Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, January 1994; 5(5)
Investigators from Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, and University of Wisconsin (UW) have localized Mom1, a modifying gene that affects development of colon tumors in mice carrying the cancer-promoting gene Min1. Min1 causes multiple intestinal neoplasia (Min) syndrome, which is equivalent to familial adenomatous polyposis coli (FAP) in humans and thus presents a useful model for studying FAP and other colon cancers. Mom1 (for modifier of Min1) maps between the markers D4MIT12 and D4MIT13 on distal chromosome 4.
FAP is an inherited human disease associated with hundreds to thousands of colon polyps and a high incidence of colon cancer, a common malignancy in industrialized countries. As with many other human diseases, colon cancer is polygenic caused by the interaction of several genes that may modify each other's expression. The severity of FAP varies among individuals who inherit identical mutations in their FAP genes; one person may have only a few colon polyps while another may develop numerous polyps as well as tumors elsewhere in the body. Possible explanations for such variations are the presence of a modifying gene, environmental considerations such as diet, or a combination of factors.
Researchers used the Whitehead mouse genetic maps then consisting of more than 2000 different genetic markers to compare the inheritance patterns of disease severity (colon tumor number) with those of the markers. The dense genetic maps also offer a powerful new way to explore genetic origins of other diseases that exhibit much natural variation; these diseases include hypertension, diabetes, and atherosclerosis.
Mouse model systems offer a powerful research tool for studying complex interactions related to cancer development. Investigators in this study used mice carrying a small mutation in their homolog (gene counterpart) of the FAP-causing human gene; they found tumor reduction or even total suppression in mice that also carried the Mom1 modifier gene, thus proving that a modifier gene affects the expression of an inherited cancer. Modifier genes are far more difficult than other types of genes to locate in mammals.
The next steps will be to sequence the Mom1 gene and identify its human homolog, events which could have important diagnostic implications for human families. Understanding how modifying genes exert their effects on cancer-promoting genes may one day lead researchers to develop new forms of cancer therapy.
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Human Genome Program, U.S. Department of Energy, Human Genome News (v5n5).
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.
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