Assessing the function of unknown genes is feasible and can be done with a microarray phenotype

Microarrays provide a method of quantifying the expression and order of genes in a particular genome -- acting as a surrogate measure of cell physiology, said researchers at Baylor College of Medicine in a report that appears online today in the journal Nature Genetics.

"Microarray data are good phenotypes to determine the order of genes and are a good surrogate measure of cell status," said Dr. Gad Shaulsky, associate professor of molecular and human genetics at BCM.

Microarrays are fairly new technology that can help scientists understand how genes interact as well as how they are regulated by networks within the cell. They are created by the placement of tiny droplets of functional DNA on glass slides. Then researchers attach fluorescent labels to nucleic acids (DNA or RNA) from the cells under study. These labeled nucleic acids are allowed to bind to the DNA on the slides. Researchers then use a microscope to measure how much of a specific nucleic acid is present.

Genotype is the genetic fingerprint of a particular cell. Phenotype is the outward manifestation of the genotype. For example, a person may have genes for eye color. That is that individual's genotype. Blue eyes is the phenotype.

The microarray data Shaulsky and his collaborators used show that they can determine the order in which genes act in a cascade that results in a particular phenotype.

Shaulsky and his co-authors performed their work in Dictyostelium (Dictyostelium discoideum), a form of soil amoeba used in the laboratory because many of its 10,000 genes are homologues or equivalents of genes found in humans.

Using microarray data alone, they determined the orders in which genes function in a particular pathway in that organism. The protein kinase A (PKA) signaling pathway occurs when the organism encounters starvation. The pathway enables the single cells to combine into a multi-cell organism.

"We pretended we did not know the order of genes in the pathway," said Shaulsky. "We were able to reconstruct the pathway from the microarray data. This means the microarray provides a good phenotype that is quantitative. We can prove that gene A comes before gene B and give mathematical support for these findings."

"This is a proof of principle that we set out to do – assessing the function of unknown genes is feasible," said Shaulsky. "It can be done with a microarray phenotype."

Others who participated in the research included Drs. Nancy Van Driessche, Ezgi O. Booth, Paul Hill and Adam Kuspa, all of Baylor College of Medicine; and Janez Demsar, Peter Juvan and Blaz Zupan of the Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.