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Genome Project Approved for Renewal, Expansion

The National Center for Human Genome Research (NCHGR) of the National Institutes of Health has approved a renewal and expansion in scope of the Center for Genome Research at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology (MIT).

The new Whitehead/MIT Center will consist of a consortium involving scientists from five institutions: the Whitehead Institute, MIT, Princeton University, the Jackson Laboratory in Bar Harbor, Maine, and the Centre d'Etude de Polymorphisme Humaine (CEPH) in Paris, France. Local participants include Drs. Eric Lander, David Page, Rudolf Jaenisch, and Paul Matsudaira of the Whitehead Institute and the MIT Biology Department; Dr. Nathan Goodman of the Whitehead Institute; Drs. Nic Dracopoli and David Housman of the MIT Biology Department; and Dr. James Orlin of the Sloan School of Management.

The Center's primary objective will be to construct basic maps of the mouse and human genomes.

The maps will help scientists search for genes associated with human disease. Greater understanding of the genetic errors that cause disease should pave the way for new strategies in diagnosis, therapy, and disease prevention.

The dual emphasis on the mouse and human genomes reflects the importance of developing a framework for experimental research in genetics, Dr. Lander says. Most problems in human genetics come to an impasse when they reach the experimental phase. Scientists cannot perform controlled mating experiments in human beings or alter a specific gene to define its function in the whole organism.

One solution to this problem is to develop genetic models in experimental animals. The mouse offers many advantages for this work because scientists have identified thousands of mutants with specific genetic defects and developed scores of inbred strains with abnormal physiologic characteristics. In most cases, however, the genes involved are known only by their effects on body structure or function. Efforts to apply knowledge from the mouse system to the study of human disease depend on the ability to isolate and clone the actual genes based on their location in the genome.

The Research Program

The Genome Center's activities will consist of three research projects and six core facilities. Drs. Lander and Page are the principal investigators for the first research project, Mouse Genomic Mapping. They will work toward a high resolution genetic map and a low resolution physical map of the mouse. This map should speed efforts to find genes responsible for single-gene defects, to clone genes associated with polygenic diseases (disorders that reflect the combined influence of multiple genetic factors and the environment), and to trace the progression of genetic changes during tumor formation.

The second project, Human Genomic Mapping, will aim to construct a low resolution physical map of the human genome. It will be directed by Drs. Lander, Page, and Dracopoli of the Whitehead/MIT, and Dr. Cohen of CEPH.

Dr. Jaenisch, whose laboratory recently achieved the first germline transmission of yeast artificial chromosomes, YACs, will direct the third project, Introduction of YACs into the Mouse Germline.

Among the six core facilities are an Informatics Core and an Instrumentation Core. The Informatics Core will oversee the Center's many computer needs. It will involve Dr. Goodman, a noted expert on database design, Dr. Orlin, an expert on computer algorithms, and Dr. Joseph Nadeau of the Jackson Laboratory, an expert in mouse genetics who maintains a major computer database for the mouse genetics community.

The Instrumentation Core will be responsible for identifying targets for automation, and designing and implementing new instrumentation systems (contracting with outside engineering firms or labs to build devices). This Core will be directed by Drs. Lander, Matsudaira, and Cohen.

The Center's Administrative Core will be located at the Whitehead Institute; much of the mapping effort will be housed in rented space at 1 Kendall Square.

A version of this article appeared in the December 9, 1992 issue of MIT Tech Talk (Volume 37, Number 16).

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