Genome Mapping

(The Scientist, Vol:10, #6, p. 14, March 18, 1996) W.F. Dietrich, J.C. Miller, R.G. Steen, M. Merchant, D. Damron, R. Nahf, A. Gross, D.C. Joyce, M. Wessel, R.D. Dredge, A. Marquis, L.D. Stein, N. Goodman, D.C. Page, E. Lander, "A genetic map of the mouse with 4,006 simple sequence length polymorphisms," Nature Genetics, 7:220-45, 1994. (Cited in more than 130 publications as of February 1996) MAP-MAKER: MIT biologist Eric Lander and his coworkers developed a comprehensive map of the mouse genome. Comments by Eric Lander, Massachusetts Institute of Technology, and William Dietrich, Howard Hughes Medical Institute, Harvard Medical School The paper reports a comprehensive genetic map of the mouse genome and, specifically, how genetic markers are arranged along the mouse genome. "Genetic maps are essential tools for doing any kind of genetic work," says Eric Lander, a professor of biology at the Massachusetts Institute of Technology and director of the Whitehead/MIT Center for Genome Research. A genetic map is essentially a diagram that describes how known marker sequences in the chromosomes separate and recombine between generations. "Such maps allow geneticists to follow the inheritance patterns of any mouse genome in detail," explains Lander. "[Researchers at] mouse laboratories can take interesting gene mutations and complex traits and pin them down to gene regions. Scientists can map genes that cause simple Mendelian traits and, at the same time, also track multi-gene causes of complex diseases, such as cancer and hypertension." Lander explains that researchers may use such genome maps to create models of mice that have, for example, a predisposition to cancer. "You could set up a cross between them and those that are normal and study the second- generation progeny, ask which are susceptible to cancer and which aren't, and correlate them to regions of the genome they inherited and which they didn't," he points out. "Looking at the sibship in a family of mice and looking in the region of the genome and the risk factors for cancer in these strains, the regions of the genome where multiple genes lie are in essence risk factors for cancer." William Dietrich, a Howard Hughes Medical Institute investigator and an assistant professor of genetics at Harvard Medical School, thinks the paper has been cited so often because, "regarding a large genome, [having] more markers does make a difference in research you can do. It allows scientists who work in mouse genetics to do experiments they couldn't do before and do genetic mapping on a finer scale." "What's distinctive about this map is that all of the genetic markers are DNA-based," Lander says. Previously, maps were based on visible traits that were caused by gene mutations. Various genes causing certain traits could be mapped relative to each other by arranging crosses between mutations. But crossing strains was limited to mixing only one mutation-and trait-at a time. "By virtue of DNA markers, the maps are applicable to many crosses," Lander states. Notes Dietrich: "By being highly variable between one mouse strain and another, it's possible to set up crosses of strains and have lots of differences-you watch the segregation of genomes." Lander comments that the Whitehead Institute has made the map relatively easy to use. Genetic markers have been available in the public domain on the Whitehead Web site (http://www.genome.wi.mit.edu) for about six months. The paper appeared in a special issue of Nature Genetics that carried the Whitehead map and a map of the human genome (G. Gyapay et al., 7:246-339, 1994). The five-year project began with a 300-marker map published in Genetics in 1992 (W. Dietrich et al., 131:423-47, 1992). Final project reports, Dietrich notes, will appear in an upcoming issue of Nature. According to Lander, his team's next step is to build a physical map of the mouse genome, which will show the order along a chromosome of recognizable sequence sites.

Genome Mapping

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