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Science 306 (5696): 690-695

Copyright © 2004 by the American Association for the Advancement of Science

In Silico Genetics: Identification of a Functional Element Regulating H2-E{alpha} Gene Expression

Guochun Liao,1* Jianmei Wang,1* Jingshu Guo,1 John Allard,1 Janet Cheng,1 Anh Ng,1 Steve Shafer,2 Anne Puech,3 John D. McPherson,4 Dorothee Foernzler,5 Gary Peltz,1{dagger} Jonathan Usuka1

Abstract: Computational tools can markedly accelerate the rate at which murine genetic models can be analyzed. We developed a computational method for mapping phenotypic traits that vary among inbred strains onto haplotypic blocks. This method correctly predicted the genetic basis for strain-specific differences in several biologically important traits. It was also used to identify an allele-specific functional genomic element regulating H2-E{alpha} gene expression. This functional element, which contained the binding sites for YY1 and a second transcription factor that is probably serum response factor, is located within the first intron of the H2-E{alpha} gene. This computational method will greatly improve our ability to identify the genetic basis for a variety of phenotypic traits, ranging from qualitative trait information to quantitative gene expression data, which vary among inbred mouse strains.

1 Department of Genetics and Genomics, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304–1397, USA.
2 Department of Anesthesia, Stanford University Medical Center, Stanford, CA 94305, USA.
3 Centre National de Génotypage, 2 rue Gaston Crémieux, CP 5721, 91057 Evry Cedex, France.
4 Department of Genetics and Genome Sequencing Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
5 Roche Center for Medical Genomics F. Hoffmann–La Roche, RCMG, Bau 93/4.26, CH-4070 Basel, Switzerland.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: gary.peltz{at}roche.com


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