Personalized Medicine - Translational Informatics: Realizing the Promise of Knowledge-Driven Healthcare - page 46

The Beery twins' father was CIO at Life Technologies. Timothy McDaniel, Beth's
son, worked for Illumina. Though these stories give cause for optimism, we are still
a long way from widespread use of sequencing to guide clinical care.

3.4.4 Epigenetics

Epigenetics refers to functionally relevant, heritable changes to the genome that do
not involve changes to DNA sequence [ 33 ]. Some examples include DNA methyla-
tion (the addition of a methyl group to a specifi c site along the DNA molecule) or
modifi cation of histones, the proteins responsible for maintaining the 3D structure
of DNA in its coiled state in the nucleus. Much remains to be discovered about the
mechanisms of epigenetic phenomena, but links have been demonstrated to various
biomedical phenomena, such as aging [ 34 ] and oncogenesis [ 35 ]. It is likely that
epigenetic biomarkers will increasingly help to target therapies and interventions in
much the same way as the genomic biomarker signatures discussed above.

3.4.5 Gene/Environment Interaction

While genome-wide association studies have revealed a number of locations along
the genome that appear to play a role in various different diseases, rarely is the cor-
relation absolute. That is, a given genotype may be more common in people who
have a given disease than those who do not, but by no means does everyone with
that genotype develop the disease. Of course, many diseases are complex, with
numerous genes and pathways playing their respective roles. But even with identi-
cal twins who generally have the same genotype across all genes, one may become
sick while the other remains healthy.
It is important to note that genes do not manifest themselves in a vacuum. The
interactions between people's genes and the environment to which they are exposed
are critical in determining downstream phenotype. Take smoking as an example.
Different people's genotypes predispose them to the risk of cancer to varying degrees.
Within a set of identical twins, the genetic risk is essentially the same. However, if
one twin smokes regularly, and the other is a life-long non-smoker, the smoker is
far more likely to develop lung cancer. As another example, exposure to sunlight is
known to increase the risk of skin cancer. However, sun exposure is confers greater
risk for light skinned individuals than for dark skinned individuals. Recent work has
begun to uncover some molecular mechanisms underlying these gene-environment
observations. For example, in post-traumatic stress disorder (PTSD), it has been
shown that FKBP5, a stress response regulator, is more likely to be “demethyl-
ated” (i.e. the DNA is without a “methyl group” attached) in children exposed to
trauma. In this case, therefore, the underlying mechanism for this gene-environment