It is reasonable to assume that genetic risk variants will lead to markers for earlier detection of CAD as well as drug therapies to interrupt or attenuate the risk. This is occurring along with the overall trend of personalized medicine, in which the disease and the individual will be treated with more specific therapies to match their selleck products Genome susceptibilities. Funding Statement Funding/Support: Dr. Roberts receives grant support from CIHR#MOP82810 (RR)/Canada and CFI#11966
(RR)/Canada. Footnotes Conflict of Interest Disclosure: Dr. Roberts is a consultant to Cumberland Pharmaceuticals and Celera.
Basic Structure of the Human Genome The human Inhibitors,research,lifescience,medical genome, a diploid genome, is comprised of 3.2 billion nucleotides that are packed into 23 pairs of chromosomes. It contains approximately 23,500 protein-coding genes. Each gene is comprised of the protein-coding segments, known as exons; the intervening sequences, known as introns; Inhibitors,research,lifescience,medical and the regulatory regions on each end of the gene (5’ and 3’ end regions). There are about 180,000 exons in each human genome that are collectively referred to as an
exome. Since the exome occupies only about 1% of the genome, the size of an exome is roughly 30 million nucleotides; thus, approximately 99% of the human genome does not code for a protein. However, these regions by and large have biological Inhibitors,research,lifescience,medical functions that might affect gene expression and likely the clinical phenotypes. The current focus in medical sequencing is on the exome, as approximately three-quarters of the known pathogenic
variants affect the protein-coding exons. The Enabling Effects of “Disruptive” Sequencing Technologies The high throughput DNA sequencing technologies have dramatically changed Inhibitors,research,lifescience,medical the landscape of genetic discoveries. The conventional technique of genetic linkage Inhibitors,research,lifescience,medical analysis in large families followed by sequencing, using the Sanger technique, of the genes residing at the mapped locus has all but been replaced with the new technologies, wherein millions of DNA fragments are sequenced simultaneously and in parallel. These high throughput sequencing (HTS) approaches have increased the output of a single sequencing reaction by several orders Dacomitinib of magnitude, enabling sequencing of the entire human genome and a dozen exomes in a week. The enormity of these “disruptive” technologies is best illustrated by the fact that the initial sequencing of the human genome through the Human Genome Project took more than a decade, selleck chemicals involved multiple sequencing centers, and cost approximately $3 billion.1 Today, the entire human genome could be sequenced in a small laboratory at a cost of less than $10,000 and an exome at the cost of about $1,000. Despite these technical feats, the enormous size of the sequence readout and the complex genetic diversity of humans pose major challenges in applying whole genome sequencing and even whole exome sequencing (WES) at the bedside.