YOUR GENES | part 1
You might be wondering, what's the connection between our genes and nutrition? A fair question, indeed.
Our understanding of genes and DNA often stops at the fact that they're inherited traits from our parents, that make up who we are.
For the most part, that’s about as far as I thought about it too until about 15 years ago, when I was hit with the realisation that my genes could have a profound effect on my health - and that certain genetic variants could significantly alter my wellbeing.
At that time, I was wrestling with some serious health challenges. During a lengthy period of illness, fatigue, and inflammation, I sought medical help and had some blood tests done.
The results revealed abnormally large red blood cells and very high levels of homocysteine, a substance typically found in low concentrations in our blood.
The doctor, a bit of a maverick for his time, decided to also test for any genetic variants in the MTHFR gene, (in addition to my levels of homocysteine, active B12 and red cell Folate). The test results showed that I had a specific genetic variant in the MTHFR gene, which made it very challenging for my body to metabolize folate from my diet, and even more so to metabolize synthetic folic acid.
This issue was causing my red blood cells to form abnormally and become less able to carry oxygen, whilst the excessive homocysteine in my bloodstream was aggravating my inflammation and was associated with the other health issues I was facing at the time (too many to mention here).
If left unchecked, it could increase my risk of developing heart disease, stroke and cancer (all of which, unfortunately, commonly ran in the family).
As it turned out, later that year after a string of unsuccessful investigations into my gastrointestinal issues, I saw a gastroenterologist, underwent a colonoscopy and had a highly premalignant polyp excised. But, even then, symptomatic relief was limited.
It was not until I started to meet the very specific nutrient requirements my body needed to counter this gene variant that I started to notice a significant, lasting improvement in my health.
Thus began my expedition into the world of genes, starting with MTHFR - one of the most notable genetic variants with research going back to the mid '90s.
My health scare happened in 2010, which was 15 years into the research on MTHFR, and less than 10 years into broader research of the human genome. Suffice to say, the body of knowledge has increased exponentially since then.
I do owe it to that doctor. Little did he know he sparked my ongoing fascination with the relationship between nutrition, genes, and human health. This led me to earn a Bachelor’s Degree in Nutritional & Dietetic Medicine in 2022, all the while continuing to delve deeper into the realms of Nutrigenomics, Nutrigenetics, and Epigenetics.
There is still so much yet to know, and the learning never ceases, but I hope to share what I've gathered so far. In essence, there's a dynamic relationship between your genes, your body, and your environment.
Before we begin, I won’t be describing MTHFR much further here, as that really deserves it’s own separate article, which I am working on. But, let’s dive in further and begin by shedding some light on your genome.
WHAT IS YOUR GENOME?
Your genetic script, or the genome as it's properly called, is an ancestral gift, passed down through generations, a tapestry woven from genes and their DNA sequences. This is your genotype, a molecular blueprint that designs the unique masterpiece that is you.
Most of your genome is located within the nucleus (brain) of every cell in your body. That is of course, except for our simpler red blood cells.. “their heads they'd be a scratchin', while their thoughts are busy hatchin', if they only had a brain.”
So, unsurprisingly, this genome residing in the “brains” of cells (not to be confused with brain cells) is classified as the nuclear genome.
Your nuclear genome accounts for over 99.99% of your genetic information, and is inherited from both of your parents, composed of tightly packed linear bundles of DNA and histone proteins within chromosomes.
As you can see from the diagram above, the nucleus of a human cell cradles its chromosomes. Looking closer, these chromosomes are made up of tightly coiled chromatin; DNA elegantly wrapped around histone proteins, containing a genetic code of over 3 billion base pairs of nucleotides.
To give you a sense of scale, if you stretched out the DNA from a single minuscule human cell, it would reach about 2 meters in length!
Now, imagine if you could unfurl the DNA from every cell in your body. You would have enough to loop around the entire solar system twice, or make 1500 round trips between Earth and the moon.
Anyhow, returning to chromosomes...
We each possess a pair of each chromosome. One from your father, and one from your mother. Consequently, you have duplicates of every nuclear gene, with each duplicate referred to as an allele.
For your mnemonic pleasure, remember this: a duo of chromosomes, one sourced from each parent, resulting in a twofold set of genes within each chromosome.
And, a staggering 99.99% of these genes are mirror images of each other.
A tiny portion of your genome resides in another organelle within your cells - the mitochondria, often hailed as the “powerhouses of the cell”. This tiny portion of the genome is known as the extranuclear genome, or the mitochondrial genome.
This genome is a maternal inheritance, accounting for the residual approximated 0.0005% of your genetic blueprint. It's responsible for a handful of genes chiefly engaged in the production of ATP (adenosine triphosphate, the spark plug of cellular energy).
so WHAT EXACTLY IS DNA, and what is a gene?
DNA, or deoxyribonucleic acid, is a an intricate dance of two nucleotide strands. Each strand parades a backbone of a sugar molecule named deoxyribose, coupled with a phosphate group, and a nitrogenous base of either adenine (A), cytosine (C), guanine (G), or thymine (T).
The connection between these two parallel strands is akin to a ballet performance as the chemical bonds formed between the bases hold them in a dancer’s embrace. Picture an adenine (A) base pairing up with a thymine (T), and a cytosine (C) base twirling around with a guanine (G). This pas de deux results in the iconic double helix structure.
The choreography does not end there. Like dancers around may poles, the double helix is further wrapped into a DNA-histone complex known as chromatin, and condensed to form a chromosome.
