Sunday, November 2, 2014

Who Are You?

On a societal level, that’s a relatively easy question to answer. You’re either living as a man or a woman, are somewhere between young and old, probably play a role in a family structure as a parent, child and/or sibling, developed or learned some type of skill, and have some form of social interaction with others.

However, on a biological level, there's a much more complicated answer.

Here’s what scientists know. You are part of the group known as Homo sapiens (although some of you contain Neanderthal genes-some 20% of Neanderthal genes are still prevalent among some of us although no one has more than 1%), you have about three billion gene pairs, and you resemble other humans in terms of types of genes as closely as 99.9%. But, and it's a big but, it’s the last .01% that makes you possibly very different from others, including family members. (Even identical twins do not match up 100% gene-wise.) These genetic variants, as scientists often refer to these differences, can determine many things that uniquely happen to you.

Although I’ll leave it up to the reader to learn more about genes in general on your own, I will point out that there are two major creators of genetic variants. Certain variants come from germline genes, the genes you are born with, and others from somatic mutations, the genes that can develop over the course of your life. It is now estimated that there are probably hundreds of millions of such variants and the combinations of such variants is a really big number, creating all kinds of scenarios.

Over the past few weeks, the significance of these variants were highlighted to me through several studies. For example, a recent study showed that some type two diabetics with a certain variant did not benefit from exercise, a finding that really flies in the face of intuition. Another study showed that people who get a brain hemorrhage from taking blood thinners are more likely to have a certain gene variant.  It may be prudent to hold their bloodthinner and weigh the benefit/risk more carefully. A third study revealed that aspirin prevents colon cancer in certain people with a particular gene variant. In others, like me, it cause ulcers.

The most poignant example of the role of gene variants was the discovery that certain super-centenarians, people over the age of 110, possess a group of small variants that collectively appear to protect them from or delay the onset of certain common ailments such as cancer and heart disease, despite these old old being obese, smoking their entire lives, and being sedentary.  In other words, they did everything wrong from a lifestyle perspective and still outlived everyone.

Ever since the Human Genome Project, a project whose goal was determining the sequence of chemical base pairs which make up human DNA, and identifying and mapping all of the genes of the human genome from both a physical and functional standpoint, was declared completed in 2003 (although not all genes were actually identified and the genome was comprised from multiple people), scientists have been seeking to identify all the possible gene variants and most importantly, map them to human health and disease.

These efforts extend to several research fields, most notable (in my opinion in terms of most immediate impact) among them today being pharmacogenetics and epigenetics. Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. This means that doctors can adjust your medications and related dosages based on knowing whether or not you will respond positively based on your genetic profile. For example, tens of millions of Americans take statins, yet only one out of a hundred get a real benefit from them. Imagine if researchers could identify who that one is and spare the other ninety-nine from taking a medication unnecessarily, thereby sparing their money and avoiding side effects.

Epigenetics is a more complicated as it is research that tries to determine how environmental factors influence inherited genes. For example, epigenetics could identify those people at significantly increased risk of developing cancer from consuming alcohol and eliminate the guessing game for everyone else.

There are many companies springing up around the field of genetics, including companies focused on biological diagnostics and therapeutics. The trick is to identify genes that correlate to diseases and then create an intervention to change them. These research companies range from giants like Google to small start-ups like Tute Genomics, with many new players constantly emerging.

With hundreds of millions now being spent on connecting the dots between which genes promote health and which lead to disease, I am extremely optimistic that there will be some major breakthroughs within the next twenty years.  With these discoveries, you will be able to much better answer the question of who you are, at least from a genetic perspective. Until then, don’t be surprised that what works for one person doesn’t work for another.  It’s may simply be an unidentified genetic variant at play.

4 comments:

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