Researchers have pinpointed regions of the genome that contribute to the debilitating lung disease that is the hallmark of cystic fibrosis. The findings, published in the journal Nature Genetics, provide insight into the causes of the wide variation in lung disease severity experienced by CF patients. They also point to new diagnostic markers and therapeutic approaches for this and more common lung diseases such as COPD.

This study is among the first reported genome-wide scans of a single gene disorder. It was the work of the North American CF Gene Modifier Consortium, which brought together dozens of investigators from the United States and Canada to identify which regions of the genome are associated with lung disease severity in almost 3,500 CF patients.

Genome-wide association studies use “genechip” technology to identify genetic variants (single gene polymorphisms or “SNPs”) that could explain differences in health between individuals. The Consortium tested DNA from 2,464 CF patients, and then replicated their findings in another 973 patients. They also performed a separate genome-wide linkage scan, which looks at how gene variants are inherited through multiple affected families. All of their results pointed to the same two regions of the genome, one on chromosome 11 and one on chromosome 20.

Members of the consortium have now divvied up these chromosomal hotpots and are trying to understand how variants in these regions could underlie CF progression.

“The great expectation is that once we have a handle on a few key genes that contribute to the variation we see in the clinic then we have a great starting point to find mechanisms and biological pathways that may make good targets for treating lung disease,” said Fred Wright, PhD, one of the study’s authors and professor of biostatistics at the University of North Carolina at Chapel Hill School of Medicine.

Source: University of North Carolina at Chapel Hill School of Medicine