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The human genome
DNA is the language of life.
Your DNA is made of a long, unique sequence of about 6 billion chemical bases represented by the letters A, C, G, and T. The entirety of one's DNA, every one of these billions of letters, is referred to as the "genome".
All organisms, including humans, fruit flies, cows, and fish, begin from DNA.
If all animals start off as DNA, though, how are we all unique? It’s because not every species has the exact same sequence of DNA letters in their genomes. For example, human beings and dogs share 94% of their DNA. It’s that 6% that makes all the difference (1).
How about among humans? Although your genome is essentially the same as every other person, there's an average of about 30 million DNA letters that differ between people. This means the genomes of two individuals typically differ by around 0.5% (2).
These 30 million letters, called variants, help explain your uniqueness, including your disease and trait dispositions — from specific cancer risks to the severity of allergies.
Nucleus' core mission is to see how the variants in the genome help shape who people and their future children are so they can live a healthier and more informed life. Let's dive in.
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What are variants, and how do they work?
The first thing to note is that variants aren’t all created equal — they each have a different magnitude of effect. We can divide variants into two general categories: high-effect and common.
Variant type #1: High-Effect variants
If you have a high-effect variant, you have the disease or trait.
Some variants have a strong effect on their own. These variants are entirely responsible for whether a person develops a disease or trait. Often termed "pathogenic variant," this usually refers to a DNA difference that can single-handedly cause a feature.
Let’s look at our friends, Karl and Maya, to illustrate how variants work.
One day, while strolling in the park, a radioactive spider suddenly jumped off a tree and bit Karl and Maya. Neither of them turned into a superhero (unfortunately, it wasn't that kind of spider), but they did develop some DNA variants.
The variant in Karl's DNA unfortunately caused him to develop a disorder called congenital sucrase-isomaltase deficiency (CSID). Karl can't eat fruit again without risking severe stomach pain and other issues.
If he wasn't a cartoon character, Karl would likely have inherited this causal variant for CSID from his parents. Other monogenic diseases like CSID include cystic fibrosis, Tay-Sachs disease, and sickle-cell anemia.
Here's the thing: high-effect variants, while powerful in impact, are pretty rare. They don’t cause many of the diseases you’ve probably heard of.
Most DNA variants, unlike high-effect variants, influence but don't guarantee the development of diseases and traits. These are called common variants.
Variant type #2: Common variants
Unlike Karl, our friend Maya didn't develop one high-effect variant. Instead, she developed multiple common variants.
These variants have small effects on your diseases and traits, and tend to be more common compared to high-effect variants.
One of these variants won't significantly affect your disposition toward a disease or trait. But several of them working in combination can have a meaningful impact.You have to consider common variants jointly, seeing how they, alongside any high-effect variants, collectively dispose you towards a feature.
So, Karl developed a single variant causing him to get CSID. Maya's variants, however, work collectively to affect multiple aspects of her health and personality, whether predisposing her to diseases like type 2 diabetes, or influencing characteristics like her muscle strength or her inclination to take risks.
In reality, people don’t just have a high-effect variant or common variants. They can have a mix of the two.
From monogenic to polygenic features
Here’s the moral of the fable of Karl, Maya, and the spider: Most DNA variants work together to shape your characteristics. It’s usually not a single variant that causes a feature.
Familiar diseases and traits like cancers, heart disease, height, or extraversion are products of many of these common variants, or a mix of high-effect and common variants collectively influencing your risks and traits. These sorts of features are called "polygenic."
But when it comes to polygenic features, genetics isn’t destiny — your lifestyle, family history, clinical factors, and environment are also important variables to consider.
You might now be curious to discover what variants in your DNA might affect you or your future children.
Well, now you can find out with a Nucleus DNA test.
References
1
Ostrander EA, Wayne RK. 🔗 The canine genome. Genome Res. 2005 Dec;15(12):1706-16. doi: 10.1101/gr.3736605. PMID: 16339369.
2
Levy S, Sutton G, Ng PC, et al. 🔗 “The diploid genome sequence of an individual human.” PLoS Biol. 2007 Sep 4;5(10):e254. doi: 10.1371/journal.pbio.0050254. PMID: 17803354.
3
Ségurel L, Bon C. 🔗 On the evolution of lactase persistence in humans. Annu Rev Genomics Hum Genet. 2017 Aug 31;18:297-319. doi: 10.1146/annurev-genom-091416-035340. Epub 2017 Apr 19. PMID: 28426286.
4
Clancy, S. (2008) 🔗 Genetic mutation. Nature Education 1(1):187
5
🔗 “What kind of gene variants are possible?” MedlinePlus.
6
🔗 "The sound of a silent mutation” Science.
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