6
Molecular Biological Basis of Personalized Medicine
Although several factors are involved in the development of personalized medicine,
developments in molecular biology have played an important role. Some basic
terms are defi ned briefl y in this section.
The Human Genome
The total genetic material of an organism, that is, an organism’s complete DNA
sequence is called a genome. The human genome is extremely complex, and the
estimated number of genes has varied considerably during the past years. GENCODE
19 contained 20,719 protein-coding genes. A study has mapped peptides detected in
seven large-scale proteomics studies to ~60 % of the protein-coding genes in the
GENCODE annotation of the human genome (Ezkurdia et al. 2014 ). The investiga-
tors described a set of 2,001 potential non-coding genes based on features such as
weak conservation, a lack of protein features, or ambiguous annotations from major
databases. Peptides were identifi ed for only 3 % of these genes. Most of these genes
behave like non-coding genes rather than protein-coding genes and are unlikely to
code for proteins under normal circumstances. If one excludes them from the human
protein-coding gene catalog, the total number of genes in the human genome is
reduced to ~19,000.
ENCODE
Following sequencing of the human genome in 2001, the aim of ENCODE
(ENCyclopedia Of DNA Elements) became description of all functional elements
encoded in the human genome (nature.com/encode). The federal project involved
440 scientists from 32 laboratories around the world. Nine years after launch, its
main efforts culminate in the publication of 30 coordinated papers (Skipper et al.
2012 ). Collectively, the papers describe 1,640 data sets generated across 147 differ-
ent cell types. Among the many important results there is one that stands out above
them all: more than 80 % of the human genome’s components have now been
assigned at least one biochemical function. ENCODE fi ndings have implications for
many fi elds in biology. Some key fi ndings are:
The human genome has at least four million gene switches that reside in bits of
DNA that once were dismissed as “junk DNA” but that turns out to play critical
roles in controlling how cells, organs and other tissues behave. At least 80 % of this
DNA is needed for normal function and is active. Human DNA is a very long
strand – 3 m of DNA stuffed into a microscopic nucleus of a cell − that it fi ts only
because it is tightly wound and coiled around itself and is referred to as a “hairball
with a 3D structure. In the past, when only the uncoiled length of DNA was analyzed,
1 Basic Aspects