on February 4th, 2016 No Comments
As whole-genome sequencing gains ground, researchers and clinicians are struggling with how best to interpret the results to improve patient care. After all, three billion base pairs are a lot to sift through, even with powerful computers. Now genomicist Gill Bejerano, PhD, and research associate Harendra Guturu, PhD, have published in PLoS Computational Biology the results of a study showing that computer algorithms and tools previously developed in the Bejerano lab (including one I’ve previously written about here called GREAT) can help researchers home in on important regulatory regions and predict which are likely to contribute to disease.
When they tried their technique on five people who agreed to publicly share their genome sequences and medical histories, they found it to be surprisingly prescient. From our release:
Using this approach to study the genomes of the five individuals, Guturu, Bejerano and their colleagues found that one of the individuals who had a family history of sudden cardiac death had a surprising accumulation of variants associated with “abnormal cardiac output”; another with hypertension had variants likely to affect genes involved in circulating sodium levels; and another with narcolepsy had variants affecting parasympathetic nervous system development. In all five cases, GREAT reported results that jibed with what was known about that individual’s self-reported medical history, and that were rarely seen in the more than 1,000 other genomes used as controls.
Bejerano and Guturu focused on a subset of regulatory regions that control gene expression. As I explained:
The researchers focused their analyses on a relatively small proportion of each person’s genome — the sequences of regulatory regions that have been faithfully conserved among many species over millions of years of evolution. Proteins called transcription factors bind to regulatory regions to control when, where and how genes are expressed. Some regulatory regions have evolved to generate species-specific differences — for example, mutating in a way that changes the expression of a gene involved in foot anatomy in humans — while other regions have stayed mostly the same for millennia. […]
All of us have some natural variation in our genome, accumulated through botched DNA replication, chemical mutation and simple errors that arise when each cell tries to successfully copy 3 billion nucleotides prior to each cell division. When these errors occur in our sperm or egg cells, they are passed to our children and perhaps grandchildren. These variations, called polymorphisms, are usually, but not always, harmless.