Their study appears in a recent issue of Genome Research.
The statistical method is significant because when researchers announce they have sequenced an organism's genome, they really mean that they have created a mosaic of two chromosomes, said USC computational biologist Lei Li.
"A mosaic means it's not real," Li said.
Lead author and former graduate student Jong Hyun Kim, advised by Li and USC University Professor Michael Waterman, was able to infer a complete sequence of the chromosomes of Ciona intestinalis, a marine invertebrate, from existing sequencing data.
Kim's method exploited the high rate of genetic mutations in the organism. Other organisms with high genetic variability, such as certain fish, also may be suitable.
Because the human genome has a relatively low mutation rate, the method cannot be applied to people.
However, Kim said, the method might be useful in sequencing parts of the human genome that display high variability.
As a by-product of their analysis, the researchers added to growing evidence that so-called junk DNA may have a function after all.
Recent studies have shown that junk DNA expresses proteins which may regulate gene function, and that sections of junk DNA have been highly conserved during evolution, suggesting that they play an important role.
The Genome Research study confirms that many short sections of junk DNA are highly conserved, Li and Kim said.
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"While these are preliminary findings that require replication in larger studies, we would argue that this may explain part of the variance among women in the susceptibility to developing this mood disorder," Rubinow said. "Studies have shown that PMDD is characterized by abnormal sensitivity to reproductive steroids like estrogen. As a receptor for the hormone that can trigger the onset of PMDD symptoms, ESR1 has clear physiologic relevance for this disorder."
The authors acknowledge that as with other complex genetic disorders, the contribution to PMDD of polymorphisms in a single gene may not be large. In addition, they also noted that the findings may be telling us more about the control group.
These women, who have no history of psychiatric problems or menstrual cycle-related symptoms, may have gene variants that protect against PMDD. According to Rubinow, "this is equally interesting because it may help us to understand resilience and protection, which are also very important."
Dr. Susan S. Girdler, professor of psychiatry and director of the UNC Psychiatry Stress and Health Research Program, pointed out that the severity of PMDD symptoms are as great or can be as great as those of women with full-blown major depression or major anxiety disorder. "But what makes them different is that the symptoms are very time-limited and linked strongly with the women's menstrual cycle."
Girdler emphasizes that to qualify for PMDD, symptoms must be severe enough to interfere with everyday functioning - to disrupt relationships, result in social withdrawal, even prompt thoughts of suicide. "We are talking about women who meet very stringent diagnostic criteria for PMDD. This is not the garden variety PMS."
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