Richard Myers
Title
Professor
Department
Genetics
Research Interests
Genetic, biochemical and cellular basis of inherited human diseases, particularly those that affect the nervous system.
Phone
5-9687
Fax
725-9689
Address
SUMC, M-344
Mail Code: 5120
Faculty Research Description
We are interested in understanding the roles that genes play in a wide range of human phenotypes, including diseases, common traits and behaviors. We approach these studies with a variety of experimental strategies, including large-scale sequencing of the human and mouse genomes at the Stanford Human Genome Center, genome-wide and gene-specific identification of DNA variation in the human genome, the use of genomic and genetic information to identify human disease genes,
and the application of biochemical and animal model approaches to elucidate the functions of disease genes. Our Sequencing Group at the Stanford Human Genome Center, which is located just off the Stanford campus, is collaborating with the Joint Genome Institute in Walnut Creek, California, with funding from the Department of Energy, to produce highly accurate finished DNA sequences of large segments of the human genome, as well as homologous regions of the mouse genome. The human segments that we are focusing on comprise about 10% of the human genome, and include chromosomes 5, 16 and 19. While many of the sequencing projects pay special
attention to interesting biological regions, such as genes involved in diseases or large gene-family clusters, all the sequencing data generated by the Joint Genome Institute and our group are made available, in both unfinished and finished form, in GenBank and on our web pages, for unrestricted use by the scientific community as soon as they are generated. We pay particular attention to producing finished sequence of the highest practical accuracy - our finished sequence contains no gaps and has an estimated base pair error rate of fewer than one error in more than 500,000 base pairs. The sequences that we finish, including quality scores and downloadable files, can be
obtained from GenBank and from our web page (http://www-shgc.stanford.edu).
In mylaboratory in the Department of Genetics at the Stanford University School of Medicine, we collaborate with Dr. Neil Risch and the Stanford Autism Genetics Group to search for genes involved in autism, a neurodevelopmental disorder. In another collaboration, we work with Dr. Alice Whittemore and her colleagues to study genes involved in breast and ovarian cancer. My laboratory used similar approaches to show that mutations in the cystatin B gene are responsible for Progressive Myoclonus Epilepsy (EPM1), to identify the weaver gene, which is responsible for aberrant cerebellar development in the mouse, and, with Dr. Matthew Scott and colleagues, to
identify a gene involved in the most common form of skin cancer. We are also developing new biochemical methods for discovering single nucleotide polymorphisms in the human genome, genomic approaches for studying natural variation in expression levels of genes in different people, and molecular and computational approaches to identify regions of the human genome that regulate gene expression. Finally, my laboratory studies the functions of the genes responsible for Huntington disease (HD) and EPM1. We have used embryonic stem cell techniques to mimic in mouse the mutations that result in these diseases in humans. Our HD mouse model demonstrates behavioral abnormalities and electrophysiological aberrations suggestive of some features of the disease, and our EPM1 mouse model has symptoms of progressive ataxia, myoclonic epilepsy, corneal degeneration and cerebellar apoptosis, providing a heretofore undiscovered link between cystatin B and programmed cell death. We are using comparative genomics, biochemical and cell
biological methods to study further the normal and pathological functions of the HD and EPM1 proteins.
Pennacchio, L. A., Bouley, D. M., Higgins, K. M., Scott, M. P., Noebels, J. L., and Myers, R. M. (1998).
Progressive ataxia, myoclonic epilepsy, and cerebellar apoptosis in cystatin B-deficient mice. Nature
Genet. 20: 251-258.
Shelbourne, P.F., Killeen, N., Hevner, R.F., Johnston, H.M., Tecott, L., Lewandoski, M., Ennis, M.,
Ramirez, L., Li, A., Iannicola, C., Littman, D.R., and Myers, R.M. (1999). A Huntington's disease CAG
expansion at the muring Hdh locus is unstable and associated with behavioural abnormalities in
mice. Hum. Molec. Genet. 8: 763-774.
Usdin, M., Shelbourne, P. F., Myers, R. M. and Madison, D. V. (1999). Impaired synaptic plasticity in
mice carrying the Huntington's disease mutation. Hum. Molec. Genet. 8: 839-846.
Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., et al. and Myers, R. M. (1999). A
genomic screen for autism: Evidence for a multi-locus etiology. Am. J. Hum. Gen. 65: 493-507.
Li, Z., Karlovich, C. A., Fish, M., Scott, M. P. and Myers, R. M. (1999). A putative Drosophila homolog
of the Huntington disease gene. Hum. Molec. Genet. 8:1807-1815.
Areas of Study
SBRC