The authors therefore suggest that therapeutics targeting this pathway might provide a new approach to treating individuals with low-grade atrocytomas.

Analysis of the DNA of astrocytomas from a large number of children revealed that the most common genetic mutation was the duplication of a region of DNA containing the BRAF gene. Tumors with this genetic mutation showed signs of increased BRAF protein activity. Consistent with the idea that increased BRAF activity had a role in the development of the tumors, mutations in the BRAF gene that caused increased BRAF protein activity were detected in tumors that did not exhibit duplication of the region of DNA containing the BRAF gene. As pharmacologic and genetic silencing of the BRAF signaling pathway and the BRAF gene, respectively, prevented tumor cells from low-grade gliomas growing in culture, it was suggested that inhibiting the signaling pathway downstream of BRAF might be beneficial for individuals with low-grade atrocytomas.

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To see if these results could be generalized from the genetically isolated Hutterite population to a more diverse group, the researchers tested the same variations in the CHI3L1 gene in 178 Caucasian children enrolled in prospective birth cohort, known as COAST, a collaboration led by Robert Lemanske of the University of Wisconsin at Madison.

They also looked for correlations between asthma and SNP -131C/G in two clinical samples, one from the Children's University Hospital in Freiberg, Germany (344 children with asthma and 28, and 94 without), and one from the asthma clinics at the University of Chicago Medical Center (99 children and adults with asthma and 197 without).

In the two clinical samples, those with the CC configuration at position 131 were more likely to have asthma, with CG intermediate and GG the lowest risk of the disease. In the COAST cohort, many subject were still too young to have developed asthma, but the genetic patterns was closely associated with YKL-40 levels, and this association was already present at birth.

The authors suspect that the change from C to G at this site reduces expression of the gene, resulting in lower levels of YKL-40 and protection from asthma.

Although variation in CHI3L1 appears to be one of the most significant genetic triggers yet discovered for susceptibility to asthma, it is far from the sole cause of the disease, the researcher caution. In the Hutterites, it explains 9.4 percent of the variance in YKL-40 levels, suggesting that additional genetic variants also influence these levels. Finding those variations "could identify additional genes," they add, "with significant impact on asthma risk and lung function."

"This evolutionarily ancient pathway involving the innate immune system plays a surprisingly important role in asthma pathogenesis," said Ober, "and a single genetic variant in the CHI3L1 gene may account for most of this risk."

This could have a significant impact on drug development, she added. "For some people, if you block YKL-40 you might dramatically reduce the severity of the disease. Knowing the genotype at SNP -131C might identify those who most likely to benefit from such a treatment."

Asthma is a chronic, treatable disease that causes narrowing of the airways, making breathing difficult at times. More than 22 million people in the United States have asthma, including 6.5 million children under age 18, according to the Centers for Disease Control and Prevention (CDC). The disease generates annual health care costs estimated at $14 billion.

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