Photo of Brian O'Roak, Ph.D.

Brian O'Roak Ph.D.

    • Associate Professor of Molecular and Medical Genetics School of Medicine
    • Molecular and Medical Genetics Graduate Program School of Medicine
    • Neuroscience Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

I’m originally from California’s Central Valley. After earning a B.S. in Biology at CSU Fresno, I did my PhD studies at Yale University working with Dr. Matthew W. State in the Department of Genetics. I then went on for postdoctoral training in the Department of Genome Sciences at the University of Washington, under Drs. Evan E. Eichler and Jay Shendure. I joined the MMG faculty in Fall 2013.

My goal is to understand the molecular basis of neurodevelopmental disorders (NDDs) and have these fundamental insights translate into meaningful clinical interventions. My pioneering work in the last decade has focused on developing and implementing new research paradigms and technologies that challenge the genetic intractability of complex NDDs, especially autism spectrum disorder (ASD). Through these studies, and similar efforts by others, ~100 different genes are no longer merely ‘candidate’ genes for ASD risk, but are now ‘known’ genes based on their recurrent disruption by de novo mutations.

Defining the molecular mechanisms that underlie autism requires not only identification of critical genetic risk factors, but also understanding how they interact within a complex and developing system. In addition to our gene discovery efforts, our lab is now building a new paradigm that incorporates many different patient-specific mutations in a multitude of models with complementary strengths and weaknesses. Advances in genome editing, induced pluripotent stem cells (iPSCs), neurogenetics, and functional genomics have made this patient-specific approach feasible. Furthermore, we are focusing on mutations in genes that are master regulators of key biologic networks provides an avenue for reducing the phenotypic complexity of autism, biomarker discovery, and targeted personalized therapies that will have impact beyond a single risk gene.

Read more

Areas of interest

  • Autism
  • Neurodevelopmental disorders
  • Genetics/genomics
  • Stem cells
  • Developmental neuroscience


  • Ph.D., Yale University 2009

Memberships and associations

  • American Society of Human Genetics
  • Society for Neuroscience


  • "Copy number variation detection and genotyping from exome sequence data" PCR Methods and Applications August 2012
  • "GABRA1 and STXBP1" Neurology April 8 2014
  • "The contribution of de novo coding mutations to autism spectrum disorder" Nature November 13 2014
  • "A general framework for estimating the relative pathogenicity of human genetic variants" Nature Genetics  2014
  • "GRIN2A mutations cause epilepsy-aphasia spectrum disorders" Nature Genetics September 2013
  • "Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma" PLoS One August 12 2014
  • "Additional support for the association of SLITRK1 var321 and Tourette syndrome" Molecular Psychiatry May 2010
  • "Rare independent mutations in renal salt handling genes contribute to blood pressure variation" Nature Genetics May 2008
  • "Challenges and solutions for gene identification in the presence of familial locus heterogeneity" European Journal of Human Genetics September 14 2015
  • "Joubert syndrome" Journal of Medical Genetics  2015
  • "Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations" Nature Genetics June 2011
  • "Erratum" American Journal of Human Genetics February 6 2014
  • "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes" Nature Genetics August 2012
  • "Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism" Neuron June 9 2011
  • "Mutations in CSPP1 cause primary cilia abnormalities and joubert syndrome with or without Jeune asphyxiating thoracic dystrophy" American Journal of Human Genetics January 2 2014
  • "Disruptive CHD8 mutations define a subtype of autism early in development" Cell July 17 2014
  • "De novo TBR1 mutations in sporadic autism disrupt protein functions" Nature Communications  2014
  • "A de novo convergence of autism genetics and molecular neuroscience" Trends in Neurosciences February 2014
  • "Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3" Neurosurgery November 2005
  • "Detection of structural variants and indels within exome data" PLoS Medicine February 2012
  • "Recurrent de novo mutations implicate novel genes underlying simplex autism risk" Nature Communications  2014
  • "Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders" Science December 21 2012
  • "Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders" American Journal of Human Genetics January 10 2008
  • "Autism genetics" Autism Research  2008
  • "Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions" PLoS Medicine September 2013
  • "Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1" Nature Genetics July 2013
  • "Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation" PCR Methods and Applications May 2013
  • "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome" Nature Genetics April 2012
  • "Estimating the human mutation rate using autozygosity in a founder population" Nature Genetics November 2012
  • "L-histidine decarboxylase and Tourette's syndrome" New England Journal of Medicine May 20 2010

Additional information

Edit profile