Most genes undergo alternative splicing, producing two or more different proteins. Then, there are pseudogenes — genes that look functional but aren't. Some of these are "dead genes," according to University of California at Santa Cruz bioinformatician David Haussler. "They once had a function," he says, "but they have accumulated enough mutations to slowly decay and become worthless." Distinguishing functional genes from pseudogenes is not trivial.

Thanks in part to the mouse genome, completed last year (see Paper View, Feb. 2003 Bio·IT World), the emerging consensus is that the total number of human genes is less than the initial 30,000 estimate. But uncertainty remains, and Haussler concedes that "computational prediction of genes is simply very hard." New programs such as TwinScan from Washington University in St. Louis, and Genomix's EXP6, are assisting efforts to not only identify novel genes but also confirm the existence of "dark genes" — those predicted by computer programs but unverified by other techniques.

AnVil and Applied Biosystems (ABI) collaborated to shed light on the "dark" genome using PCR (polymerase chain reaction) methods with TaqMan, microarrays, and AnVil's advanced analytics, to study about 10,000 putative genes. AnVil designed the analytical program that "determines whether the lab data are hard evidence that these are genes," AnVil's John McCarthy says. Once "found again," those genes will help finalize the actual number of genes. ABI reports that 2,400 to 2,500 genes were confirmed after screening 9,500 predicted ones. Aside from the inherent scientific interest, "The assays for those genes will make a nice addition to our offering," ABI's Raymond Samaha says.

Ultimately, identifying all genes will be a walk in the park compared to what lies ahead. Eric Green of the National Human Genome Research Center says: "We will find all the genes. But we aren't even in diapers yet in terms of finding all the other stuff — the functionally important sequences and the regulatory elements."

—Malorye Branca

Back to Beyond the Blueprint