Yale researchers identify new asthma genes

New research from Yale scientists has shown that asthma may be more complex than previously thought.

A few years ago, scientists focused on only two or three genes for asthma. Now about 250 genes are implicated.
A few years ago, scientists focused on only two or three genes for asthma. Now about 250 genes are implicated.

At the Yale Center for Perinatal, Pediatric and Environmental Epidemiology, School of Public Health professor Michael Bracken GRD ’74 designed several genetic studies to look for genes associated with increased susceptibility to asthma. Since there are already a few hundred genes linked to asthma, Bracken said he hopes the three newly identified genes may help doctors increase their understanding of how this common disease develops.

In the first study, School of Public Health professor Andrew DeWan analyzed the genetic makeup of 108 children in Connecticut and Massachusetts for 500,000 genetic markers. After sifting through the data, DeWan said he found one gene — associated with the muscle cells that line the lungs — that was different in asthmatic children.

In another study, researchers sifted through PubMed, a digital database run by the United States National Library of Medicine, for articles that cited genes associated with asthma. From a sample of 500 papers related to 250 genes linked to asthma, they culled the 50 most-researched genes and searched for them in the 108 children. While they found mutations on two of these genes in the children, only one gene involved in repairing double-stranded DNA had a particularly strong relationship with asthma.

The final study examined the average number of copies asthmatic children have of the TCR (gamma) gene, which codes for markers on the surface of immune system cells. Immune cells use these markers to recruit additional cells to kill foreign invaders such as pollen and dust, which asthmatic children are especially sensitive to. The researchers found that compared to non-asthmatic children, asthma sufferers had on average fewer copies of the TCR (gamma) gene, but they are not sure what this means yet, researcher Kyle Walsh GRD ’11 said.

Walsh said the difference in the number of copies is likely caused by mutations acquired after birth.

“If these are mutations you’re not born with, then you may be able to prevent people from getting them,” he said.

Bracken said these studies point to a new direction in asthma research. Only a few years ago, scientists were looking for just two or three genetic mutations that caused asthma. But as new studies have come out, Bracken said about 250 genes have been reported to be associated with asthma, with more to be discovered. In different combinations, these genetic mutations may interact together or with the environment to increase the risk of asthma, Bracken said. What was once believed to be a simple, chronic inflammatory lung disease, Bracken said, may instead have a whole spectrum of variants ranging from exercised-induced asthma to pollen-induced asthma.

Bracken said the next step is to determine how the pathways for asthma develop, which can lead to more effective treatments.

“The ultimate goal [is to] identify the child early,” he said.

Asthma affects more than 6.5 million children in the United States.

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