To demonstrate the utility of their approach, researchers focused on the exomes of eight people (four Yoruba, two East Asians, two European-Americans), whose DNA had previously been characterized by the International HapMap Project. The HapMap Project was an effort that produced a comprehensive catalog of common human genetic variation across the human genome. In addition, the study included four unrelated people with Freeman-Sheldon syndrome, a rare inherited disorder caused by mutations in the MYH3 gene, to see if exome sequencing had the power to detect the MYH3 mutations known to exist in their DNA.
The researchers began by shearing the 12 samples of genomic DNA into fragments and then using special probes to capture only those fragments that contained exons. The resulting 12 collections of exomes, were then sequenced and analyzed. Altogether, the project determined 300 million bases of DNA sequence the largest data set reported so far of human coding sequence produced by more advanced second-generation sequencing technologies.
Comparison of the exome sequences to the publicly available human genome sequence highlighted the sensitivity of this technique for detecting genetic variations, both common and rare. The investigators were able to identify a range of these DNA misspellings, such as rare and common single letter variations known as single nucleotide polymorphisms, or SNPs, and insertions and deletions of sequences within genes.
From the DNA of the four people with Freeman-Sheldon syndrome, the researche
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