[CSBi-events] Seminar: From Mouse Genetics to Human Therapeutics

[csbi-events@mit.edu]

 From Mouse Genetics to Human Therapeutics

Time: Wednesday (11/10/04) at 4:00 PM
Location: 68-181

Gary Peltz, M.D., Ph.D

Department of Genetics and Genomics
ROCHE, Palo Alto, CA


Our understanding of genetic factors effecting human disease
susceptibility and the response to drug treatment is advanced by
analysis of murine genetic models.  As one example, a murine genetic
model of osteoporosis was analyzed, and a novel pathway regulating bone
development was identified.  However, a significant amount of time and
cost is associated with the conventional methods used for mouse genetic
analysis.  A novel computational method was developed to reduce the time
and cost required for mouse genetic analysis.  This method identifies a
causative genetic factor by correlating a pattern of observable
physiological or pathological differences among selected strains of mice
with the pattern of genetic variation. A haplotypic map of the genome,
based upon 150,000 SNPs identified from analysis of 1,900 genes across
20 commonly used laboratory mouse strains (http://mouseSNP.roche.com),
was produced.  This map was used to develop a method for rapid,
haplotype-based, computational identification of the genetic basis for
observed physiologic and pathologic differences among inbred strains.
This computational method correctly predicted the genetic basis for
strain-specific differences in multiple biologically important
phenotypic traits, and was used to identify a novel allele-specific
enhancer element regulating H2-Ea expression.  This method is now being
used to analyze the mechanism of action and metabolism of a commonly
prescribed medication.

References

In silico genetics: identification of a functional element
regulating H2-Ealpha gene expression. Science  306:690, 2004

Regulation of bone mass in mice by the lipoxygenase gene Alox15. Science
303:229, 2004

Contact:
Peter Sandy, Ph.D.
Center for Cancer Research
Tel: 617-324-8700
Email: psandy at mit.edu

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Dawn Davis Loring
Communications Coordinator
Computational and Systems Biology (CSBi)
Phone: (617) 324-0150
Fax: (617) 324-0081

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