genotype-haplotype-phenotype

In the world of methylation and genetic testing things can become complicated very quickly.  I speak to patients on a daily basis who are more confused after they did their genetic test than they were before.  What we are seeing are thousands of patients testing their genetics to find the answers to their health challenge, only be left more confused, or even scared, than when they started.  It doesn’t have to be this way.

BeyondMTHFR is a project designed specifically to address this problem.  BeyondMTHFR is built to explain the hard science in meaningful terms so that more people can benefit from this amazing area of research.  That in a nutshell is why I post videos, blogs, and provide commentary on important methylation issues.  If we can’t explain the science in language people will understand, then how are going to improve healthcare?  If we can’t communicate these ideas clearly, then fewer people are going to benefit from this work.  And its with that idea in mind that I present this blog post.

In order to understand methylation you need to know three key terms – genotype, haplotype, phenotype.  As I have explained before, your genotype is what you are born with and your phenotype is how your genes turn on throughout your life.  But today I’m going to introduce the idea of haplotype and go into a little more detail about these three key concepts.

 

Genotype

Your genotype includes your unique, individual DNA.  It includes all your SNPs and all the genes you inherited from your parents.  This information is found on your variant report.  In other words, your genotype is what you get after doing your 23andme test and running your raw data through MTHFRsupport.com or LiveWellO.

The genotype is nothing more than a categorical list of individual genes.  The colorful variant reports you can download simply list whether your or not you inherited the good, bad or ugly version of a given gene.  Looking only at the genotype, while ignoring the haplotype and phenotype, is not a useful approach to treatment.  Simply looking at a list of genes in isolation, takes them out of context.

The bottom line with genotype is its impossible to effectively prescribe vitamins with only the this information.  Doing so will result in frustration, added expense, and lack of results that wastes time and energy.  To successfully treat methylation issues with nutrition you must also look at the haplotype and the phenotype before deciding on what path to go down.

 

Haplotype

Your haplotype represents your individual combination of SNPs and genes.  Other people will have the exact same haplotype as you do, but no one (except an identical twin) will have your genotype.  For example, many people have MTHFR C677T, COMT, and MAO-A.  I see this pattern all the time.  Therefore everyone with this combination is said to share the same haplotype for those genes. I would call that the high adrenalin, high anxiety, low methylation haplotype…but that is just my way of describing that group of genes.

Another example of a haplotype might be someone with GAD1, ACE, AGT, ADD1, COMT, MAO, and MTHFR A1298C.  This haplotype I would call the high stress, neuroinflammation, low gut function, w/ slow methylation haplotype.  Again, the point here is not looking at one gene, but looking at multiple genes at once.

ACE, AGT, and ADD1 influence levels of angiotensin, which is a stress hormone made by our kidneys.  When these SNPs are present the body has elevated levels of angiotensin, and this reduces blood flow to the GI tract.  Some studies show these SNPs may even cause damage to the heart valve, since increases in blood pressure and cortisol usually accompany the increase in angiotensin.

GAD1 involves the breakdown of glutamate into GABA, so the more GAD SNPs are present the less efficient the body is at making GABA.  This can lead to neuroinflammation since too much glutamate in the brain (think MSG) leads to excess brain activity, seizures, and inflammation.  With GAD1 the tendency is towards glutamate and away from GABA, and often leads to neurological symptoms that change behavior, mood, appetite, etc.

In addition to the above, when you also have the COMT and MAO SNPs the individual will struggle to break down stress hormones like adrenalin and norepinephrine.  Individuals with COMT and MAO SNPs are usually highly intelligent, driven, and susceptible to burn-out and OCD issues. Combine all of the above genes into a functional haplotype – ACE, AGT, ADD1, GAD, COMT, MAO, MTHFR A1298C – and you start to realize that each gene is influenced by other genes.

If you are treating a methylation problem and all you do is look at the genotype, but ignore the haplotype, you are going to have less than satisfactory results.  Yet even looking at both the genotype and the haplotype will leave you falling short.  To really see the big picture, to really take good care of the body and treat methylation issues, you have to study the genotype, appreciate the haplotype, and make sure you understand the phenotype!

