What Is A Genetic Mutation & How Do Gene Variants Affect Health?

What Is A Genetic Mutation & How Do Gene Variants Affect Health?

From Spiderman to The Incredible Hulk, genetic mutations are a staple of comics and films, often conferring powers such as super strength or agility. In reality, mutations happen often and are mostly benign. With that being said, gene variants can sometimes increase our risk of disease and, in other cases, confer benefits. But what are genetic mutations, how do they happen, and what can we do if we are at risk for genetic disorders? Stick around to find out.


Table of contents:


DNA & the double helix

DNA, or deoxyribonucleic acid, is a molecule that contains the genetic instructions for all living organisms, including you! The DNA sequence codes for proteins, the building blocks of life, detirmining everything from your eye colour and height to your risk of certain diseases.

A DNA molecule looks like a twisted ladder and is known as the 'double helix'. It consists of two double-sided strands of alternating sugar (deoxyribose) and phosphate groups wrapped around each other. Collectively, this is known as a nucleotide. These two strands are connected by four chemical base pairs, including:

  • adenine
  • cytosine
  • guanine
  • thymine

These bases always pair together in the same way: A with T, and C with G. What's more, the order of these letters influences the content of the instructions, similiarly to how the letters of the alphabet form different words. For example, ATCGTT might instruct for blue eyes, while ATCGCT might instruct for brown.

In humans, most DNA is tightly encased in a nucleus cell, known as a chromosome. This is called nuclear DNA. As well as nuclear DNA, humans also have a small amount of mitochondrial DNA, which powers the cell. Mitochondrial DNA only comes from the maternal line.

Humans have 23 pairs of chromosomes, or 46 in total, with 2 of these being sex chromosomes. Some individuals have an extra chromosome that is responsible for genetic disorders, such as Down's syndrome.

A 3D animation showing how DNA code becomes a functional protein

A code that cannot be read is useless, so how does the information stored in DNA become a functional protein? Known as the "central dogma" of molecular biology, the process goes as follows: DNA molecules replicate themselves and produce new DNA. This DNA then makes messenger RNA (transcription), which in turn, create proteins (translation). The reality is a little more complicated, but broadly speaking, this explains the process accurately.

Amazingly, humans share around 60% of their DNA with both bananas and fruit flies! In fact, fruit flies are one of the most studied insects because they share nearly 75 per cent of the genes that cause diseases in humans.

Fun Fact?☝ Did you know: If all the DNA from a single human cell was stretched out end-to-end, it would make a six-foot-long strand!

What is a gene?

As we have touched upon, DNA sequences contain instructions on how to build proteins and other molecules. These sequences are known as genes. Only 1% of our DNA is actually made up of protein-encoding genes; the remaining DNA is known as non-coding DNA which regulates transciption and translation.

Genes can range from a few hundred base pairs to as many as 1 million, all of which contain blueprints for unique traits. We receive 50% of our mother's genes and 50% of our father's genes, making us similar but not identical to both.

Humans share many of the same genes with each other; in fact, we are over 99% similar! It might not sound like much, but this small difference accounts for the vast variations we witness in both health and appearance.

Humans possess a pair of each chromosome, ranking 46 collectively, meaning they have two versions of each gene. These versions are called alleles and can be either dominant or recessive.

Dominant alleles manifest themselves even if there is only one copy of them. For example, a dominant brown eye gene will result in brown eyes, even if you have a recessive blue eye gene as well. On the contrary, recessive genes require both alleles to be the same for the characteristic to be expressed; you would need two recessive blue eye genes for this to influence your phentotype. Pheno what? In short, a phenotype is simply an individual's observable traits.

Fun Fact?☝ Humans have around 20,000 genes, whereas a humble grain of rice has around 40,000. Collectively, your gut microbiome has over 20 million genes!

What are genetic mutations?

Genetic mutations are random changes in the DNA sequence that can be caused by environmental factors or inherited at birth. Those acquired during your life by factors such as UV light, X-rays, cigarette smoke and copying mistakes during cell division are called somatic mutations. These cannot be passed onto offspring as they occur after conception and in cells other than the sperm or egg.

