Industrial Scale Genome Sequencing to Uncover Multifactorial Diseases

January 29, 2016

In my book on epigenetics, I discussed the problems of investigating diseases with a multifactorial basis, that is, conditions in which many genes determine a condition, such as cardiovascular disease. I argued that because a thousand or more genes may be involved, and each makes a small contribution to the phenotype, and because environmental influences play a role in such gene expression, it is very difficult or perhaps impossible to isolate individual genes and their allelic variants that are responsible for the condition.

Apparently the NIH got my message, because a consortium of four institutions have formed the Centers for Common Disease Genomics, to be funded by a $200 million grant to sequence and analyse thousands of genomes from a large and diverse population. The four  institutions chosen to receive the funding will employ the latest technology which was not available at the time (2013) that I researched my book. These sequencing machines, the Hi Seq X, were released last year and developed specifically for large-scale studies. The machines – at cost of $1 million each — are sold only in groups of 10. Combined with advanced analytical computer power, the will compare the genome on individuals with the disease and healthy controls.

This high stakes game of genetic analysis represents an entirely new level of complexity, and may require intellectual and technical breakthroughs that are not yet invented. It will require ways of ensuring that environmental variation be factored out so it does not swamp out the contribution due to genetic input, which may be quite small for each individual gene. It also will require methodology for coallating genetic and epigenetic variation, which is known to substantial. Finally, the finding must point the way to therapies that will be substantial and meaningful in their effect upon the affected individuals.

It will be of great interest to follow how this technology unfolds in the coming years.

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