Within DNA, sequences of paired nucleotide dancers take the spotlight. These strategically sequenced pairings of dancers provide a script for the creation of a specific protein or functional molecule in the body. This is the moment when a simple segment of paired bases transforms into a star of the show, a gene.
WHAT IS A GENE VARIANT?
Dancing on the genetic stage are two types of genomic variations: the single nucleotide polymorphism (SNP) and the structural variant (SV). The former, often known as a “snip,” is a change in a single base pair within a gene sequence, while the latter affects a larger ensemble of the genome.
The classification polymorphism (rather than variant) simply refers to a level of incidence that your variant happens to also occur within a population. If the nucleotide variation occurs >1% within a given population the variant is termed as a polymorphism. Now, let's delve into the various types of SNPs:
A heterozygous SNP is when one of the two copies (alleles) of a gene has a variation of a single nucleotide base pairing, at a specific location along the DNA sequence.
In summary; a variant only in one allele in one copy of the gene (“hetero” - different), which has been inherited from one parent.
A homozygous SNP is when both of the two copies (alleles) of the same gene has a variation of a single nucleotide base pairing, at the same location along the sequence of that gene.
Again, in summary; it is the same variant in the same two alleles within both copies of the gene (“homo” - the same) , each identical variant has been inherited from each parent.
A compound heterozygous SNP IS ALSO WHEN TWO COPIES (ALLELES) OF THE SAME GENE HAS A single nucleotide variant, however, each OF THE TWO copIES (alleleS) of the variant CAUSES A VARIATION OF A SINGLE NUCLEOTIDE BASE PAIRING AT TWO different locationS along the DNA sequence of the gene.
That last one seems a bit of a brain twister, but again, in summary; there are two variants, but unlike a homozygous variant - where the two copies (alleles) have the exact same variant at the exact same location - in this instance; one allele causes a variant in one location, and the other causes a variant in another location within the gene.
These SNPs can choreograph a range of outcomes - they may enhance or impair the gene's performance, modify the routine, or perhaps make no noticeable difference at all.
Allow me to provide further illumination. Consider the entirety of your genetic makeup, a concept we term as your genotype. Your distinctive characteristics, or your phenotype, are birthed from both your inherited genotype and the intriguing influence of epigenetics (we delve deeper into this in part 2).
To elaborate, the majority of your traits are not the brainchildren of a single gene, but rather a harmonious collaboration of several genes, resulting in what we call polygenic traits. This holds true for SNPs as well.
However, the plot thickens when we stumble upon a lone gene that holds sway over multiple traits. This intriguing phenomenon goes by the name of pleiotropic effect, with pleiotropy meaning "more ways". Fascinating, isn't it?
WHAT AREAS OF GENETICS DOES A CLINICAL NUTRITIONIST ASSESS?
It is important to note that a Clinical Nutritionist does not cross the boundaries into the realm of genetic disorders and disease risks; such matters are the purview of Clinical Genetics.
These genetic intricacies ought to be left in the capable hands of a Genetic Counsellor, who, armed with specialized training, can guide the appropriate testing and interpreting the results thereof.
Although the role of a Clinical Nutritionist does not encompass diagnosing or curing diseases, we play a pivotal part in the broader healing process, working in harmony with other healthcare professionals to optimize health.
Our expertise can also be utilized to lay the groundwork for mitigating modifiable disease risk factors, thereby aiding in disease prevention.
It is well understood that changes in our nutrition, environment, and lifestyle can have impacts on how our bodies function and impact the state of our health.
Taking into account our unique genetic makeup, we each inherit certain strengths and susceptibilities that are further influenced by epigenetics, aging, and modifiable disease risk factors including undernutrition or overnutrition, lifestyle, stress, and environmental factors.
So, that being said, Single Nucleotide Polymorphisms (and polygenic variants) that may influence nutrient absorption and metabolism, that may increase disease risk factors, and that can be optimized by fine-tuning specific nutrient intakes and environmental factors, do fall within the purview of a Clinical Nutritionist, provided they are treatable with Nutritional and Lifestyle Medicine.
This is because this kind of testing and treatment squarely resides within the realms of Nutrigenetics and Nutrigenomics.
WHAT IS NUTRIGENETICS AND NUTRIGENOMICS?
Nutrigenomics is defined as the analysis of nutrients in relation to their impact on gene expression and human health. It includes research into how the bioactive components of a particular diet can upregulate or downregulate the activity of a particular gene to optimize health outcomes and reduce the risk of disease. Think of it like a meticulous exploration of how the nutrients we consume can fiddle with the dials of our genes—turning them up, turning them down— changing the resulting signal.
Nutrigenetics is defined as the analysis of genetic variations in humans (such as SNPs) and the resulting clinical response to specific nutrients. Theoretically, nutrient intakes can be fine-tuned according to an individual's genome to optimize their health outcomes and reduce disease risk. You can think of it more like a skilled tailor, finely adjusting the shape of our nutrient intakes to the unique fit of our genes, optimizing our health and slashing the risk of disease.
But how exactly do these nutrients tinker with our gene expression? And how can a genetic variant influence the absorption and metabolism of nutrients, and consequently affect our health?
Find out more in part 2.
REFERENCES:
PMID: 27894098 ; DOI: 10.1016/B978-0-12-804572-5.00001-X ; DOI: 10.1016/B978-0-12-804572-5.00002-1 ; www.genome.gov, www.genetics.edu.au/SitePages/Sickle-cell-disease.aspx ; and www.biorender.com.
