There May be Twice as Many Genes in the Human Genome than previously thought, Yale Researchers Find

A study by Yale University researchers provides preliminary evidence that there may be more than twice as many genes in the human genome than previously predicted.

Using an advanced genomic technique, researchers looked for all the genes on human chromosome 22. This is the next and necessary step in analyzing and understanding the human genome.

“These are very promising findings,” said first author John Rinn, a fourth-year graduate student in a molecular, cellular and developmental biology (MC&DB) at Yale. “We found that many of the known, related and predicted genes were verified to be expressed in the cell. More importantly, our study reveals twice as many transcribed bases than have been reported previously, potentially indicating that there are twice as many genes in the human genome.”

Rinn and his collaborators mapped all the coding regions-spots where genes are potentially located-of chromosome 22 using an advanced microarray technology. They found that a DNA microarray representing nearly all of the unique sequences of human chromosome 22 was constructed and used to measure global transcriptional activity in a complex tissue similar to the placenta.

Chromosome 22 is the most well studied human chromosome. Most of these known genes were verified in the study and an equal number of previously undiscovered sequences were also expressed. Rinn said the study, which was published in a recent issue of the journal, Genes and Development, is part of ongoing research in this area.

“Interestingly, a significant fraction of these novel fragments can be found in the mouse genome, further indicating their biological relevance,” said Rinn. “This study was a proof of the principle that we can find all the regions of a chromosome that are biologically relevant. In the future we will scale this process to tackle the entire human genome.”

Rinn’s study collaborators at Yale included principal investigator Michael Snyder, professor and chair of MC&DB; Mark Gerstein, associate professor molecular biophysics and biochemistry (MB&B) and computer science; Perry Miller, professor of anesthesiology and director of medical informatics; Ghia Euskirchen, postdoctoral fellow in MC&DB; Paul Bertone, graduate student in MC&DB; R. Martone, graduate student, Nicholas Luscombe, postdoctoral fellow in MB&B; S. Hartman, graduate student, Paul M. Harrison, postdoctoral associate in MB&B; F. Kenneth Nelson, research scientist and lecturer in MC&DB; and Sherman Weissman, M.D., professor of anesthesiology.