Episode 3 - Genetics

Before we get into food let's get into how our body responds to food.

Our body is like a loaf of bread and our genetics are like the recipe that tells our cells (the chef) what to do. I use this silly analogy because our cells use food as energy and building blocks but they only know how to do that because of our genetics (the recipe book). We all look different and have unique personalities and responses to our environment (and our food) because of just a few genes.

There have been many studies published in peer reviewed journals looking at the effects of our genetics on our responses to food. Questions such as why do some people gain weight and others loose weight on the same diet? have been studied for decades. Below are some great publications that really get into those questions.

• Genetics and Obesity – The Lancet

• Gut-brain cross talk in metabolic control – CELL

• The genetics of adiposy – Genetics and Development

So if it is all about DNA, why don't we have DNA tests to tell me what to eat?

This is a great question, and I think we will have better genetic tests in the future as the human genome project continues to produce incredible new insights. Genetic testing requires many clinical trials and laboratory analysis because genetic expression is complicated and intertwined. When you are born a series of genetic tests are run to identify inborn errors of metabolism, meaning genetic causes of diseases some of which will change the patients diet for life. I am not going to get into all the inborn errors of metabolism on this podcast but I have linked resources for you here to learn more about them. I bring it up because physicans use genetic testing all the time to diagnose diseases, but as of Jan 2020 we do not yet have genetic testing to give you an exact life book for your health. I want to get into the details of our genetics so that you understand what our DNA is and how it affects us so that you have a good foundation to read more about this subject and you have a good starter to understanding genetic testing if you were ever to get tested.

So I want to get into what is DNA?

DNA is the genotype (the genes) and the expression of that DNA is the phenotype (what you see, for example brown hair is a phenotype). However, just because we have the genetic code for something doesn’t mean it will be expressed, some genes have a higher risk of being expressed such as dominant genes. You might remember learning about Mendelian genetics in high school. Mendel demonstrated that we can have dominant and recessive alleles. Alleles are variant forms of a given gene. For example you have an allele for the color of your hair, and hair-color is the gene. In the most simple explanation, dominant alleles are expressed on their own and recessive alleles are expressed when they are inherited as a pair. When you inherit the same allele from each parent, you have inherited the pair and we call his homozygous meaning the same allele was paired. When you inherit a different allele from each parent we call this heterozygous. A dominant allele can be expressed in a heterozygous pair and a recessive allele is usually only expressed when inherited in a homozygous pair. If you have the allele for something you have the ability to pass it onto your children even if you do not express that allele. There are many diseases that are caused by recessive genes, meaning both parents carried the recessive gene and did not express it but happened to both pass it to their child who now has the disease. This is why we do prenatal genetic trees and testing.

Having a gene doesn't always mean expression. This is where genetics gets complicated and this added layer of gene regulation is what we call multifactorial expression. Meaning some genes have many factors that regulate their expression. Multifactoral genetic expression is the most relevant to the small differences in each of us that determine whether we will get type 2 diabetes or high cholesterol. So to understand this we have to go back to the basics of cell biology, a journey to the nucleus of the cell. Gene expression is regulated by proteins within the nucleus of the cell. The nucleus is the house inside the cell where DNA lives, there are doors to this house (nucleus) where proteins can enter and exit but DNA doesn't leave the nucleus in a healthy cell. DNA regulation occurs through modifying the proteins that wrap up DNA, these are called histones. These histones are modified by adding things to them this is called methylation or acetylation. When you inherit how your parents had regulated their genes you are inheriting how their genes were methylated or acetylated and this is called epigenetics or imprinting, this is how you can express the same genes your parents or grandparents expressed. If a gene is methylated it is repressed, meaning that the gene will not be expressed. If a gene is acetylated it is expressed being you will be able to see it (brown hair). Unfortunately we do get DNA regulation information from DNA tests. So you might have the gene for something but you might never express that gene, meaning it is not enough to know whether or not you have the gene, you have to know if that gene will be expressed. DNA tests that your physican runs are based on the genetic inheritance of the gene and what we know about how the gene is expressed. When a gene has multifactorial expression instead of basic mandellian expression the DNA test is used in conjunction with tests that look at the expression of those genes. DNA testing that your doctor runs is complicated and requires that your doctor complete a special residency and fellowship.

The expression of DNA. For a gene to be expressed it must be transcribed into a protein. And there are proteins that can block the transcription. Transcription in it's most simple form is going from DNA-->mRNA-->proteins. The proteins created can be proteins that build the cell or that regulate DNA or transcribe DNA to make more proteins. To fully know if a genotype is going to turn into a phenotype we have to know if the protein for which it codes is being produced. The proteins created from DNA become the workers of our body, they are the enzymes that build cells and break down our food. Proteins created from our DNA direct the function of our cells.

Our environment (what we eat etc) also affects how proteins are expressed and how they interact with our DNA. So to answer the big 'WHY' behind why we all have different responses to food I just want to say it is complicated. Because most of our genes are the same we can generalize our guidelines and help most people. But because of multifactorial genetic inheritance and how our environment affects our genes you might find that you do better on a specific diet or training plan or meal frequency that is different than the guidelines. This doesn't mean that the data that supports those guidelines is wrong or that the guidelines are bad, it just means that you have unique genetics that are not captured by that research or those guidelines. For anyone who has a chronic disease/health condition (diabetes, cystic fibrosis, high blood pressure) I recommend you talk with your doctor or registered dietician about what changes would benefit you specifically. There are guidelines specific to each chronic disease/health condition and I will be getting into some of them at the end of this series as well.

So to summarize this fun throwback to high school biology I want you to have learned:

• The genetics that make us different from each other is a small fraction of all the genes we carry

• These genes determine our features like our hair color but also determine how we respond to our environment. Some of these genes are affected by our environment (multifactorial) and this can cause us to have some unique individual dietary needs

• This is one of the reasons it is so difficult to run nutrition research. You are comparing a complicated system (your body) to another complicated system (a whole diet made of up lots of foods). And despite that complication we still have some really great publications and data from nutrition research that informs our guidelines.

• Keep this episode in mind when you hear about a new nutrition study and why it worked in the population studied.