Uncovering New Links to Lung Cancer in Mice
For years, scientists have been hunting for genes involved in different types of lung cancer, such as pulmonary adenocarcinoma and squamous cell carcinoma. However, smoking and other environmental factors can obscure the genetic basis of human lung cancers, making animal models important for researchers in the field. In the July issue of Genome Research, Giacomo Manenti, Tommaso Dragani (both at the Istituto Nazionale Tumori, Milan), and colleagues report mapping a pulmonary adenoma susceptibility locus (Pas1) to a restricted region of mouse chromosome 6, laying the basis for cloning the mouse Pas1 gene and providing essential clues for identifying similar genes in humans.
The researchers employed a method for locating disease genes called linkage disequilibrium (LD), an approach previously applied chiefly to human populations. In LD, scientists scan for unique DNA markers that occur more frequently in affected individuals than in normal individuals. Markers displaying strong linkage with a disease may indicate the location of responsible genes. By comparing markers from strains of mice susceptible to lung tumors to markers from tumor resistant strains, Manenti and colleagues pinpointed a group of markers linked to pulmonary adenomas and placed the Pas1 locus to within 1.5 megabases on mouse chromosome 6. They also found that the different susceptible strains likely inherited their Pas1 mutations from the same ancestral source, a discovery that will facilitate cloning the Pas1 lung cancer gene in mice.
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Contact Information:
Tommaso A. Dragani
Department of Experimental Oncology
Istituto Nazionale Tumori
Milan
Italy
Email: dragan@istitutotumori.mi.it
Fax: 39-02-2390642
Color Me Three Ways: The Evolution of Trichromatic Vision
When next you see a rainbow, give silent thanks to gene duplication. The ability of humans and Old World primates to distinguish between short-, middle-, and long-wave visible light is based on our possession of 3 different genes for the visual pigment protein opsin. Previous research indicates that we acquired separate middle-wave (MW) and long-wave (LW) opsin genes by duplicating an ancestral MW/LW gene into a tandem gene array some 40 million years ago, an event that conferred trichromatic vision on all Old World primates. In the July issue of Genome Research, Kanwaljit Dulai, David Hunt (both at the University College London), and colleagues shed more light on the evolutionary history of primate trichromatic vision by comparing the DNA sequences of opsin genes from Old World and New World primates. Their work also provides clues to mechanisms underlying color vision anomalies in humans.
In contrast to Old World primates, New World primates (such as marmosets) generally possess only two opsin genes, one for short-wave opsin and one corresponding to the ancestral MW/LW gene in Old World primates. Dulai and colleagues performed comparisons of upstream sequences, i.e., the sequences preceding the genes themselves, which are important for turning the genes on or off. The researchers demonstrate that the sequence upstream of the marmoset MW/LW gene strongly resembles the sequence upstream of the LW gene in humans and Old World primates. This upstream sequence homology extended all the way into a special gene control region previously identified only in Old World primates. On the other hand, comparison of the marmoset MW/LW gene upstream sequence with the Old World MW gene upstream sequence revealed that homology between these sequences ends abruptly 236 base pairs away from the start of the MW gene. These results strongly suggest that this homology end point is the site of the ancestral gene duplication and insertion. The researchers also identify the remnants of "jumping gene" sequences, called Alu elements, at several locations upstream of the human MW gene, providing a possible mechanism for the duplication event. These Alu elements may also explain the ease of opsin gene loss and duplication that sometimes leads to colorblindness and other visual anomalies in humans.
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Contact Information:
David M. Hunt
Department of Molecular Genetics
Institute of Opthamology
University College London
London EC1V 9EL
United Kingdom
Email: d.hunt@ucl.ac.uk
Fax: 44-171-608-6863
Closing in on Male Germ Cell Tumors
Tumors often develop due to mutations in so-called tumor suppressor genes (TSGs) that normally regulate cell division. For example, recent work suggests that deletions of unidentified TSGs on chromosome 12 cause most male germ cell tumors, which commonly affect young men from 20-35 years of age. In the July issue of Genome Research, Vundavalli Murty (Columbia University), Raju Chaganti (Memorial Sloan-Kettering Cancer Center), and colleagues report constructing a detailed map of the chromosomal region responsible for male germ cell tumors. Using DNA markers generated from the map, the researchers also narrowed the location of the candidate TSGs by identifying the markers that were deleted in germ cell tumor DNAs. The construction of a detailed physical map and the refinement of the tumor suppressor gene locus prepares the stage for the complete sequencing of this region and the likely identification of new tumor suppressor genes involved in male germ cell tumors.
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Contact Information:
Vundavalli Murty
Department of Pathology
College of Physicians & Surgeons of Columbia University
New York, NY 10032
Email: vvm2@columbia.edu
Fax: 212-305-5498
For complete manuscript or additional information, please contact:
Peggy Calicchia
Editorial Assistant
Genome Research
1 Bungtown Road
Cold Spring Harbor, NY 11724
phone: 516-367-6834
fax: 516-367-8334
email: calicchi@cshl.org
Ask for the following titles:
Closing in on Male Germ Cell Tumors
Uncovering New Links to Lung Cancer in Mice
Color Me Three Ways: The Evolution of Trichomatic Vision
Journal
Genome Research