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Sci Rep. 2015 Nov 9;5:16239. doi: 10.1038/srep16239.

Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism.

Author information

1
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
2
Research Center for Child Mental Development, University of Fukui, Fukui, Japan.
3
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
4
Department of Complex Systems Science, Graduate School of Information Science, Nagoya University, Nagoya, Japan.
5
Faculty of Engineering, Maebashi Institute of Technology, Maebashi, Gunma, Japan.
6
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
7
Department of Neurology, School of Medicine, Aichi Medical University, Aichi, Japan.
8
Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo, Japan.
9
Faculty of Sociology, Chukyo University, Aichi, Japan.
10
Department of Life Sciences, Toyo University, Gunma, Japan.
11
Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

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.

PMID:
26548558
PMCID:
PMC4637822
DOI:
10.1038/srep16239
[Indexed for MEDLINE]
Free PMC Article

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