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Tracking the production of multiple proteins from one gene
  

 

The sequencing of the human genome revealed that humans have far fewer genes than proteins. This discovery raises an important question for biomedical researchers: How do the approximately 30,000 human genes produce 150,000 or more human proteins? The answer is through a process called alternative splicing, in which cells essentially cut and paste the same genetic material to create templates for different proteins. Scientists have developed a method for tracking the process in action.


Detail of the technology platform and experimental strategy. View full

Xiang-Dong Fu, of the University of California, San Diego, and colleagues used DNA microarrays and fiber optics to study the gene-to-protein production cycle. The method involves tracking short bits of genetic material that enable one gene to produce a variety of proteins through alternative splicing. The researchers were able to show unique genetic signatures that reveal which portion of a gene is active when producing the different proteins.

The researchers catalogued alternative splicing patterns of nearly 100 different genetic targets tested simultaneously on up to 16 arrays. The ability to profile targets on an increasingly larger scale may allow researchers to discover patterns of alternative splicing that are important during cancer or other biological processes.

Ideally, researchers would like to have tools to measure alternative splicing patterns as they occur in different tissues, during the process of development, or in the progression of human disease, according to Paula Grabowski, of the University of Pittsburgh, Pennsylvania, who wrote a commentary accompanying the study in Nature Biotechnology. So far, she observes, such tools have been lacking.

The new method represents "an important advance for the detection of such subtle differences," says Grabowski. "It should also serve as an important stepping-stone to the development of even more powerful methods for analyzing gene expression as a function of changes in physiology, development, and disease."

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Grabowski, P. Alternative splicing in parallel. Nat Biotechnol 20, 346-347 (April 20, 2002).
 
Yeakley, J.M. et al. Profiling alternative splicing on fiber-optic arrays. Nat Biotechnol 20, 353-358 (April 20, 2002).
 

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