Moyra Smith

Professor of Genetics, Pediatrics/Newborn, Anatomy & Neurobiology
School of Medicine

Ph.D., University College, London, 1972

M.D., Pretoria, South Africa, 1969

Phone: (949) 824-7312
Fax: (949) 824-2089

University of California, Irvine
C234 Med Sci I
Mail Code: 4475
Irvine, CA 92697

Human gene mapping
Research Interests:

Human gene mapping
Analysis of genes which play a role in mental retardation and behavioral problems
Analysis of allelic variation in human genes: genotype phenotype correlation
Analysis of genetic changes in human tumors

My research activities are interdigitated with my clinical responsibilities in Human Genetics and Inborn Errors of metabolism. Frequently clinical activities and research activities have proven to be synergistic. Diagnostic studies in a number of our patients with birth defects led to the identification of chromosome rearrangements or deletions. We were able to use cell lines from these patients in fine mapping of human genes to specific chromosomal regions.

Tuberous sclerosis is a dominantly inherited disease, which may lead to seizures, mental retardation and the development of tumors (hamartomas) in brain, kidney. Approximately 10 years ago we began clinical and genetic studies in TSC at UCI and we collaborated on linkage analysis in this disorder with national and international groups. Our studies led to the identification of genetic heterogeneity in TSC and to the assignment of the TSC2 gene to chromosome 16p13.3. Our studies at UCI revealed that hamartomas from TSC patients frequently show loss of heterozygosity fo markers on chromosome 16p13.3, indicating that deletions occur in this chromosomal region in some TSC hamartomas. This finding led us to hypothesize that the TSC2 gene acts as a tumor suppressor gene. The TSC2 gene was cloned by an International Consortium in 1996, and it was shown to have homology with the GTPase activating protein of the Rap oncogene. TSC1 gene was cloned by an International consortium in 1998. We are currently carrying out mutation analysis and genotype phenotype correlation in our patients with TSC.

As co–director of the Molecular Core of the UCI Mental retardation Research center I participate with other investigators in initiation and feasibility studies of projects involving analysis of genetic variation in genes which may play a role in Mental Retardation.

As co–investigator on the Autism Program Project at UCI I participate in studies aimed at identifying etiologically distinct sub–types of Autism and to map the loci relevant for each sub–type. There is a growing body of evidence that a gene or genes on chromosome 15 play a role in Autism. We have detected deletion of a marker in the chromosome 15q22 region in a child with Autism and are conducting studies to define which critical genes may be deleted in this child.
Publications Lamber, T. C., R. A. Schultz, M. Smith, C. Wagner-McPherson, L.D. McDaniel, T. Donlon, E. J. Stanbridge, and E. C. Friedberg. 1991. Functional complementation of ataxia-telangiectasia group D (AT-D) cells by microcell-mediated chromosome transfer and mapping of the AT-D locus to the region 11q22-23. Proc. Natl. Acad. Sci.USA 88:5907.
  Gomez, M. R. and M. Smith. 1992. The Tuberous Sclerosis Complex, In Conneally (ed.) Molecular Basis of Neurology. In press.
Graduate Programs Cancer Biology

Research Center Autism Program Project
Link to this profile
Last updated 04/08/2002