A collaboration between scientists at the National Human Genome Research Institute (NHGRI) and Boston University has developed a novel approach to identifying functional areas of the DNA molecule. By comparing different 3D shapes of a coiled DNA with similar shapes in other species, one can map out what a set of genes codes for without reading the base pairs themselves.
In their Science paper, the researchers compared the topography of the human genome with that of 36 other mammalian species, including mouse, rabbit, elephant and chimpanzee. Using this topographic approach, they found that about 12 percent of the non-coding DNA in the human genome appears to be functionally important — twice the amount detected using methods that simply compared DNA sequences.
What accounts for the difference? Researchers say DNA sequence is not always a good indicator of function. They found that very similar DNA sequences may assume very different topographical shapes, which can have a major impact on their function or lack of function. On the other hand, different DNA sequences may assume very similar topographical shapes and perform very similar functions. So, in many instances, DNA structure may be a better predictor of function than DNA sequence.
The researchers went on to mine data organized by the PhenCode Project to see whether one-base variations in DNA sequence, called single-nucleotide polymorphisms (SNPs), in non-coding regions can cause structural changes that might lead to disease. Specifically, they conducted a topographic survey of 734 non-coding SNPs known to be associated with signs and symptoms of disease. The non-coding SNPs associated with disease tended to produce larger changes in the shape of DNA than a set of SNPs not linked to disease.
Press release: Researchers Devise New Way to Explore DNA