title: Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals.
abstract: The oxytocin receptor (OXTR) gene has been implicated as a risk gene for autism spectrum disorder (ASD)-a neurodevelopmental disorder with essential features of impairments in social communication and reciprocal interaction. The genetic associations between common variations in OXTR and ASD have been reported in multiple ethnic populations. However, little is known about the distribution of rare variations within OXTR in ASD patients. In this study, we resequenced the full length of OXTR in 105 ASD individuals using an approach that combined the power of next-generation sequencing technology, long-range PCR and DNA pooling. We demonstrated that rare variants with minor allele frequency as low as 0.05% could be reliably detected by our method. We identified 28 novel variants including potential functional variants in the intron region and one rare missense variant (R150S). We subsequently performed Sanger sequencing and validated five novel variants located in previously suggested candidate regions in ASD individuals. Further sequencing of 312 healthy subjects showed that the burden of rare variants is significantly higher in ASDs compared with healthy individuals. Our results support that the rare variation in OXTR gene might be involved in ASD.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Minae
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Miyagawa
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otowa
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Khun Zaw
authors.initials: KZ
authors.lastname: Latt
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Myo
authors.initials: M
authors.lastname: Thiri
authors.affiliation: Asunaro Hospital for Child and Adolescent Psychiatry , Tsu, Japan.
authors.forename: Hisami
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine , Hamamatsu, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University , Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, Yokohama City University , Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Mabuchi
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo , Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Physical and Health Education, Graduate School of Education, The University of Tokyo , Tokyo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki