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.

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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


  • "Highly scalable generation of DNA methylation profiles in single cells." Nature Biotechnology  In: , Vol. 36, No. 5, 01.06.2018, p. 428-431.
  • "A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships." American Journal of Human Genetics  In: , Vol. 102, No. 5, 03.05.2018, p. 943-955.
  • "SPARK : A US Cohort of 50,000 Families to Accelerate Autism Research." Neuron  In: , Vol. 97, No. 3, 07.02.2018, p. 488-493.
  • "Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder." American Journal of Human Genetics  In: , 2017.
  • "Current perspectives in autism spectrum disorder : From genes to therapy." Journal of Neuroscience  In: , Vol. 36, No. 45, 09.11.2016, p. 11402-11410.
  • "Large-scale targeted sequencing comparison highlights extreme genetic heterogeneity in nephronophthisis-related ciliopathies." Journal of Medical Genetics  In: , Vol. 53, No. 3, 2016, p. 208-214.
  • "Challenges and solutions for gene identification in the presence of familial locus heterogeneity." European Journal of Human Genetics  In: , Vol. 23, No. 9, 14.09.2015, p. 1207-1215.
  • "Genotype-Phenotype correlations in Joubert Syndrome in the Era of Next Generation Sequencing." Cilia  In: , No. SUPPLEMENT 1, P8, 13.07.2015.
  • "Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos." Journal of Allergy and Clinical Immunology  In: , Vol. 135, No. 6, 01.06.2015, p. 1502-1510.
  • "PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia." Brain  In: , Vol. 138, No. 6, 01.06.2015, p. 1613-1628.
  • "Joubert syndrome : A model for untangling recessive disorders with extreme genetic heterogeneity." Journal of Medical Genetics  In: , Vol. 52, No. 8, 2015, p. 514-522.
  • "Mutations and modeling of the chromatin remodeler CHD8 define an emerging autism etiology." Frontiers in Neuroscience  In: , Vol. 9, No. DEC, 00477, 2015.
  • "The contribution of de novo coding mutations to autism spectrum disorder." Nature  In: , Vol. 515, No. 7526, 13.11.2014, p. 216-221.
  • "Refining analyses of copy number variation identifies specific genes associated with developmental delay." Nature Genetics  In: , Vol. 46, No. 10, 26.09.2014, p. 1063-1071.
  • "Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma." PLoS One  In: , Vol. 9, No. 8, e104396, 12.08.2014.
  • "Disruptive CHD8 mutations define a subtype of autism early in development." Cell  In: , Vol. 158, No. 2, 17.07.2014, p. 263-276.
  • "GABRA1 and STXBP1 : Novel genetic causes of Dravet syndrome." Neurology  In: , Vol. 82, No. 14, 08.04.2014, p. 1245-1253.
  • "Erratum : Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without jeune asphyxiating thoracic dystrophy (American Journal of Human Genetics (2014) 94 (62-72))." American Journal of Human Genetics  In: , Vol. 94, No. 2, 06.02.2014, p. 310.
  • "A de novo convergence of autism genetics and molecular neuroscience." Trends in Neurosciences  In: , Vol. 37, No. 2, 02.2014, p. 95-105.
  • "Mutations in CSPP1 cause primary cilia abnormalities and joubert syndrome with or without Jeune asphyxiating thoracic dystrophy." American Journal of Human Genetics  In: , Vol. 94, No. 1, 02.01.2014, p. 62-72.
  • "Rare-variant extensions of the transmission disequilibrium test : Application to autism exome sequence data." American Journal of Human Genetics  In: , Vol. 94, No. 1, 02.01.2014, p. 33-46.
  • "A general framework for estimating the relative pathogenicity of human genetic variants." Nature Genetics  In: , Vol. 46, No. 3, 2014, p. 310-315.
  • "De novo TBR1 mutations in sporadic autism disrupt protein functions." Nature Communications  In: , Vol. 5, 4954, 2014.
  • "Recurrent de novo mutations implicate novel genes underlying simplex autism risk." Nature Communications  In: , Vol. 5, 5595, 2014.
  • "MIPgen : Optimized modeling and design of molecular inversion probes for targeted resequencing." Bioinformatics  In: , Vol. 30, No. 18, 2014, p. 2670-2672.
  • "Transmission disequilibrium of small CNVs in simplex autism." American Journal of Human Genetics  In: , Vol. 93, No. 4, 03.10.2013, p. 595-606.
  • "GRIN2A mutations cause epilepsy-aphasia spectrum disorders." Nature Genetics  In: , Vol. 45, No. 9, 09.2013, p. 1073-1076.
  • "Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions." Nature Methods  In: , Vol. 10, No. 9, 09.2013, p. 903-909.
  • "Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1." Nature Genetics  In: , Vol. 45, No. 7, 07.2013, p. 825-830.
  • "Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation." Genome Research  In: , Vol. 23, No. 5, 05.2013, p. 843-854.

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