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Hill, Robert

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Hill

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Robert

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Hill, Robert

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2012 - 20173

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Author's Publications: search.filters.isAuthorOfPublication.acd30c8c-1487-45b4-af5e-c39ad329fbbe

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Now showing 1 - 3 of 3
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    Rates, Distribution, and Implications of Post-zygotic Mosaic Mutations in Autism Spectrum Disorder
    (2017) Lim, Elaine T.; Uddin, Mohammed; De Rubeis, Silvia; Chan, Yingleong; Kamumbu, Anne S.; Zhang, Xiaochang; D'Gama, Alissa; Kim, Sonia; Hill, Robert; Goldberg, Arthur P.; Poultney, Christopher; Minshew, Nancy J.; Kushima, Itaru; Aleksic, Branko; Ozaki, Norio; Parellada, Mara; Arango, Celso; Penzol, Maria J.; Carracedo, Angel; Kolevzon, Alexander; Hultman, Christina M.; Weiss, Lauren A.; Fromer, Menachem; Chiocchetti, Andreas G.; Freitag, Christine M.; Church, George; Scherer, Stephen W.; Buxbaum, Joseph D.; Walsh, Christopher
    We systematically analyzed post-zygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed re-sequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, with 83.3% of these PZMs not discovered in previous studies. Damaging, non-synonymous PZMs within critical exons of prenatally-expressed genes were more common in ASD probands than controls (P<1×10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P=5.4×10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU, SMARCA4) known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.
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    CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development
    (2013) Mochida, Ganeshwaran; Ganesh, Vijay; de Michelena, Maria I.; Dias, Hugo; Atabay, Kutay D.; Kathrein, Katie L.; Huang, Emily; Hill, Robert; Felie, Jillian M.; Rakiec, Daniel; Gleason, Danielle; Hill, Anthony D.; Malik, Athar; Barry, Brenda J.; Partlow, Jennifer; Tan, Wen-Hann; Glader, Laurie; Barkovich, A. James; Dobyns, William B.; Zon, Leonard; Walsh, Christopher
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    Whole-Exome Sequencing and Homozygosity Analysis Implicate Depolarization-Regulated Neuronal Genes in Autism
    (Public Library of Science, 2012) Yu, Timothy W.; Lim, Elaine T.; Stevens, Christine R.; Gabriel, Stacey B.; Chahrour, Maria H.; Ataman, Bulent; Coulter, Michael Edward; Hill, Robert; Schubert, Christian; Greenberg, Michael; Walsh, Christopher
    Although autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing of 16 probands revealed validated homozygous, potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode proteins involved in proteolysis, GTPase-mediated signaling, cytoskeletal organization, and other pathways. Furthermore, neuronal depolarization regulated the transcription of these genes, suggesting potential activity-dependent roles in neurons. We present a multidimensional strategy for filtering whole-exome sequence data to find candidate recessive mutations in autism, which may have broader applicability to other complex, heterogeneous disorders.