Mouse Map Leads Way To Human Disease Exploration

May 18, 1999

LOS ANGELES (May 18, 1999) - Scientists studying virtually any human genetic disease or trait can now quickly locate known matching genes in the mouse by using a color-coded chromosome mapping system devised by a team led by Julie R. Korenberg, M.D., Ph.D., Cedars-Sinai Vice Chair for Research in the Department of Pediatrics.

The dramatic finding, featured on the cover of the May 1999 issue of the scientific journal Genome Research, has profound implications for the study of human illnesses and the hunt for effective treatments and cures. As an example, Dr. Korenberg's own research into Down Syndrome will be greatly speeded by her ability to study the effects of potential therapies in mice proven to have an analogous chromosomal abnormality to one seen in humans.

In the past, creating and identifying a mouse with three copies of Chromosome 16 -- a mistake that produces traits comparable to those seen in human Down Syndrome -- could take months and countless trial-and-error attempts.

"Now it's so clear," she said, describing three bright spots in every nucleus of a mouse's cells. Indeed, the error can even be seen in embryonic mouse cells, holding the promise of developing cures that could one day be carried out in fetuses with Down Syndrome so that babies would be born without the disease.

"We are quite excited," said Dr. Korenberg. "These are keys to the secrets of how humans see, hear, think, and how they become ill." Recent years have seen an "enormous national effort to understand what humans have in common with mice," she explained.

In today's renaissance of human genetics, as more and more genetic explanations have been found for human disease and behavior, the potential of applying that knowledge to a workable animal model -- the mouse -- has never been more critical.

But the mouse, with its 40 chromosomes and 3,000 megabases of genes, has eluded easy study.

Unlike human chromosomes, which are more easily recognized and increasingly well mapped by the Human Genome Project, looking for a mouse chromosome can be like searching for a blade a grass in a football field.

The mapping system devised by Dr. Korenberg and her associates over five years, affixes a color to each tiny segment of every chromosome in the mouse genome. Red might identify Chromosome 1, with a purple hue marking the middle section and pink for the distal end. By the order or presence of a color or colors, a scientist will know the genetic makeup of a mouse from one drop of its blood.

A mouse with a gene analogous to the human gene for familial hypertension might have a distinctive pattern of blue, purple, bright orange, then green within a certain region of its DNA. In the past, scientists would breed mice with such traits and hope that perhaps one within a litter of six would be the perfect model. But detecting which mouse, if any, carried the desired gene was a virtual fishing expedition.

"We're narrowing the search from 3000-million base pairs to 10-million base pairs-or less than 1% of the gene. It really starts to pinpoint that needle in a haystack," said Dr. Korenberg.

The study also tracks the beginnings and endings of strings of mouse chromosomes, so that scientists hunting for a particular "address" within the genome will have a better neighborhood map within which they can focus their search.

"We have located mouse markers that can be used to help find every disease," she said.

The paper's title in Genome Research, Vol 9, #5, 1999, is, "Mouse Molecular Cytogenetic Resource: 157 BAC's Link the Chromosomal and Genetic Maps."

Dr. Korenberg, the primary investigator, holds the Brawerman Chair of Molecular Genetics in the Medical Genetics Birth Defects Center at Cedars-Sinai Medical Center and is Professor of Pediatrics and Human Genetics at the University of California, Los Angeles. Her associates on the study were Xiao-Ning Chen, M.D., of Cedars-Sinai; Bruce W. Birren, Ph.D., assistant director of the Sequencing Center at the Whitehead Institute of the Massachusetts Institute of Technology's Center for Genome Research; and Mary L. Oster-Granite, Ph.D., of the Department of Biomedical Sciences at the University of California at Riverside.
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Cedars-Sinai Medical Center

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