Exome sequencing of health condition extremes can reveal susceptibility genes

(July 9, 2012)  Comparing the DNA from patients at the best and worst extremes of a health condition can reveal genes for resistance and susceptibility. This approach discovered rare variations in the DCTN4 gene among cystic fibrosis patients most prone to early, chronic airway infections.

The DCTN4 gene codes for dynactin 4. This protein is a component of a molecular motor that moves trouble-making microbes along a cellular conveyer belt into minuscule chemical vats, called lysosomes, for annihilation.

Similar “testing the extremes” strategies may have important applications in uncovering genetic factors behind other more common, traits, such as healthy and unhealthy hearts.

The results of the cystic fibrosis infection susceptibility study appear July 8 in Nature Genetics.  The infection in question was “Pseudomonas aeruginosa,” an opportunistic soil bacterium that commonly infects the lungs of people with cystic fibrosis and other airway-clogging disorders.  The bacteria can unite into a slithery, hard-to-treat biofilm that hampers breathing and harms lung tissue.  Chronic infections are linked to poor lung function and shorter lives among cystic fibrosis patients.  These bacteria rarely attack people with normal lungs and well-functioning immune systems.

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