Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

Atsushi Takata, Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Satoko Miyatake, Eriko Koshimizu, Itaru Kushima, Takashi Okada, Mako Morikawa, Yota Uno, Kanako Ishizuka, Kazuhiko Nakamura, Masatsugu Tsujii, Takeo Yoshikawa, Tomoko Toyota, Nobuhiko Okamoto, Yoko Hiraki, Ryota Hashimoto, Yuka Yasuda, Shinji Saitoh & 26 others Kei Ohashi, Yasunari Sakai, Shoichi Ohga, Toshiro Hara, Mitsuhiro Kato, Kazuyuki Nakamura, Aiko Ito, Chizuru Seiwa, Emi Shirahata, Hitoshi Osaka, Ayumi Matsumoto, Saoko Takeshita, Jun Tohyama, Tomoko Saikusa, Toyojiro Matsuishi, Takumi Nakamura, Takashi Tsuboi, Tadafumi Kato, Toshifumi Suzuki, Hirotomo Saitsu, Mitsuko Nakashima, Takeshi Mizuguchi, Fumiaki Tanaka, Norio Mori, Norio Ozaki, Naomichi Matsumoto

研究成果: ジャーナルへの寄稿記事

19 引用 (Scopus)

抄録

Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs. Autism spectrum disorders (ASDs) are genetically heterogeneous neurodevelopmental conditions. Takata et al. analyze de novo mutations (DNMs) in Japanese ASD probands and confirm that the “de novo paradigm” is applicable across cohorts of different ethnicities. They perform integrative analyses of DNMs by combining published datasets, identifying potential disease genes and drug candidates.

元の言語英語
ページ(範囲)734-747
ページ数14
ジャーナルCell Reports
22
発行部数3
DOI
出版物ステータス出版済み - 1 16 2018

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Genes
Mutation
Cardiac Glycosides
Corpus Striatum
Valproic Acid
Bioinformatics
Autism Spectrum Disorder
Computational Biology
Screening
Adenosine Triphosphate
Up-Regulation
Down-Regulation
Networks (circuits)
Gene Expression
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Takata, A., Miyake, N., Tsurusaki, Y., Fukai, R., Miyatake, S., Koshimizu, E., ... Matsumoto, N. (2018). Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder. Cell Reports, 22(3), 734-747. https://doi.org/10.1016/j.celrep.2017.12.074

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder. / Takata, Atsushi; Miyake, Noriko; Tsurusaki, Yoshinori; Fukai, Ryoko; Miyatake, Satoko; Koshimizu, Eriko; Kushima, Itaru; Okada, Takashi; Morikawa, Mako; Uno, Yota; Ishizuka, Kanako; Nakamura, Kazuhiko; Tsujii, Masatsugu; Yoshikawa, Takeo; Toyota, Tomoko; Okamoto, Nobuhiko; Hiraki, Yoko; Hashimoto, Ryota; Yasuda, Yuka; Saitoh, Shinji; Ohashi, Kei; Sakai, Yasunari; Ohga, Shoichi; Hara, Toshiro; Kato, Mitsuhiro; Nakamura, Kazuyuki; Ito, Aiko; Seiwa, Chizuru; Shirahata, Emi; Osaka, Hitoshi; Matsumoto, Ayumi; Takeshita, Saoko; Tohyama, Jun; Saikusa, Tomoko; Matsuishi, Toyojiro; Nakamura, Takumi; Tsuboi, Takashi; Kato, Tadafumi; Suzuki, Toshifumi; Saitsu, Hirotomo; Nakashima, Mitsuko; Mizuguchi, Takeshi; Tanaka, Fumiaki; Mori, Norio; Ozaki, Norio; Matsumoto, Naomichi.

:: Cell Reports, 巻 22, 番号 3, 16.01.2018, p. 734-747.

研究成果: ジャーナルへの寄稿記事

Takata, A, Miyake, N, Tsurusaki, Y, Fukai, R, Miyatake, S, Koshimizu, E, Kushima, I, Okada, T, Morikawa, M, Uno, Y, Ishizuka, K, Nakamura, K, Tsujii, M, Yoshikawa, T, Toyota, T, Okamoto, N, Hiraki, Y, Hashimoto, R, Yasuda, Y, Saitoh, S, Ohashi, K, Sakai, Y, Ohga, S, Hara, T, Kato, M, Nakamura, K, Ito, A, Seiwa, C, Shirahata, E, Osaka, H, Matsumoto, A, Takeshita, S, Tohyama, J, Saikusa, T, Matsuishi, T, Nakamura, T, Tsuboi, T, Kato, T, Suzuki, T, Saitsu, H, Nakashima, M, Mizuguchi, T, Tanaka, F, Mori, N, Ozaki, N & Matsumoto, N 2018, 'Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder', Cell Reports, 巻. 22, 番号 3, pp. 734-747. https://doi.org/10.1016/j.celrep.2017.12.074
Takata, Atsushi ; Miyake, Noriko ; Tsurusaki, Yoshinori ; Fukai, Ryoko ; Miyatake, Satoko ; Koshimizu, Eriko ; Kushima, Itaru ; Okada, Takashi ; Morikawa, Mako ; Uno, Yota ; Ishizuka, Kanako ; Nakamura, Kazuhiko ; Tsujii, Masatsugu ; Yoshikawa, Takeo ; Toyota, Tomoko ; Okamoto, Nobuhiko ; Hiraki, Yoko ; Hashimoto, Ryota ; Yasuda, Yuka ; Saitoh, Shinji ; Ohashi, Kei ; Sakai, Yasunari ; Ohga, Shoichi ; Hara, Toshiro ; Kato, Mitsuhiro ; Nakamura, Kazuyuki ; Ito, Aiko ; Seiwa, Chizuru ; Shirahata, Emi ; Osaka, Hitoshi ; Matsumoto, Ayumi ; Takeshita, Saoko ; Tohyama, Jun ; Saikusa, Tomoko ; Matsuishi, Toyojiro ; Nakamura, Takumi ; Tsuboi, Takashi ; Kato, Tadafumi ; Suzuki, Toshifumi ; Saitsu, Hirotomo ; Nakashima, Mitsuko ; Mizuguchi, Takeshi ; Tanaka, Fumiaki ; Mori, Norio ; Ozaki, Norio ; Matsumoto, Naomichi. / Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder. :: Cell Reports. 2018 ; 巻 22, 番号 3. pp. 734-747.
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abstract = "Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs. Autism spectrum disorders (ASDs) are genetically heterogeneous neurodevelopmental conditions. Takata et al. analyze de novo mutations (DNMs) in Japanese ASD probands and confirm that the “de novo paradigm” is applicable across cohorts of different ethnicities. They perform integrative analyses of DNMs by combining published datasets, identifying potential disease genes and drug candidates.",
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AU - Koshimizu, Eriko

AU - Kushima, Itaru

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AU - Morikawa, Mako

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AU - Ishizuka, Kanako

AU - Nakamura, Kazuhiko

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AU - Kato, Mitsuhiro

AU - Nakamura, Kazuyuki

AU - Ito, Aiko

AU - Seiwa, Chizuru

AU - Shirahata, Emi

AU - Osaka, Hitoshi

AU - Matsumoto, Ayumi

AU - Takeshita, Saoko

AU - Tohyama, Jun

AU - Saikusa, Tomoko

AU - Matsuishi, Toyojiro

AU - Nakamura, Takumi

AU - Tsuboi, Takashi

AU - Kato, Tadafumi

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AU - Mizuguchi, Takeshi

AU - Tanaka, Fumiaki

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