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Pitt team finds protein that sets the stage for exchanges of DNA code in eggs and sperm

A team led by a scientist at the University of Pittsburgh School of Medicine has discovered a regulatory protein that influences where genetic material gets swapped between maternal and paternal chromosomes during the process of creating eggs and sperm. The findings, which shed light on the roots of chromosomal errors and gene diversity, appear in tomorrow's issue of Nature.

Most cells contain 46 chromosomes, half coming from each parent. But eggs and sperm, known as germ cells, have half as many so that when they combine to form an embryo, the correct chromosome number is maintained, explained senior author Judith Yanowitz, Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences, Pitt School of Medicine, a member of the Magee-Womens Research Institute, and former staff associate at the Carnegie Institution of Washington, Baltimore.

"When germ cells form, segments of DNA are exchanged, or recombined, between maternal and paternal chromosomes, leading to greater diversity in the daughter cells," she said. "Our research reveals a protein that plays a key role in choosing where those crossovers occur."

Crossing over is essential for the correct movement, or segregation, of chromosomes into the germ cells. Failure to exchange DNA properly can lead to offspring with the wrong number of chromosomes and, in humans, defects in this process are a leading cause of infertility, Dr. Yanowitz noted.

Despite the importance of this process for development, little is known about the factors that influence where crossovers occur and how they are regulated. In the genome of the tiny round worm C. elegans that the researchers studied, gene recombination typically occurs toward the ends of the chromosomes, which contains fewer genes.

But the "crossover landscape," as Dr. Yanowitz calls it, changed in two ways in worms that had a mutation in a protein called X non-disjunction factor (xnd-1): crossovers instead occurred in the gene-rich, central areas of the chromosomes; and crossovers on the X chromosome often did not occur.

"This is the first gene in any system that is specifically required for the segregation of single chromosomes," she said. "The fact that this is the X chromosome is interesting because the sex chromosomes play a unique role both in germ line and general development."

These observations led the researchers to suggest that xnd-1affects the way chromosomes are packaged into the nucleus of the cell as a DNA protein complex known as chromatin. They further showed xnd-1 alters a component of chromatin that has been maintained through species evolution and that this packaging is directly responsible for the effects on crossover formation.

Cynthia R. Wagner, Ph.D., of the Carnegie Institution of Washington; and Lynette Kuervers, Ph.D., and David Baillie, Ph.D., of Simon Fraser University in British Columbia, Canada, co-authored the paper.

The research was funded by the National Institutes of Health, Magee-Womens Research Institute, and the Carnegie Institution of Washington.

About Magee-Womens Research Institute

Magee-Womens Research Institute (MWRI), established in 1992, is devoted exclusively to the health concerns of women and infants. Today, the Institute is the largest women's health research facility in the country, conducting research that spans a woman's entire life cycle – from the formation of cells and embryos through pregnancy, menopause and late life.

Since its inception, the Institute has become a well-recognized and respected center for its research, both nationally and internationally.

Now in its second decade, it has grown from approximately 20 faculty members to more than 90 faculty members who have broad experience in numerous aspects of female physiology and biology. Dedicated to basic, translational, and clinical research in women and infants' health, this diverse group of basic and clinical scientists collaborates on research studies and the practical application of their findings. MWRI's interactive approach to research, affiliation with the University of Pittsburgh, and location (only steps away from Magee-Womens Hospital of UPMC's large clinical patient volume) uniquely positions MWRI as an ideal center for reproductive sciences research.

About the University of Pittsburgh School of Medicine

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to NIH data for 2008 (the most recent year for which the data are final).

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see

Anita Srikameswaran | EurekAlert!
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