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Johns Hopkins researchers uncover genes at fault for cystic fibrosis-related intestinal obstruction
Date:4/23/2012

teract with a nearby cell membrane protein than with a protein that's deep inside the cell. They tested DNA samples from 3,763 CF patients611 who had had MI and 3152 who hadn'tto compare genes that encode for cell membrane proteins to those that encode for unrelated proteins. Three of the 155 genes tested that encode for cell membrane proteins correlated with risk for MI, compared with none of the 231 genes tested that encode for unrelated proteins.

"These genes have common variants that all of us happen to be carrying around," says Cutting, "and just by chance, if you have a child with CF, these common variants play a role in modifying risk for meconium ileus." The researchers wanted to look for additional gene variants associated with an increased risk for MI, using a different approach.

In an earlier study, Cutting's team had found a region of human chromosome 8 to be linked to MI. To pinpoint which gene within that region leads to the condition, the researchers analyzed the DNA of 133 families with at least two CF children, at least one of whom previously had MI. The DNA was tested to determine which parts of chromosome 8 parents had passed down to their children who had MI.

Using this approach, the researchers found variants of the methionine sulfoxide reductase (MSRA) genein this case, a particular combination of DNA alterations close to and within the genethat appeared significantly more often in children who had MI. In an unrelated CF patient population from Canada, they found evidence of the same link between MSRA and MI, which helped confirm their results.

While the researchers now knew that CF patients with a certain MSRA gene variant tended to have had MI as newborns, they didn't yet know whether MSRA actually plays a role in MI and hence whether it is truly a modifier gene. To address this question, they turned to mice engineered to have CF that tend to die from intestinal obstruction and developed three geneticall
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

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