In May 2016, in a short eight-page report in Nature
Biotechnology, Rong Chen, Stephen Friend and Eric Schadt from the Icahn School
of Medicine at Mount Sinai, New York, and their colleagues reversed our ideas
about genetic determinism. This small revolution proved to be radical because
by association, this also unhinges biological determinism—the belief that biology
determines all your traits.
What they did is to apply scientific methods to commonly
held beliefs about disease. Usually genetic investigations focus on a group
with disease by trying to find genes that are different in this group from the
rest of the population. By comparing this group with a control group they hope
to single out the gene that causes this difference. Sometimes geneticists hit
lucky and find only one gene that is different between the two groups. In such
circumstances this single gene follows Mendelian laws in how it affects people.
Mendelian laws are named after the monk Gregor Johann Mendel.
Between 1856 and 1863--before genes were discovered in the
early 1900s--Mendel was working on cultivating some 29,000 pea plants. He noticed
that peas seem to acquire their characteristics from both parents in a
mathematical fashion, with some traits being more dominant than others. Mendel discovered
the mathematics of heritability.
He defined for every characteristic—a phenotype, an
expressed genetic trait—there are two parts determining how that characteristic
is expressed. Now we know that two alleles compose a gene that determine a
physical trait. Mendel’s observations developed three basic laws:
·
Alleles can be either dominant or recessive,
with the dominant allele always imposing its influence over the recessive.
·
Alleles separate during cell formation so that
recessive and dominant allleles are received by different cells.
·
Alleles have different and unique
characteristics that are unrelated to other elleles.
Using this method, scientists have identified 584 Mendelian
diseases: where one gene causes a specific disease. Most of genetic studies are
based on this methodology. But such methodology remains flowed in reasoning.
Just because a group had a specific gene, and a control did not, does not
define a causal relationship. The syllogism is wrong. Just because all As have
Bs does not mean that all Bs have As.
Such fault in reasoning in our genetic understanding of
Mendelian diseases was exposed by Rong Chen and his colleagues who performed a comprehensive
screen of 874 genes in 589,306 genomes—individuals—with 874 implicated genes.
This comprehensive study led them to identify 15,597 candidates where their
genes did not match the expression of the disease. After rigorous elimination
of candidates for various technical and theoretical reasons, a final list of 13
candidates remained. All these individuals had either both pairs of a recessive
gene, or one of a dominant gene that causes one of eight type of Mendelian disease.
These Mendelian childhood disorders would normally be expected to cause severe
disease before the age of 18 years: cystic fibrosis, Smith-Lemli-Opitz
syndrome, familial dysautonomia, epidermolysis bullosa simplex, Pfeiffer
syndrome, autoimmune polyendocrinopathy syndrome, acampomelic campomelic
dysplasia and atelosteogenesis.
There are three possible interpretations of this outcome.
That the Mendelian diseases identified were in fact incorrectly defined and
there might be other genes involved. Secondly, that these individuals are
resilient—in ways unknown--to the disease. The third possibility being that
there are other factors—including genetic factors as well as epigenetic
influence--that determine whether genes express into a disease--genotype
expresses into a phenotype.
The overarching outcome of this study is however the
importance of logic/reasoning and the scientific method. Science is nothing but
method. The results of scientific work are always incomplete since science is
not about the outcomes but about the method. In gerontology this study
contributes to a continuing appreciation of how genetics might be the road map,
but we are in fact the drivers of our journey through life.
Reference:
Chen, R., Shi, L., Hakenberg,
J., Naughton, B., Sklar, P., Zhang, J., ... & Sleiman, P. (2016). Analysis
of 589,306 genomes identifies individuals resilient to severe Mendelian
childhood diseases. Nature biotechnology.
© USA Copyrighted 2016 Mario D. Garrett
