Research
Emphasis Areas

Major Research Domains

Research Affiliates

Core Services
  Behavioral
  Science Core

  Genetics Core

  Infant Primate
  Research
  Laboratory

  Instrument
  Development
  Laboratory

  Neuroscience Core

Research Emphasis Area on Fragile X Syndrome

Coordinator: Charles Laird, Ph.D.

Fragile X syndrome is an inherited disorder with symptoms of mild to severe intellectual disability. A wide range of altered cell and molecular phenotypes is caused by an expansion of a triplet repeat within, and epigenetic inactivation of, a single gene, FMR1. New and deeper analyses of molecular and clinical data have revealed a greater diversity of clinical and molecular phenotypes in Fragile X families than was previously evident. For example, members of the Seattle-Davis Fragile X Research Center have described and characterized a related syndrome, Fragile-X-Associated Tremor Ataxia (FXTAS), a neurodegenerative disorder. 

A central goal of the Fragile X REA is to understand the molecular organization at the FMR1 locus through research on chromatin structure; epigenetic signaling through DNA methylation, including stem cells; transcriptional control, especially as influenced by CTCF protein; sense and antisense transcripts from the Fragile X region and their functions; control of RNA processing to give the various FMR-protein isoforms; and origins and timing of DNA replication.  Investigators in our REA group, in cooperation with the Neurodegenerative Disorders REA, are also examining the neurogenetic effects of over-expression of this locus in a mouse model of FXTAS. Additional work investigating possible common neural correlates of Fragile X syndrome and autism is also being pursued. 

Our REA is also the catalyst for collaboration with leaders in clinical and basic research of Fragile X and FXTAS at other institutions. The Fragile X Research Center based at the CHDD is a cooperative effort between the University of Washington and the University of California at Davis, and serves as the organizing framework for these collaborations.  The broader goals of this center program are to integrate themes of molecular-clinical phenotype correlations, the basis of cell-cell mosaicism, molecular genetics and epigenetics of the Fragile X locus, and families with Fragile X.  Related research of this consortium under the Fragile X Research Center will now include newborn screening with follow-up family counseling, characterization of the various protein isoforms of FMR-protein, exploration of the contributions of these various isoforms to the neurophysiology, and neuro-cell biology of Fragile X.  Additional work is designed to assess the population-based incidence of newborns with Fragile X pre- and full-mutation alleles, and to assess the efficacy of early counseling and intervention in families with newborns with such alleles.

Faculty Investigators

• Charles Laird, Ph.D., Professor, Biology, Coordinator
• Thomas Bird, M.D., Professor, Medicine, Neurology, and Medical Genetics
• Christene Disteche, Ph.D., Pathology
• Gallina Filippova, Ph.D., Staff Scientist, Human Biology, Fred Hutchinson Cancer Research Center
• Stanley Gartler, Ph.D., Professor Emeritus, Medicine and Genetics
• Gwen Glew, M.D., Assistant Professor, Biochemistry
• R Scott Hansen, Ph.D., Research Associate Professor, Medical Genetics
• David Morris, Ph.D., Professor, Biochemistry
• Stephen Tapscott, M.D., Ph.D., Professor, Neurology
• Sara Webb, Ph.D., Research Assistant Professor, Psychiatry and Behavioral Sciences. 

Faculty Investigators from Collaborating Institutions

• Elizabeth Berry-Kravis, M.D., Ph.D.
• William Greenough, Ph.D.
• Paul Hagerman, M.D., Ph.D.
• Randi Hagerman, M.D.
• Flora Tassone, Ph.D.