With Dr. Gourdine offering Functional Medicine at STA and her discussing
genomics and personalized medicine as part of Functional Medicine in our
staff meetings, I wanted to find out more about this topic. Fortunately,
Oxford University Press offers an excellent series of books called What
Everyone Needs to KnowR about various topics and one of them is entitled
Genomics and Personalized Medicine by Michael Snyder, Ph.D., the Stanford
Ascherman Professor, Chair of the Department of Genetics and Director of the
Center of Genomics and Personalized Medicine at Stanford University.
Let’s start by defining what genomics is. It is an area within genetics
that concerns the sequencing and analysis of an organism’s genome. We have
ten to thirty trillion cells in our bodies, differentiated into between 200
and 300 major categories. Each cell has the same DNA in its nucleus, a
polymer made up of four different nucleotide bases arranged in opposing
pairs on the two strands of the DNA wrapped in a double helix. The six
billion base pairs are distributed on the forty six chromosomes normally
found in human beings. This entire collection of six billion base pairs is
called the genome. Our genome contains about twenty thousand genes that
translate into RNA that codes for proteins and about another twenty thousand
genes that encode other types of RNA that are not made into proteins. Only
about two to three percent of our genome is accounted for by the
approximately forty thousand genes that encode into proteins and RNA. It is
likely that ten percent or more of our genome helps control the expression
of genes (i.e., turns them on or off) in various cell types in our bodies.
Small changes can occur in the DNA sequence. These are called structural
variations and can be deletions, insertions, duplications and inversions of
short sequences of base pairs. However, most differences that make people
differ from one another actually occur in the sequences that regulate gene
expression rather than in the protein-coding sequences themselves.
The first whole human genome sequence was completed in draft form in
2001 and in a more finished form in 2003. This was a composite prepared form
DNA samples from several individuals. With today’s technologies, it is now
possible to sequence an individual’s genome in a few days. A large scale
project called the “1000 Genomes Project” has determined the genome
sequences of more than one thousand people from diverse backgrounds and
regions around the world. More than fifty million variants have been found
in these sequences.
We all have a multitude of variants in our DNA. Methods have been
developed to analyze a person’s genome to find mutations that are predictive
of disease. Our DNA affects drug metabolism, side effects and drug-drug
interactions. So far, there have been several hundred identified genes that
affect a person’s response to a drug. Medicine becomes personalized when
genome sequencing reveals which variants of a gene a person has and how that
is related to how a person will respond to a specific drug. Analysis of the
genomes of a number of people revealed that a person’s genome sequence
typically has valuable information regarding about three to six drugs.
Variants of genes have been found that are predictive of differences in
sports performance and the likelihood of injuries while participating in
sports.
Our environment can influence our health by selectively turning certain
genes on or off, a process called epigenetics. Epigenetic changes refer to
stable, heritable changes in the expression of genes that occur without
alterations to the actual DNA sequence. Snyder states that it is likely that
epigenetic changes have an equal or even greater effect on our health than
genetic changes. DNA methylation occurs when one of the nucleotide bases,
cytosine, is directly modified by an enzyme that transfers a methyl group
onto the base. This modification affects whether or not various DNA regions
are accessible to be read and the corresponding genes expressed. DNA
methylation and gene expression can be affected by exercise and by aging.
DNA methylation has been implicated in the development and progression of
cancer.
Although our bodies are comprised of between ten and thirty trillion
cells, five to ten times as many cells live in and on us, primarily bacteria
but also fungi and other microorganisms. Most of these live in our small
intestine. We can contain up to three pounds of different types of bacteria
in us, which includes many hundreds to thousands of species. These species
contain ten million or more different genes. Each person’s microbiome is
unique. The latest throughput DNA sequencing technologies can be used to
identify these species. Depression, anxiety and autism have been linked to
differences in the microbiome.
I’ve covered a lot of ground in just a few paragraphs. Dr. Snyder does a
more extensive job in the book in case you want to expand your understanding
of these topics. If you want to pursue these issues as they relate to your
personal health, then contact the FXMED Center to begin this journey into a
better understanding of your health with Dr. Gourdine and Functional Medicine. Please call
855-696-9633.
