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Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals
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 bee...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785550/ https://www.ncbi.nlm.nih.gov/pubmed/27081536 http://dx.doi.org/10.1038/hgv.2015.24 |
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author | Liu, Xiaoxi Kawashima, Minae Miyagawa, Taku Otowa, Takeshi Latt, Khun Zaw Thiri, Myo Nishida, Hisami Sugiyama, Toshiro Tsurusaki, Yoshinori Matsumoto, Naomichi Mabuchi, Akihiko Tokunaga, Katsushi Sasaki, Tsukasa |
author_facet | Liu, Xiaoxi Kawashima, Minae Miyagawa, Taku Otowa, Takeshi Latt, Khun Zaw Thiri, Myo Nishida, Hisami Sugiyama, Toshiro Tsurusaki, Yoshinori Matsumoto, Naomichi Mabuchi, Akihiko Tokunaga, Katsushi Sasaki, Tsukasa |
author_sort | Liu, Xiaoxi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4785550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47855502016-04-14 Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals Liu, Xiaoxi Kawashima, Minae Miyagawa, Taku Otowa, Takeshi Latt, Khun Zaw Thiri, Myo Nishida, Hisami Sugiyama, Toshiro Tsurusaki, Yoshinori Matsumoto, Naomichi Mabuchi, Akihiko Tokunaga, Katsushi Sasaki, Tsukasa Hum Genome Var Article 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. Nature Publishing Group 2015-07-30 /pmc/articles/PMC4785550/ /pubmed/27081536 http://dx.doi.org/10.1038/hgv.2015.24 Text en Copyright © 2015 The Japan Society of Human Genetics http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Liu, Xiaoxi Kawashima, Minae Miyagawa, Taku Otowa, Takeshi Latt, Khun Zaw Thiri, Myo Nishida, Hisami Sugiyama, Toshiro Tsurusaki, Yoshinori Matsumoto, Naomichi Mabuchi, Akihiko Tokunaga, Katsushi Sasaki, Tsukasa Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals |
title | Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals |
title_full | Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals |
title_fullStr | Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals |
title_full_unstemmed | Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals |
title_short | Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals |
title_sort | novel rare variations of the oxytocin receptor (oxtr) gene in autism spectrum disorder individuals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785550/ https://www.ncbi.nlm.nih.gov/pubmed/27081536 http://dx.doi.org/10.1038/hgv.2015.24 |
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