THURSDAY, Jan. 13, 2005 (HealthDayNews) -- Researchers are rewriting the rules for human genetics, and their findings have medical implications for conditions ranging from diabetes to cancer to heart disease.
Going out the window is the untouchable "one gene-one protein" rule, which said that a single gene makes only one protein. It's gone because of the discovery of a process called alternative splicing, in which a single gene can make many different proteins.
A protein is a chain of molecules called amino acids. Genes carry the code for production of those amino acids, which are strung together to form the proteins that not only form the body's structure but also carry out the biochemical processes necessary for life.
Alternative splicing means that a gene does not produce a single chain of amino acids. Instead, it can produce a number of subchains that can be linked in different ways to form different proteins.
That discovery has helped solved one of the biggest puzzles about the human genome -- why people have so few genes.
Biologists originally thought the complex human organism required at least 50,000 genes. That was revised downward to no more than 30,000 as data from the Human Genome Project became available. The latest estimate is in the neighborhood of 20,000 genes -- about the same number as a decidedly simplistic worm.
The idea of alternative splicing to explain the low number of human genes arose with the new century, said Dr. Xiao-Feng Yang, an assistant professor of medicine and immunology at Baylor College of Medicine, and a leader in the field.
Yang and his colleagues have been examining the role of alternative splicing in such autoimmune diseases as rheumatoid arthritis and type 1 diabetes, in which the body's immune system mistakenly attacks its own tissue.
In a recent report in the Journal of Allergy and Clinical Immunology, Yang and his colleagues compared 45 proteins associated with autoimmune disease with 9,554 proteins randomly selected from the human genome.
They found that alternative splicing within specific regions occurred in all of the proteins called autoantigens, which elicit an attack from the immune system. Alternative splicing was found in only 42 percent of the randomly selected proteins.
"When these isoforms [different protein forms] get above a threshold of difference, immune tolerance to self-proteins breaks down," Yang said. "The immune system starts to attack the proteins and the cells in which they are found."
And a report in the Jan. 14 issue of Cell, researchers at the University of California, San Diego (UCSD), said that alternative splicing could play a role in heart disease.
The researchers studied a protein designated ASF/SF2, which regulates a calcium enzyme responsible for heart contraction and tissue growth.
ASF/SF2 is part of a family of proteins that function in alternative splicing. Mice born with mutated or absent ASF/SF2 had hearts that could not contract properly, and they died young.
The finding "may provide insights into mechanisms that directly contribute to heart attacks in humans," study author Xiang-Dong Fu, a professor of cellular and molecular medicine at UCSD, said in a statement.
Alternative splicing also appears to play a role in muscular dystrophy, said Dr. Thomas A. Cooper, a professor of pathology at Baylor, who wrote a commentary on the Cell report. In myotonic dystrophy, the most common form of the condition, "misregulation of alternative splicing is the most common cause," Cooper said.
Basic science could someday lead to better treatment, Yang added.
"There is a potential for a therapeutic effect," he said. "You could find a way to block the troubling form of the protein or to block the immune system's response to it."
A basic guide to medical genetics is provided by the National Library of Medicine.