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Human Genome News Archive Edition

Human Genome News, January 1993; 4(5)

Whitehead-MIT Genome Center to Map Entire Genome

The NIH National Center for Human Genome Research (NCHGR) has awarded a grant totaling $8.3 million in the first year to the human genome center headed by Eric Lander at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology (MIT). The grant will renew and expand the work of Lander and his colleagues in (1) constructing physical maps of mouse and human genomes and (2) further refining mouse genetic linkage maps. These researchers developed and tested techniques for genome-wide mapping when they constructed a genetic linkage map covering the entire mouse genome.

"Progress in physical mapping has been greater than we expected in our planning for the Human Genome Project," says NCHGR Deputy Director Elke Jordan. "It is prudent for us at this time to take full advantage of newly developed mapping technologies to speed the project along so the tools can be delivered to the scientific community as quickly as possible."

Investigators have previously constructed physical maps one chromosome at a time, but improved and more-automated technologies, including mega-yeast artificial chromosome (YAC) clones, have led the Whitehead-MIT center group to attempt physical mapping of all mouse and human chromosomes at once.

Whitehead-MIT center activities will consist of three research projects and six core facilities. The research projects and their directors are the following:

  • Mouse genomic mapping [Lander and David Page (Whitehead-MIT)];
  • Human genomic mapping [Lander, Page, Nic Dracopoli (MIT), Daniel Cohen (Centre d'etude du Polymorphisme Humain {CEPH} and Genethon), and Jean Weissenbach (Institute Pasteur and Genethon)]; and
  • A pilot study to introduce YACs into the mouse germline [Rudolph Jaenisch (Whitehead-MIT)].

The core facilities include:

  • Informatics [Nathan Goodman (Whitehead Institute), James Orlin (MIT), and Joseph Nadeau (Jackson Laboratory)];
  • DNA sequencing;
  • Instrumentation [Lander, Paul Matsuidaira (Whitehead-MIT), and Cohen];
  • Materials [Cohen, Shirley Tilghman (Princeton University)]; and
  • Administration.

New Markers To Be Identified

Work on mouse and human genomes will allow scientists to compare information about gene structure and function in the two species. The mouse and human genomes are more than 90% homologous, and many mouse genes carry out functions identical to their human counterparts. Several disease-related genes identified in mice have been found to be similar in humans.

Lander and his coworkers will generate from the mouse genome 6000 markers of simple sequence length polymorphisms (SSLPs) spaced an average of 300,000 bp apart. This set of markers will allow scientists to locate individual genes quickly and separate the contributions that several genes may make to a single trait or disease.

The group will also identify 10,000 sequence tagged site (STS) markers covering the whole mouse genome at a low-resolution rate of about 1 STS every 300,000 bp of DNA. Further work will be needed to increase the resolution of the physical map to 1 STS every 100,000 bp as called for in the 5-year plan for the Human Genome Project. SSLPs, which can also serve as STSs, will be used to tie information from the genetic map to the physical map. Center researchers will develop a YAC library of cloned DNA from the mouse genome and order the clones using STSs.

Because the data generated will be critical to physical mapping efforts by the community of genome scientists, center researchers have developed a policy to ensure access to materials and information. (See margin text on sharing policy.) The CEPH mega-YACs, now at the Whitehead genome center, have been copied and distributed to three centers, which are now making additional copies for wide distribution to researchers.

Whitehead-MIT Genome Center Sharing Policy

All clone libraries, marker sequences, and maps will be distributed promptly and will not be patented. As soon as results are confirmed and before publication, data will be released in batches into the public domain. No access to materials or information will be granted to any commercial entity before public release.

In October 1992 Page and Cohen independently published the first physical maps of entire human chromosomes (Y and 21, respectively). [See Science 258, 52-86 (October 2, 1992); Nature 359, 380-86 (October 1, 1992); and HGN 4(4), 1-4 (November 1992).]

Anne Adamson
HGMIS, Oak Ridge National Laboratory

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Human Genome Project 1990–2003

The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.

Human Genome News

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