The Talkowski Laboratory studies the genetic etiology of complex neurodevelopmental and neuropsychiatric disorders. We incorporate the development of molecular, bioinformatic, and statistical methods to delineate strong effect mutations in the human genome and to characterize their consequences at the level of individual genes, pathways, and phenotypic outcomes. We are also interested in technical innovations that will benefit both prenatal and postnatal genetic diagnostics.  Our recent studies have identified novel genes associated with autism spectrum disorders as well as other neurodevelopmental loci, individual gene contributions to previously known microdeletion and duplication syndromes, the complex landscape of chromosomal rearrangements and the phenomenon of germline chromothripsis, and a the first prenatal diagnostic application of whole-genome sequencing by large-insert libraries.  The group is funded by resources from the National Institutes of Health, the Simons Foundation for Autism Research, the Nancy Lurie Marks Family Foundation, the Charles Hood Foundation, the March of Dimes, and NARSAD.

Research Highlights

Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk Across Diagnostic Boundaries. Talkowski et. al. Cell. 2012 Apr 27;149(3):525-37 PMID:22521361

Complex Reorganization Predominant Non Homologous Repair Following Chromosomal Breakage in Karyotypically Balanced Germline Rearrangements and Transgenic Animals. Chiang et. al. Nat Genet. 2012 Mar 4:44(4):390-7. PMID:22388000.

Balanced Germline Chromothripsis


Transgene Architecture

Mechanism of Formation – Predominant Nonhomologous Repair

Clinical Diagnosis by Whole-Genome Sequencing of a Prenatal Sample. Talkowski et. al. N Engl J Med. 2012 Dec 6;367(23):2226-32. PMID:232155558



Assessment of 2q23.1 Microdeletion Syndrome Implicates MBD5 as a Single Causal Locus of Intellectual Disability, Epilepsy, and Autism Spectrum Disorder. Talkowski et. al. Am J Hum Genet. 2011 Oct 7;89(4):551-63. PMID:21981781