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Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism.
Zhu, Yihui; Gomez, J Antonio; Laufer, Benjamin I; Mordaunt, Charles E; Mouat, Julia S; Soto, Daniela C; Dennis, Megan Y; Benke, Kelly S; Bakulski, Kelly M; Dou, John; Marathe, Ria; Jianu, Julia M; Williams, Logan A; Gutierrez Fugón, Orangel J; Walker, Cheryl K; Ozonoff, Sally; Daniels, Jason; Grosvenor, Luke P; Volk, Heather E; Feinberg, Jason I; Fallin, M Daniele; Hertz-Picciotto, Irva; Schmidt, Rebecca J; Yasui, Dag H; LaSalle, Janine M.
Afiliación
  • Zhu Y; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
  • Gomez JA; Perinatal Origins of Disparities Center, University of California, Davis, CA, USA.
  • Laufer BI; Genome Center, University of California, Davis, CA, USA.
  • Mordaunt CE; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
  • Mouat JS; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
  • Soto DC; Perinatal Origins of Disparities Center, University of California, Davis, CA, USA.
  • Dennis MY; Genome Center, University of California, Davis, CA, USA.
  • Benke KS; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
  • Bakulski KM; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
  • Dou J; Perinatal Origins of Disparities Center, University of California, Davis, CA, USA.
  • Marathe R; Genome Center, University of California, Davis, CA, USA.
  • Jianu JM; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
  • Williams LA; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
  • Gutierrez Fugón OJ; Perinatal Origins of Disparities Center, University of California, Davis, CA, USA.
  • Walker CK; Genome Center, University of California, Davis, CA, USA.
  • Ozonoff S; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
  • Daniels J; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
  • Grosvenor LP; Perinatal Origins of Disparities Center, University of California, Davis, CA, USA.
  • Volk HE; Genome Center, University of California, Davis, CA, USA.
  • Feinberg JI; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
  • Fallin MD; Genome Center, University of California, Davis, CA, USA.
  • Hertz-Picciotto I; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
  • Schmidt RJ; Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, USA.
  • Yasui DH; Genome Center, University of California, Davis, CA, USA.
  • LaSalle JM; MIND Institute, School of Medicine, University of California, Davis, CA, USA.
Genome Biol ; 23(1): 46, 2022 02 16.
Article en En | MEDLINE | ID: mdl-35168652
ABSTRACT

BACKGROUND:

Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome.

RESULTS:

We use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence.

CONCLUSIONS:

Together, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trastorno Autístico / Trastorno del Espectro Autista Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Newborn / Pregnancy Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trastorno Autístico / Trastorno del Espectro Autista Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Newborn / Pregnancy Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos