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NCI Team Probes Chromosomal Architecture

NCI Team Probes Chromosomal ArchitectureFigure 1TECH WATCH Though most cells in an organism contain the identical genome sequence, the same cannot be said for the genome's three-dimensional organization. Using high-resolution microscopy and a technique called chromosome painting, Tom Misteli, a cell biologist at the National Cancer Institute, and colleagues examined six chromosomes in eight mouse tissue types and found that chromosomes cluster differently in each tissue. While this could indicat

The Scientist Staff

NCI Team Probes Chromosomal Architecture

<p>Figure 1</p>

TECH WATCH Though most cells in an organism contain the identical genome sequence, the same cannot be said for the genome's three-dimensional organization. Using high-resolution microscopy and a technique called chromosome painting, Tom Misteli, a cell biologist at the National Cancer Institute, and colleagues examined six chromosomes in eight mouse tissue types and found that chromosomes cluster differently in each tissue. While this could indicate that the genome's spatial organization affects gene expression, "there is virtually no evidence for this," says Misteli.

Instead, genome organization correlates with chromosomal abnormalities. Every cancerous lymphocyte Misteli's team examined contained translocations among chromosomes 12, 14, and 15. In normal primary lymphocytes, these chromosomes physically cluster, indicating, says Misteli, that the "probability of two chromosomes undergoing translocation is directly related to their spatial proximity."

As not all cells in a tissue are exactly alike, the team examined several...

Human Antibodies from Mice

<p>Figure 2</p>

PATENT WATCH Mouse monoclonal antibodies, when introduced into humans, induce an immune response. So in the early 1990s, Raju Kucherlapati and colleagues at Cell Genesys (now Abgenix) created a way to use transgenic mice to make a completely human antibody. The work has garnered a number of patents, the most recent being US patent 6,673,986, issued on Jan. 6.

The method uses gene targeting of the J region of the immunoglobulin locus in mouse embryonic stem cells to inactivate both heavy and light antibody chains, says Kucherlapati, professor of genetics at Harvard University. Absence of the J region renders the genes inactive. The second step introduces the human immunoglobulin locus by using a yeast artificial chromosome that contains a substantial portion of the variable portion of the immunoglobulin gene. This is accomplished by spheroplast fusion, a method of introducing large segments of DNA into mouse embryos, Kucherlapati says. "By breeding these two different mice, we get a mouse in which endogenous genes are inactivated and human genes are activated," he explains.

Fremont, Calif.-based Abgenix http://www.abgenix.com has licensed the method to many other companies and academic collaborators, says and those interested licensing it should contact company.

- Ivan Oransky

Smart Pattern Finder

<p>Figure 3</p>

SOFTWARE WATCH In 1993, Gene Meyers, one of the founding fathers of bioinformatics, created ANREP, a program that searches for patterns in genetic sequences. Since then, ANREP has ruled the genomics world, though the program hasn't changed very much.

Now a new, open-source program threatens to challenge ANREP's dominance. Called SmartFinder http://bioinf.dimi.uniud.it/software/software/smartfinder, the tiny piece of software (its download is measured in kilobytes), uses a new algorithm to detect and identify complex motifs in DNA, RNA, or protein sequences. Its strength, says programmer Nicola Vitacolonna, a graduate student at the University of Udine, Italy, is its efficiency. "It can run multiple searches in a matter of minutes," he says. ANREP, in contrast, would take hours to run the same searches.

SmartFinder has few bells and whistles. It runs only in command-line format on Unix, Linux, and Mac operating systems, producing a data-rich FASTA file best viewed in genomics browsers such as Apollo http://www.ensembl.org/apollo. Vitacolonna is working on a graphical user interface, but it's not his top development priority, he says. Instead, Vitacolonna is optimizing the program to run different types of sequences, recognize different types of patterns, and employ weighted matrices.

So far the program has only a few users, says Vitacolonna, who plans to present the program officially in March. "I haven't done any advertising," he says, "but when people find out about it, they'll use it."

- Sam Jaffe

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