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In 1909, almost half a century after Gregor Mendel’s experiments that defined the principles of genetic inheritance, Danish botanist Wilhelm Johannsen coined the term gene to describe the basic functional unit of heredity (Mendel, 1866; Johannsen, 1909). Less than half a century later, the 1953 discovery of the DNA double helix by James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin, represented one of the most significant advances in the biomedical world (Watson & Crick, 1953; Maddox, 2003). Two additional landmark moments occurred in February 2001, when the initial draft sequences of the human genome were published (Lander et al., 2001; Venter et al., 2001), and in April 2003, when the International Human Genome Sequencing Consortium reported the completion of the Human Genome Project, a massive international collaborative endeavor that started in 1990 and is thought to represent the most ambitious undertaking in the history of biology (Collins et al., 2003; Thangadurai, 2004; National Human Genome Research Institute, http://www.genome.gov). The Human Genome Project provided a plethora of information about specific genes, and the genome, that significantly changed our perspectives on the biomedical and social sciences. The sequencing of the first human genome, a 13-year, 2.7-billion-dollar effort, relied on the automated Sanger (dideoxy or chain termination) method, which was developed in 1977, around the same time as the Maxam-Gilbert (chemical) sequencing, and subsequently became the most frequently used approach for several decades (Sanger & Coulson, 1975; Maxam & Gilbert, 1977; Sanger, Nicklen, & Coulson, 1977). The new generations of DNA sequencing technologies, known as next-generation (second generation) and next-next-generation (third generation) sequencing, which started to emerge commercially in 2005, enabled large chromosomal regions to be sequenced during progressively shorter time frames and at lower costs and, in addition, facilitated the emergence of additional, even more sophisticated applications, such as single-cell genomic sequencing (Service, 2006; Blow, 2008; Morozova & Marra, 2008; Metzker, 2010). While $10 allowed the sequencing of a single base in 1985, approximately 10,000 bases were sequenced, at the same cost, two decades later (Shendure, Mitra, Varma, & Church, 2004; Pettersson, Lundeberg, & Ahmadian, 2009). Over 100 million base pairs can now be sequenced, in 200-400 base-pair fragments, in as little as 4 hours. As a result of these advances, it took only two months in 2008, and less than 1 million dollars, to sequence a diploid human genome, that of James Watson (Wheeler et al., 2008; Imelfort, Batley, Grimmond, & Edwards, 2009). All these developments promise to bring the $1,000 genome goal, an important milestone of personalized medicine, closer to reality.
The Human Genome Project revealed that the genome encodes 20,000-25,000 genes, less than 50,000-100,000, the number predicted a few years earlier (Fields, Adams, White, & Venter, 1994; International Human Genome Sequencing Consortium, 2004). As a result of gene-disease and gene-phenotype connections that are continually unveiled, genetic testing has witnessed an unprecedented development.