 

Phenotype

The phenotype is the most important part of the methylation puzzle.  The phenotype concerns the named “disease” that medicine uses to label patients – obesity, cancer, metabolic syndrome, diabetes, etc.  But there is more to the idea of phenotype than just words which describe a set of symptoms.  What these words, or diagnoses, are actually describing is a process of how our genes we inherited are expressed through diet, stress, toxins and other life experiences.  The phenotype is such a big idea because it brings together the concept of genetics with what people actually experience in their day to day lives.

The phenotype is found by performing a thorough exam, history and chief complaint.  Meaning, the phenotype includes the symptoms of what the patient is complaining about and the background to how it started.  The reason why this information is important is that the phenotype is the end result of the genes interacting with the environment. When we try to treat methylation disorders we must realize that the phenotype is the biggest problem – its the only reason why a patient actually feels sick or has symptoms in the first place.  Its the reason we go to the ER or to the doctors office.  The phenotype is what we consiously experience as inside our bodies – what we would call our level of health.

For example, you cannot consciously feel your MTHFR gene.  But you can feel depressed from the expression of the MTHFR gene and depression is a well-known phenotype.  Similarly you can’t feel your COMT, ACE or BHMT genes, but you can have gallstones and chronic acid reflux which are also common phenotypes in our society.  Having depression, gallstones and/or acid reflux are not genetic problems, they are a phenotype CAUSED by the interaction of your genes and the environment within your body and your digestive system.  Allow me to say it another way:

The phenotype is the physiologic expression of haplotypes over time; the epigenetic final result of environment + haplotype (SNP combinations) yielding a particular set of symptoms such as high blood pressure, leaky gut, GB disease, panic/anxiety disorder, etc.

In other words the phenotype represents all of your SNPs plus all of the environmental influences – stress, toxins, malnutrition, etc. – combining together.  When you add everything up trying to solve the methylation puzzle, its absolutely necessary to pay attention to the phenotype.  Trying to treat methylation issues without recognizing the phenotype will lead to lackluster results.  The phenotype helps you with the most difficult question – it shows you where you need to start.

 

Conclusion

In the end treating methylation problems isn’t about following a predetermined formula.  Far from it.  Treating patients for methylation issues involves understanding where the patient’s physiology is most imbalanced and stressed.  The information that is necessary to successfully figure that out requires looking at the genotype, the haplotype and the phenotype together.

Doctors have been helping patients heal for thousands of years before we had genetic testing.  Your genes are not your destiny, but they are your tendency.  Because the world today is more toxic and more stressful than ever, it is placing added stress into our genetics and this where most methylation problems are coming from.  To prove the point of how amazing our genes are I will share one final thought:

The human genome has roughly 22,000 protein-encoding genes. Each gene can turn on or off. The question is if you have 22,000 genes, and each on can either be “off” or “on”, how many different possibilities exist inside our genes? How many different genetic combinations are possible inside our cells? Well, the answer will amaze you. The number of possible genetic expression we can have is the number 2 to the 22,000th power. That is a number so large that our brain can’t even understand it. 2 to the 22,000th power. Try and calculate that! So its just mathematic proof that we are in fact “infinite” in our ability to adapt and learn and grow and survive. Whatever genes you are born with…they are NOT your destiny!

Yours in Health,

Dr. Rostenberg

By studying the current peer-reviewed research, Dr. Rostenberg has discovered powerful, natural strategies to restore your gut and heal your body.  He can help you uncover the genetic or root causes of your health problem and find a natural solution!  If you would like help with your methylation genetics to improve your gut function and reduce/eliminate your symptoms, please contact Dr. Rostenberg at Red Mountain Natural Medicine today. Phone 208-322-7755. Email redmountainclinic@gmail.com. Website http://www.redmountainclinic.com

1 Comments

  • August 31, 2016 Reply

    Jill Castillo

    WOW !!! Just blown away !!! Of course I do not totally understand everything you said but I get the point. My wife is filling out all the paperwork to see you. She is very sick. Now I know you can look passed all the outside issues and go for the “gene” solution.

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