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Identifying the Genomic Basis of Biological Variation: Determining the DNA Sequence of a Genome

By Diane P. Genereux

Determining the DNA Sequence of a Genome

The first efforts at sequencing an organism—discovering the specific sequence of nucleotides, or chemical building blocks, that constitute the entire genetic makeup of an individual—occurred during the 1970s. The focus was not, however, on the human genome. Instead, initial studies focused on bacteriophages, viruses that can infect bacterial cells, whose genomes are often as small as 0.000015 times the size of a human genome. Some twenty years later, the Human Genome project determined the sequence of a full human genome using “Sanger sequencing,” a method that reads a genome in very small segments, which researchers must then piece together. Sequencing advances in recent decades have largely focused on increasing the size of these reads (thereby reducing the challenge of joining them post facto), increasing the speed of sequencing, and reducing costs. Together, these advances have enabled collection of genome data from some thirty million individual humans. In “The Sequence of Sequencers,” James Heather and Benjamin Chain review the history of sequencing techniques, emphasizing the rapid growth of capacity from sequencing the first small bacteriophage genome to the ability to sequence the much larger genomes of individual humans in large numbers. More recently, Alexis Burian and colleagues, in “Genome Sequencing Guide,” and Muhammad Tariq Pervez and his group, in “A Comprehensive Review of Performance of Next-Generation Sequencing Platforms,” provide more technically detailed accounts of contemporary technologies, including their relative strengths, error rates, and costs