A short explanantion of what genetic mutations are

The most common somatic mutations are single nucleotide polymorphisms (SNP'S), meaning a single letter is changed in the DNA code. These occur around once in every 300 bases. When copying errors occur during cell division, our DNA repairs the majority of them before the gene is expressed. With that being said, sometimes mutations can go unnoticed, leading to permanent mutations.

When letters in our DNA code are changed, it alters the instructions in that genetic code, for better or worse. Genetic mutations mostly have no effect at all; however, small changes can adversely impact health. For example, just one letter deleted or changed can result in a damaged protein, extra protein, or no protein at all, all of which have serious consequences.

Genetic mutations which are inherited at birth are known as germline mutations; an example is sickle cell anaemia. Germline refers to mutations that occur in the sperm and egg. This genetic information is the source of all DNA for every cell in the body.

Type of mutation Effect on DNA sequence
Deletion A letter is deleted from the DNA sequence.
Inversion A sequence of a chromosome is reversed end-to-end, for example, T, G, C become C,G,T.
Substitution A sequence of letters are replaced by the same amount of letters.
Duplication When letters are duplicated in the sequence, for example, T,G,C becomes T,T,G,C.

The good, the bad and the benign

Warren Umoh.
The DNA Double Helix

Genetic mutations can be beneficial, harmful or neutral; for example, some mutations can predispose an individual to cancer or Alzheimer's disease, whilst others confer lactose tolerance and HIV resistance. Some individuals even have a gene that enhances muscle endurance, making them naturally strong runners.

Mutations account for genetic variation among species. By extension, they enable evolution via natural selection, a process in which organisms that develop beneficial traits survive and prosper, whilst those with less helpful traits are selected against.

For example, a frog might develop a mutation that gives them a green skin pigment, allowing them to camouflage from predators. This helpful adaptation, though entirely random, will allow more green frogs to survive and pass on their DNA to successive generations.

The most famous emblem of this process is Charles Darwin's Galapagos finches. In short, Darwin observed that fruit-eating finches had parrot-like beaks whilst insect-eating one's had narrow, elongated beaks. These features perfectly suited their diet and habitats. As we now know, animals experience random mutations, some of which can aid survival. Over time, those who have beneficial mutations thrive and pass on these genetic variants.

Fun Fact?☝ The Finnish Skier, Eero Mäntyranta, was suspected of doping because his red blood cell count was so high. It turned out that this was a result of a mutated gene that ran in his family and was likely a factor behind his freakish endurance. He won seven Olympic medals in his lifetime.

Genetic diseases: single-gene and complex disorders

Genetic diseases are classed into two types: complex and single-gene disorders. Complex diseases are influenced by multiple factors, including lifestyle, environment and multiple genetic variants. For example, coronary heart disease has around 60 genetic variants that are associated with it, alongside lifestyle factors such as smoking and sedentary habits. These are also known as polygenic disorders.

In contrast, single-gene disorders are caused by one variant in a specific gene. Cystic fibrosis, sickle cell anaemia and a rare disorder called Tay-Sachs are all examples of this. There are around 10,000 disorders caused by a single genetic variant, and they affect around 1% of the population. These can be foreseen more easily than complex diseases as they have predictable patterns of inheritance.

Researchers are continually conducting Genome-Wide Association Studies (GWAS), which look to see which gene variants are common in those with certain diseases. This can be particularly helpful when trying to predict complex diseases.

For example, BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes that produce proteins that help repair damaged DNA. All humans have two pairs of these genes, one from their mother and one from their father. In some cases, mutations in these genes can result in harmful variants, increasing a person's risk of breast and/or ovarian cancer.

For reference, 13% of women in the general population will develop breast cancer at some point in their lives. By contrast, 55%–72% of women who inherit a harmful BRCA1 variant and 45%–69% of women who inherit a harmful BRCA2 variant will develop breast cancer by 70–80 years of age.

If you take the Atlas DNA test, you'll discover your risk level for 20 multifactorial diseases as well as your carrier status for 322 hereditary conditions. To do this, we draw on the latest GWAS research to determine whether you possess any gene variants associated with disease risk. This can inform you whether you are genetically predisposed to certain conditions, including Parkinsons, obesity and coronary heart disease.

Did you know?☝ The laws of heredity were discovered by a monk named Gregor Mendel, who experimented on pea plants.

I'm genetically predisposed to a condition, now what?

