Searching for the soul of the genome

The discovery that a ''gene desert'' on chromosome 9 was a hotspot for coronary artery disease (CAD) risk was among the highlights of findings produced recently by genome-wide association studies, which compare the genomes of many people for genetic variations and have been broadly used in the past few years to study hundreds of diseases and complex traits. Gene deserts are large genomic segments devoid of genes.

Now scientists at the University of California, San Diego School of Medicine and colleagues have developed a novel approach to detect long-distance chromosomal interactions and have applied this method to the chromosome 9 gene desert, revealing that the association results from an altered inflammatory signaling response in individuals with increased CAD risk.

The findings are published in the Feb. 10 issue of Nature.

The researchers followed up on results of the widely reported genome-wide association studies in 2007 and 2008, noting that the gene desert interval on chromosome 9 contained DNA variants (called single nucleotide polymorphisms or SNPs) associated with CAD and type 2 diabetes mellitus (T2D). Based on these findings, Francis Collins, director of the National Institutes of Health and a leader in the original Human Genome Project, publicly described the chromosome 9 interval as ''like the seat of the soul of the genome.''

The DNA variants associated with CAD and T2D are located close to one another on chromosome 9, but inherited independently so genetic risk for developing CAD is not associated with risk for the T2D.

In comparing the genomes of people with heart disease and people without, Frazer and colleagues found that those who carried the chromosome 9 DNA risk variants for CAD had a two-fold higher risk of early onset myocardial infarction (a heart attack) than non-carriers.