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Transcriptomic analysis of autistic brain reveals convergent molecular pathology

Author

Listed:
  • Irina Voineagu

    (Program in Neurogenetics and Neurobehavioral Genetics, David Geffen School of Medicine, University of California)

  • Xinchen Wang

    (Donnelly Centre, University of Toronto, Toronto, Ontario M5G 1L6, Canada)

  • Patrick Johnston

    (Institute of Psychiatry, King’s College London, London SE5 8AF, UK)

  • Jennifer K. Lowe

    (Program in Neurogenetics and Neurobehavioral Genetics, David Geffen School of Medicine, University of California)

  • Yuan Tian

    (Program in Neurogenetics and Neurobehavioral Genetics, David Geffen School of Medicine, University of California)

  • Steve Horvath

    (University of California Los Angeles)

  • Jonathan Mill

    (Institute of Psychiatry, King’s College London, London SE5 8AF, UK)

  • Rita M. Cantor

    (University of California Los Angeles)

  • Benjamin J. Blencowe

    (Donnelly Centre, University of Toronto, Toronto, Ontario M5G 1L6, Canada)

  • Daniel H. Geschwind

    (Program in Neurogenetics and Neurobehavioral Genetics, David Geffen School of Medicine, University of California
    University of California Los Angeles)

Abstract

A shared aetiology for autism? Despite high heritability, autism is genetically very heterogeneous. This raises the question of whether there are many different pathologies presenting as autistic spectrum disorder (ASD), or whether the myriad genetic causes converge on a few biological pathways affected in most individuals, which could be therapeutically targeted. A study using transcriptome and gene co-expression network analysis suggests that the latter, convergent model is the case. The gene expression patterns that typically distinguish frontal and temporal cortex are much less pronounced in the ASD brain, and specific splicing abnormalities and modules of co-expressed genes associated with autism are enriched for previously identified genetic association signals. This points to transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.

Suggested Citation

  • Irina Voineagu & Xinchen Wang & Patrick Johnston & Jennifer K. Lowe & Yuan Tian & Steve Horvath & Jonathan Mill & Rita M. Cantor & Benjamin J. Blencowe & Daniel H. Geschwind, 2011. "Transcriptomic analysis of autistic brain reveals convergent molecular pathology," Nature, Nature, vol. 474(7351), pages 380-384, June.
    • Handle: RePEc:nat:nature:v:474:y:2011:i:7351:d:10.1038_nature10110
    DOI: 10.1038/nature10110
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    Cited by:

    1. Tetsushi Sadakata & Yo Shinoda & Akira Sato & Hirotoshi Iguchi & Chiaki Ishii & Makoto Matsuo & Ryosuke Yamaga & Teiichi Furuichi, 2013. "Mouse Models of Mutations and Variations in Autism Spectrum Disorder-Associated Genes: Mice Expressing Caps2/Cadps2 Copy Number and Alternative Splicing Variants," IJERPH, MDPI, vol. 10(12), pages 1-19, November.
    2. Sek Won Kong & Christin D Collins & Yuko Shimizu-Motohashi & Ingrid A Holm & Malcolm G Campbell & In-Hee Lee & Stephanie J Brewster & Ellen Hanson & Heather K Harris & Kathryn R Lowe & Adrianna Saada , 2012. "Characteristics and Predictive Value of Blood Transcriptome Signature in Males with Autism Spectrum Disorders," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-13, December.
    3. Tanzil Rujeedawa & Shahid H. Zaman, 2022. "The Diagnosis and Management of Autism Spectrum Disorder (ASD) in Adult Females in the Presence or Absence of an Intellectual Disability," IJERPH, MDPI, vol. 19(3), pages 1-13, January.
    4. Luye Qin & Jamal B. Williams & Tao Tan & Tiaotiao Liu & Qing Cao & Kaijie Ma & Zhen Yan, 2021. "Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    5. Yudong Gao & Daichi Shonai & Matthew Trn & Jieqing Zhao & Erik J. Soderblom & S. Alexandra Garcia-Moreno & Charles A. Gersbach & William C. Wetsel & Geraldine Dawson & Dmitry Velmeshev & Yong-hui Jian, 2024. "Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Hyoseon Oh & Suho Lee & Yusang Oh & Seongbin Kim & Young Seo Kim & Yeji Yang & Woochul Choi & Ye-Eun Yoo & Heejin Cho & Seungjoon Lee & Esther Yang & Wuhyun Koh & Woojin Won & Ryunhee Kim & C. Justin , 2023. "Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Benjamin A Samuels & E David Leonardo & Alex Dranovsky & Amanda Williams & Erik Wong & Addie May I Nesbitt & Richard D McCurdy & Rene Hen & Mark Alter, 2014. "Global State Measures of the Dentate Gyrus Gene Expression System Predict Antidepressant-Sensitive Behaviors," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-10, January.
    8. Stefano Berto & Alex H. Treacher & Emre Caglayan & Danni Luo & Jillian R. Haney & Michael J. Gandal & Daniel H. Geschwind & Albert A. Montillo & Genevieve Konopka, 2022. "Association between resting-state functional brain connectivity and gene expression is altered in autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Leif Ekblad, 2013. "Autism, Personality, and Human Diversity," SAGE Open, , vol. 3(3), pages 21582440134, August.
    10. Iva Salamon & Yongkyu Park & Terezija Miškić & Janja Kopić & Paul Matteson & Nicholas F. Page & Alfonso Roque & Geoffrey W. McAuliffe & John Favate & Marta Garcia-Forn & Premal Shah & Miloš Judaš & Ja, 2023. "Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    11. Glenn N Saxe & Alexander Statnikov & David Fenyo & Jiwen Ren & Zhiguo Li & Meera Prasad & Dennis Wall & Nora Bergman & Ernestine C Briggs & Constantin Aliferis, 2016. "A Complex Systems Approach to Causal Discovery in Psychiatry," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-20, March.
    12. Yang Shi & Hui Jiang, 2013. "rSeqDiff: Detecting Differential Isoform Expression from RNA-Seq Data Using Hierarchical Likelihood Ratio Test," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-11, November.
    13. Alexandros A. Lavdas & Nikos A. Salingaros, 2021. "Can Suboptimal Visual Environments Negatively Affect Children’s Cognitive Development?," Challenges, MDPI, vol. 12(2), pages 1-12, November.
    14. Takeshi Kaizuka & Takehiro Suzuki & Noriyuki Kishi & Kota Tamada & Manfred W. Kilimann & Takehiko Ueyama & Masahiko Watanabe & Tomomi Shimogori & Hideyuki Okano & Naoshi Dohmae & Toru Takumi, 2024. "Remodeling of the postsynaptic proteome in male mice and marmosets during synapse development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Hyosang Kim & Doyoun Kim & Yisul Cho & Kyungdeok Kim & Junyeop Daniel Roh & Yangsik Kim & Esther Yang & Seong Soon Kim & Sunjoo Ahn & Hyun Kim & Hyojin Kang & Yongchul Bae & Eunjoon Kim, 2022. "Early postnatal serotonin modulation prevents adult-stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Idan Menashe & Pascal Grange & Eric C Larsen & Sharmila Banerjee-Basu & Partha P Mitra, 2013. "Co-expression Profiling of Autism Genes in the Mouse Brain," PLOS Computational Biology, Public Library of Science, vol. 9(7), pages 1-10, July.

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