Scientists have long studied the process of meiosis, the type of cell division that produces egg and sperm cells. But a full understanding of the process, which is known to play a key role in causing birth defects such as Down syndrome, has remained elusive.
Led by Michael Dresser, M.D., Ph.D., a team of scientists from the Oklahoma Medical Research Foundation last year discovered a new process in meiosis that appears to help prevent formation of abnormal chromosomes. Now, in a paper in the new issue of the journal Cell, the OMRF researchers have shed important new light on this process in which parts of the chromosomes act as a sort of cellular police force.
“These findings can help blaze a new path for understanding how cells keep their chromosomes intact and avoid generating genetic diseases,” said Dresser.
Meiosis is a central part of the reproductive process. In meiosis, 46 chromosomes come together, then are sorted into 23 pairs, ensuring that each sperm and egg contains the proper number of chromosomes.
At OMRF, Dresser’s research team, which also consists of Michael Conrad, Ph.D., Emma Lee and Anton Konovchenko, discovered a process in meiosis that helps prevent formation of abnormal chromosomes. Using high-powered microscopy to study cell division, the scientists found that structures (known as telomeres) at the ends of chromosomes act as genetic law enforcement officers, pulling apart chromosomes that are not supposed to interact.
The new research in Cell, which was done in collaboration with OMRF microscopy expert José Conchello, Ph.D., now reveals that this process is controlled by a set of rapid movements that tests the strength of the bonds between chromosomes.
“These movements snap the bad connections between chromosomes, ensuring that they won’t give rise to disease or abnormalities,” said Dresser. “They also regulate good connections, strengthening proper pairings between chromosomes. So you can look at these movements as a cellular line-up process, where authorities try to sort out the bad couplings from good ones.”
The research was performed in yeast. “Many of the genes required for this process are similar in yeast and humans, so there is a clear avenue for applying these findings to questions of human health and disease,” said Dresser.
For example, scientists have long known that inheriting the wrong number of chromosomes can give rise to Down syndrome. More recently, researchers have discovered that children frequently inherit chromosomes with small bits that either are extra or missing, deficiencies that can be related to health problems such as autism.
Going forward, the OMRF researchers will study how the newly discovered meiotic process could play a role in causing—and, hopefully, preventing—chromosomal defects. “Now we have a new place to look when we try to understand situations where abnormal chromosomes are generated too frequently,” said Dresser. “Our goal will be to identify genetic or environmental factors that interfere with this process.”
This basic knowledge, said OMRF President Stephen Prescott, M.D., could ultimately lead to new methods for prevention of birth defects and the serious health problems they give rise to.
“For more than a century, researchers have focused on how chromosomes get together,” said Prescott. “Dr. Dresser, though, decided to look at the problem differently, and ask, ‘How do chromosomes not get together? How do they avoid making wrong connections?’
“As is so often the case in science, looking at the problem from a new and unexpected vantage point has produced exciting results,” continued Prescott. “We hope that these findings will one day lead to new weapons in the battle against birth defects and genetic disease.”
Dresser is an associate member of OMRF’s Cell Cycle and Cancer Biology Research Program. He earned his B.A., M.D. and Ph.D. degrees from Duke University and joined OMRF’s scientific staff in 1989. His research focuses on chromosomal abnormalities that arise during the development of sperm and eggs.
Chartered in 1946, OMRF (www.omrf.org) is an independent, nonprofit biomedical research institute dedicated to understanding and developing more effective treatments for human disease. Its scientists focus on such critical research areas as Alzheimer’s, heart disease, cancer and children’s diseases.