Human Genome Project Completes Genetic Map of Mouse DNA

Human Genome Project Completes Genetic Map of Mouse DNA

March 13, 1996

BETHESDA, Md. - Human Genome Project (HGP) researchers have completed a dense "genetic map" of the DNA of the laboratory mouse (1). The lab mouse is one of the best-studied animals in genetics, and its genetic information is about 75 percent similar to that of the human. The publication of the mouse linkage map in the March 14 issue of the journal Nature, along with a separate linkage map of the human genome (2), marks the completion of the HGP's large-scale genetic mapping efforts.

"Dense genetic maps make possible the identification of genes for single-gene disorders and the dissection of [multi-gene] traits," said officials of the National Human Genome Research Institute (NHGRI) in an accompanying editorial (3). According to NHGRI Director Francis Collins, and Deputy Director Elke Jordan, "... these two groups have already changed the face of human and mouse biology."

NHGRI is the component of the National Institutes of Health (NIH) that oversees the NIH role in the HGP, a 15-year research effort to characterize the details of human DNA and the DNA of a few important laboratory animals.

The HGP effort to map the mouse genome began five years ago. The final map, was constructed by Eric Lander at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology, and their colleagues. This map contains 7,377 markers scattered along the chromosomes - 1 every 400,000 nucleotide bases on average. Although the mouse genome is about the same size as that of the human, it is packaged in 20 chromosome pairs instead of 23. The new map provides dense marker coverage of all 20 mouse chromosomes. A full spelling out of all the markers would require over 500 journal pages, the report says, so the complete marker information is being made available on the Internet at the Whitehead Institute [wi.mit.edu].

A major advantage of the new mouse map is its usefulness in mapping the genetic origins of diseases or traits. Even before researchers have identified the gene actually responsible for a trait, mapped markers tell them roughly how close by the gene is. The more markers there are on the map, the more likely one will be closely linked to a disease gene, and the easier it will be to zero in on that gene. The mouse is particularly useful in the study of inherited traits. For nearly 100 years, scientists have been developing strains exhibiting specific variations in genetic make-up. Even though these traits are often easy to see, little is known about the underlying genetics that cause them.

In health research, investigators often study mouse diseases that mimic human diseases to learn their causes and treatments, and then apply what they've learned from the mouse to similar diseases in humans. A paper in the same issue, by Jean Weissenbach at the French company Genethon, and his colleagues, also provides a powerful tool for these comparisons. That group has constructed a genetic map of the human genome that, like the mouse map, consists of high-quality, DNA-sequence based markers known as microsatellites, which are easy to use in the laboratory.

These maps have already helped researchers pinpoint and isolate genes for many diseases caused by alterations in a single gene. "Mapping disease [characteristics] by linkage analysis used to be a daunting task, one outside of the reach of many relatively sophisticated ... laboratories," said Collins and Jordan. "The new maps have changed all that - mapping a single-gene disorder ... can now be accomplished in a modest-sized lab in a few months."

The new maps also give researchers better tools for teasing apart the genetics of disorders, such as diabetes, asthma, cancer and high blood pressure, that result from subtle alterations in more than one gene. Laboratory animals are particularly helpful in these studies because the studies often require analyzing genetic information from thousands of related individuals over several generations.

With the genetic maps for both human and mouse now complete, Collins and Jordan say the second phase of the HGP will entail completing so-called "physical maps" of the human genome - organized sets of isolated and mapped DNA pieces representing all the DNA in the genome. For the human, this will likely be completed in the next two years.

The NHGRI, one of the components of NIH, is a major partner in the HGP, the international research effort to map the estimated 100,000 genes and read the complete set of genetic instructions encoded in human DNA. NHGRI also supports research on the application of genome technologies to the study of inherited disease, as well as the ethical, legal and social implications of this research. For more information about NHGRI or the HGP, visit our World Wide Web site at www.genome.gov.

Footnotes

1. A comprehensive genetic map of the mouse genome. William F. Dietrich, et al., Nature, vol. 380, pp.149-152, March 14, 1996.
2. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Colette Dib, et al. Nature, vol. 380, pp.152-154, March 14, 1996.
3. A march of maps. Elke Jordan and Francis Collins, Nature, vol 380. pp. 111-112. March, 14, 1996.

Contact:
Leslie Fink or Sharon Durham
National Human Genome Research Institute (NHGRI)

Eve Nichols or Seema Kumar
Whitehead Institute
Phone: (617) 258-5183