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Effects of Multiple Copies of Genes on Disease Risk

dent Patrick Cahan and postdoctoral fellow Deepa Edwin, Ph.D. The 20 mouse strains were previously selected by the Mouse Phenome Project, which is assembling a database of how changes in mouse DNA affect mouse characteristics. The project is headquartered at Jackson Laboratory in Bar Harbor, Maine.

For their analysis, researchers compared the genome of each of the 20 mouse strains against that of the prototypical research mouse strain, C57BL/6J.

"That's the 'plain vanilla' mouse genome," Graubert explains. "Just like the reference human genome sequence that is used to identify genetic differences between human individuals, the C57BL/6J mouse genome is the one we understand best and the standard against which other mouse genomes can be compared."

Nimblegen's technique for rapid analysis is known as oligonucleotide array comparative genomic hybridization.

"The copy number variants we describe in this paper are numerous and fairly large—they vary in length between two thousand and two million DNA base pairs," Graubert says. "Datasets this large require a lot of analysis to be sure that what you're seeing is real, so we really worked hard to prove that these gene copy number variations are real and validated many of them using other technologies."

Graubert is working with Nimblegen to conduct a follow-up analysis of gene copy number variation in the mouse strains using an even more sensitive version of the technique. They are also testing how changes in gene copy number are reflected in RNA, the order slips for assembly of a gene's protein that are copied from DNA.

"The prediction is that if you have a higher gene copy number count, you'll see more RNA from that gene," he says. "But we need to test that on a genome-wide scale."

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