The Geschwind Lab uses genetic techniques ranging from genotyping of polymorphic markers to whole exome and whole genome sequencing (WGS) to identify genes associated with neuropsychiatric disorders, focusing on autism spectrum disorders (ASD) and neurodegenerative disorders such as Frontotemporal Dementia (FTD) and Progressive Supranuclear Palsy (PSP).
Some genetic variants sit within regions such as protein coding regions (exomes), whose functional consequences can be readily assigned to a specific gene. However, most genetic variation associated with disease sits outside of known protein coding regions in regions that are presumed to be regulatory. Although one convention is to assign these regions to the closest gene, in many cases, there is mounting evidence that these regions do not regulate the closest gene, but rather act at a distance. Moreover, although about half of regulatory relationships occur across tissues, the remaining relationships are either tissue or development stage restricted.
In Autism Spectrum Disorders
We are engaged in two major studies to expand our knowledge of genetic risk factors for ASD. The first study is a multi-site study to define common and rare genetic risk for ASD in African Americans, a traditionally underrepresented population in genetic studies (NIH RePORTER)
. The second major study involves WGS in approximately 1,000 families from the Autism Genetic Resource Exchange to identify additional risk variants and genes as part of the iHART
project. We are investigating coding and noncoding variants, as well as structural variation.
In Neurodegenerative Disorders
We are moving toward developing precision medicine for neurologic and psychiatric patients. We serve as the genetics core for the UCSF Memory and Aging Center
in connection with the Coppola Lab
. As part of our work on FTD and PSP, we are performing WGS to identify new genetic risk factors in large cohorts.
Gandal et al.
2016, The road to precision psychiatry: translating genetics into disease mechanisms
, Nat Neurosci.
Leppa et al. 2016, Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families
, Am J Hum Genet.
Hinz and Geschwind 2017, Molecular Genetics of Neurodegenerative Dementias
, Cold Springs Harb Perspect Biol.