Kansas City, Mo. (Sept. 1, 2006) – Scott Hawley, Ph.D., Investigator, and Youbin Xiang, Ph.D., Research Specialist, have published findings in today’s 90-year anniversary issue of the journal Genetics, that resolve a mystery first presented in the journal’s premier issue in 1916.

     In that issue, Calvin Bridges published “Nondisjunction as proof of the chromosome theory in heredity.” In addition to proving that genes map on chromosomes, and that mistakes in the segregation of chromosomes results in the aberrant transmission of genes, the paper presented a mystery.

     When one crosses appropriately marked XY males to XX females, one in every 2,000 occurrences results in an XXY female, a disorder known as primary nondisjunction. If you take those XXY daughters and cross them back to XY males, the frequency of nondisjunction rises nearly one-hundred fold to one in 20, and the phenomenon is known as secondary nondisjunction.

     What caused this dramatic rise in nondisjunction? Bridges offered an explanation that was quickly disproved, and it wasn’t until 1948 that researcher Kenneth Cooper offered an alternative, albeit speculative, explanation that those X chromosomes that failed to pair and recombine with each other would then couple with the Y in mid-prophase to form a trivalent (the Y is metacentric and the Xs are acrocentric). The Y would then direct the Xs to the opposite pole of the developing spindle resulting in XX<->Y segregation.

     Cooper went on to a distinguished career in genetics that included teaching chromosome biology at the University of California, Riverside. His theory of secondary nondisjunction remained the dominant one for nearly six decades, even though it had never been tested.

     This year, just in time for the 90th anniversary issue of Genetics, one of Cooper’s former UC Riverside students, Dr. Hawley, put Cooper’s theory to the test.

     “What we found was that although Cooper was right about the trivalent, he was wrong about how it was formed, and he was wrong in a very important way,” said Dr. Hawley. “It turns out that the XXY trivalent is there from the very beginning of prophase. If the Xs fail to crossover, the trivalent is maintained. But if the two Xs do crossover, they dissociate themselves from the Y chromosome and form a monogamous bivalent.”

     “The good news is, we’ve resolved the fascinating nondisjunction problem posed by Bridges 90 years ago,” said Dr. Hawley, “and the better news is that in doing so, we’ve opened a whole new venue of research and uncovered so many new questions to answer.”

     “Secondary nondisjunction has been interesting to geneticists over decades because of its central importance to dissecting meiotic mechanism in Drosophila,” said Dr. Xiang. "Although several models have been proposed, they have never been directly tested until now, so it has been really exciting to be involved.”

     “It is a great honor for Dr. Hawley and for the Institute that his findings resolving the question of secondary nondisjunction will appear in the 90th-anniversary edition of Genetics,” said Robb Krumlauf, Ph.D., Scientific Director. “He has contributed so much to the field of genetics — both as researcher and a teacher. I can think of no one better to revisit Dr. Bridges’ 1916 findings.”

About the Stowers Institute
     Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.