Warren Umoh.

A genetic predisposition does not mean you have a condition nor guarantee that you will develop it. Instead, this simply means that you possess a variant that is more common in those with a certain disease. Whilst this can be alarming, there are many steps you can take if you discover that you are at an increased risk for a disorder.

Firstly, we recommend that you consult your GP and get screened. In many conditions, early detection can improve health outcomes going forward. Additionally, you might want to consult a genetic counsellor. They can advise you on what steps to take going forward and explain any test results you may have received. A genetic counsellor can also guide you on the path to parenthood and help you to manage and minimise risks.

Moreover, there are many lifestyle changes you can make to manage risk factors when it comes to complex diseases. Though it depends on the condition you are at risk for, there are a few measures you can take which apply to most polygeneic diseases, including:

  • Quit smoking
  • Manage stress
  • Make sure you get sufficient sleep
  • Excercise more
  • Eat a diet rich in different coloured fruits and vegetables

Is DNA our destiny?

Whilst a small number of traits are mainly controlled by one gene, many common diseases are influenced by multiple factors as well as genetics, including your lifestyle and environment. As we touched upon, these are known as complex diseases and include type-2 diabetes, heart disease and cancer, among other conditions.

The health choices you make each day are important, including the amount of exercise you get, your diet, and whether or not you smoke. All of these factors can tip the balance against disease and influence how your genome works.

What's more, even if you have a genetic variant associated with a complex disease, you can often minimise the risks by making lifestyle changes. Ultimately, your DNA is not your destiny, as we shall explore further.

The Human Microbiome: looking beyond our own DNA

When it comes to health, our DNA is not the full story. Even beyond lifestyle and environment, there is another important factor at play. In short, humans play host to trillions of bacteria in the gut, collectively known as the microbiome.

This inner world impacts everything from metabolism to mood and is increasingly being acknowledged as central to our health. The bacterial genes in the gut microbiome outnumber our human genes by over 100 to 1 and exist symbiotically with us. This means that whilst we shape the microbiome, our microbiome can shape our health also, conferring health benefits or increasing disease risk.

There is much that we do not know about the human microbiome, but as research emerges, we are gradually learning that it plays a large part in disease risk and prevention. Though the research is nascent, imbalance in the microbiome has been associated with a wide array of conditions, including:

  • Depression & anxiety
  • Inflammatory bowel disease
  • Autism
  • Obesity
  • Type-2 Diabetes
  • Bowel cancer

On the contrary, a balanced microbial community can reduce inflammation and support the immune system. Ultimately, the microbiome is another important factor detirmining health outcomes which shows that DNA is not our fate.

Did you know?☝ In the Atlas Microbiome Test, we analyse your bacterial DNA, enabling us to tell you which bacteria you have, which you lack and how to encourage the ones you need! We also provide weekly, personalised food recommendations to help improve or maintain your gut health.

Unlike our DNA, this ecosystem is dynamic and responds to lifestyle and dietary changes. As such, we can potentially harness benefits from microbial genes by cultivating this garden within. There are a few ways to encourage diversity in the gut, including exercise, increasing your intake of prebiotic foods and eating a diet rich in plant-based fibre and colourful vegetables.

Takeaway

  • DNA molecules code for proteins, the building blocks of life
  • Genetic mutations randomly occur in the DNA code, but most are repaired before the gene is expressed.
  • Some mutations can become permanent, leading to variation in species.
  • Mutations are mostly benign but can sometimes lead to harmful gene variants or even confer benefits.
  • Researchers are constantly looking at which gene variants might be associated with specific disorders.
  • Whilst a small number of diseases are caused by a single gene variant, many disorders are polygenic, meaning that lifestyle, diet, environment and genes all play a role in their development. In some disorders, as many as 61 harmful variants have been pinpointed.
  • The bacterial genes in our gut microbiome outnumber our human genes by 100 to 1.
  • An imbalance in our microbiome is associated with many conditions.
  • We can shape our microbiome through diet and lifestyle.

☝️DISCLAIMER☝This article is for informational purposes only. It is not intended to constitute or be a substitute for professional medical advice, diagnosis, or treatment.

Ross Carver-Carter
Ross Carver-Carter Relationship counsellor for humans and their microbes

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