Question

A friend who works in a research lab has discovered a tight association between a SNP allele and the disease she is studying. She says this means the SNP allele must be the mutation that causes the disease. Explain why she is likely to be wrong.

Short answer

In conclusion, a strong association between a SNP allele and a disease does not necessarily imply causation. This is because non-causal factors such as linkage disequilibrium and coincidence could be responsible for this association. Furthermore, establishing causality requires functional characterization of the SNP to understand its biological role in the development of the disease.

Step-by-step solution

Understand SNP (Single Nucleotide Polymorphism)

SNP stands for Single Nucleotide Polymorphism, which is a variation in a single nucleotide occurring at a specific position in the genome. Such variations in the DNA sequence occur naturally and can be found throughout the genomes of different individuals. While some SNPs can lead to the development of diseases, others have little or no effect on an individual's health.

Association vs. Causation

An association between a SNP allele and a disease means that the SNP allele and the disease are observed together more frequently than expected by chance. However, an association does not imply causation. There could be other underlying causes or confounding factors that lead to such an association. A confounding variable is an external factor that affects both the independent and dependent variables, causing a false assumption about the relationship between them.

Examples of Non-causal Associations

1. Linkage disequilibrium: The SNP allele can be in close proximity to the actual causal mutation, and they inherit together, creating an association. 2. Coincidence: The SNP allele and the disease may have occurred together in the population by chance but not necessarily because the SNP allele is causing the disease.

Functional Characterization of a SNP

One way to establish causality is to examine the biological function of the SNP allele. Researchers can perform functional studies to determine whether the SNP allele has a direct effect on the protein or gene expression levels leading to the disease phenotype.

Conclusion

In conclusion, observing a strong association between a SNP allele and a disease does not necessarily mean that the SNP allele is the mutation causing the disease. Other factors could be causing the observed association, or the SNP allele might be linked to the actual causal mutation but not be the causative factor itself. Additionally, researchers would need to perform functional studies to confirm causality.

Key concepts

Single Nucleotide Polymorphism (SNP)

A Single Nucleotide Polymorphism, or SNP, is a special type of genetic variation. In simple terms, it's like a small typo occurring in a single nucleotide of a DNA sequence at a particular location in the genome.
These tiny changes in the DNA code happen naturally and are common in our DNA.
You will find them throughout the entire genome in different people. Not all SNPs influence health. Some SNPs may play a role in disease development, while others might have little impact on an individual's well-being.
Researchers pay close attention to SNPs because they can give clues about disease risk and drug responses. However, it’s important not to jump to conclusions about their effects without further studies.

Linkage Disequilibrium

Linkage disequilibrium is a term used to describe a situation where certain combinations of genetic markers appear together more often than would be expected by chance alone.
It happens when SNPs (or other genetic variations) are inherited together because they are very close to each other on a chromosome. Imagine two cars traveling together on a road. If they're connected via a tow bar, one is likely to follow wherever the other goes; this is similar to how genes linked by linkage disequilibrium behave.
Although some SNPs show an association with diseases, they might be "traveling" with another, actual causal mutation due to linkage disequilibrium.
This means the SNP itself may not be responsible for the disease, even if it seems closely related.

Functional Studies

Functional studies are a key part of understanding whether a SNP actually affects a disease or not.
These studies investigate the biological role of a specific SNP in detail, asking questions like: "Does this SNP change how a gene is expressed?" or "Does it alter the function of a protein?" To carry out functional studies, scientists will often:

• Examine the gene or protein linked to the SNP to see if its function is modified.
• Manipulate the SNP in cell or animal models to observe any changes in biological outcomes.
• Utilize techniques like CRISPR to edit the genetic code and pinpoint the SNP's effects.

These approaches can help confirm whether a SNP is simply associated with a disease or if it directly causes it.

Causation vs. Correlation

When we talk about causation and correlation, we're diving into how two things can be related. Correlation is when two events occur together but don't necessarily impact each other.
Causation, on the other hand, means that one event is the result of the other occurring. Imagine you notice that ice cream sales and drowning incidents both rise in the summer. They’re correlated – they happen at the same time – but eating ice cream doesn't cause drowning. Warm weather causes more people to swim and eat ice cream.
Similarly, a strong correlation between a SNP and a disease doesn't always mean the SNP causes the disease.
Researchers must dig deeper to explore other factors and avoid jumping to conclusions about such relationships.