation; D017422:Sequence Analysis, DNA
chemical_list: D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; C493571:SLC27A4 protein, human