Less than half of the more than 7,000 heritable diseases identified thus far have a known genetic origin. So, on 6 December, to help pinpoint the DNA glitches behind these disorders and thereby hasten diagnosis and drug development, the Bethesda, Maryland–based US National Human Genome Research Institute (NHGRI) and National Heart, Lung, and Blood Institute announced the funding of the Mendelian Disorders Genome Centers Program, part of a larger bundle of genomics grants totaling more than $400 million toward projects it has also supported in the past.

The nearly $50 million injected into the new Mendelian Disorders program over four years will go to four top genomics institutes in the US—the University of Washington in Seattle, Yale University in New Haven, Connecticut, and the joint genomics center from John Hopkins University in Baltimore, Maryland and the Baylor College of Medicine in Houston. These centers, which together already hold sequence data for around 12,000 individuals with more than 700 disorders, will add even more sequences, predominantly focusing on people's exons, the protein-encoding regions of the genome. The target diseases might run the gamut from more common diseases, such as heart muscle disorders, to rare diseases that only affect a few people, such as premature aging.

The center will sequence exons in lieu of full genomes because “a lot of the currently known Mendelian genetic variation is in the protein-coding regions,” says Lu Wang, head of large-scale sequencing at the NHGRI and director of the Mendelian Disorders Genome Centers. Exon sequencing is cheaper than whole-genome sequencing because only around 1–2% of the genome encodes protein. Given the costs of sequencing, it makes the most economic sense to start there, Wang explains.

Increasingly, given technological advances, scientists are advocating whole-genome sequencing over exome sequencing. Although the latter only contains one-fiftieth of the sequence length analyzed, about the cost saving is only half, at around $2,500 compared with $5,000 for the whole genome. This is because it is more expensive and labor intensive to process genetic material for exome sequencing, according to David Bentley, vice president and chief scientist of San Diego's Illumina, a leading sequencing company. Additionally, exon sequencing produces lower-quality data, which means researchers need more DNA samples—an issue with often-rare Mendelian diseases for which a few samples have to go a long way. “If you're talking about rare samples or blood drops from children, these samples are precious,” Bentley says.

Some scientists would rather see the Mendelian Disorders Genome Centers Program go after whole genomes from the get-go to capture the estimated 10% of genetic diseases that fall in the noncoding regions. “I wouldn't be surprised if the $1,000 genome does indeed happen next year,” says genomics veteran Orest Hurko, senior consultant at the Biologics Consulting Group, based in Alexandria, Virginia. “In that case, it's foolish to cut corners and just do the exons.”