CROSS COMPARE: Each model organism has its own vocabulary that researchers use to describe an array of characteristics. The Monarch Initiative has mapped phenotype descriptions used in model systems to human clinical features. The Initiative’s Exomiser software employs this mapping strategy to help users better understand human genetic disorders by widening the pool of gene-function associations.ROBINSON ET AL., GENOME RES, 24:340–48, 2014. Last fall, the conclusion of the 1000 Genomes Project revealed 88 million variants in the human genome. What most of them mean for human health is unclear. Of the known associations between a genetic variant and disease, many are still tenuous at best. How can scientists determine which genes or genetic variants are truly detrimental?
Patients with rare diseases are often caught in the crosshairs of this uncertainty. By the time they have their genome, or portions of it, sequenced, they’ve endured countless physician visits and tests. Sequencing provides some hope for an answer, but the process of uncovering causal variants on which to build a treatment plan is still one of painstaking detective work with many false leads. Even variants that are known to be harmful show no effects in some individuals who harbor them, says Adrian Liston, a translational immunologist at the University of Leuven in Belgium who works on disease gene discovery.
Exome sequencing, which covers the 1 percent to 2 percent of the genome that codes for protein, typically turns up some 30,000 genetic variants, which ...
