CLEVELAND -- When the landmark publication of the human genome sequence appeared February 12 in the journals Science and Nature, three of the authors came from Case Western Reserve University's School of Medicine -- Joseph Nadeau, Evan Eichler, and Jeffrey Bailey. The three are with the Department of Genetics, a joint department with University Hospitals of Cleveland.
The papers revealed that humans have 30,000 to 40,000 genes, less than earlier estimates and closer to lower-order animals, such as mice and even roundworms. Genes contain DNA, the fundamental hereditary component of organisms, and are the blueprints for life. The DNA in the cell is known as the genome.
Nadeau, the James H. Jewell, M.D., MED '34 Professor in Genetics, contributed to the Science paper, which resulted from the privately funded research effort which the company Celera Genomics led.
Nadeau's name also appeared as the lead author on a paper in the same issue calling for a major research initiative to examine what the genes do, now that researchers know their sequences. That paper proposes an international consortium -- the International Mouse Mutagenesis Consortium -- to uncover the function of the human genes by studying the functions of genes in mice, which have roughly 3 billion "letters" in their code, approximately the same size as the human genome. The consortium has the early support of scientists at many of the world's leading research institutions.
The sequencing of the human genome and a nearly complete sequencing of the mouse genome has revealed that humans and mice share many of the same genes. "Because of the striking sequence similarities between humans and mice, discoveries in one species lead to strong inference in the other," Nadeau and his colleagues wrote.
Knowing the sequence is not enough, however. "Having the human genome sequence is like having someone hand you a bunch of computer disks and tell you, 'Here, these are great programs,' but without any further information, such as what the programs do and without instruction manuals," Nadeau said. "You're left to figure out what the programs do on your own." The consortium would like to find out what the programs are for the code represented in the human genes.
"Sequence analysis leads to no prediction of function for as many as 30 percent of the genes in the human genome, and the inferred functions of most of the remaining genes have yet to be proven," the researchers write. In an interview with the Plain Dealer, Nadeau said that finding the gene functions is "potentially a much bigger payoff. And much more relevant to human disease."
While we as humans may find it humbling to learn we have the same number of genes as mice, we can find some comfort knowing we are distinguished by a high proportion of large duplications in our genome compared with the sequenced genomes of the fly and the worm.
Eichler and Bailey did the analysis on segmental duplications in the publicly funded human genome sequence published in Nature, released simultaneously with the Science report. The National Institutes of Health funded this research.
Eichler, an assistant professor in genetics, and Bailey, a CWRU post-doctoral student, did their analysis on a supercomputer that they made from 30 personal computers linked together and operated with original computer code.
They found segmental duplications represent five to 10 percent of the genome.
"The amount of duplication is more than I think most scientists would have anticipated," said Eichler. "Five to 10 percent translates into about two chromosomes worth of DNA. This is a lot of territory."
He added, "What is more surprising than the amount, however, is the way this material is distributed. Most scientists believed ... [the] duplications would be restricted to clusters. What we have found is that these pieces have been mobilized to various regions of the human genome. This mosaic nature suggests that the genome is much more malleable or plastic than anticipated."
Eichler's laboratory will continue its work in sequence duplications.