What is Linkage Disequilibrium?

Imagine genes as passengers on a train. Sometimes, passengers who sit close together tend to get off at the same stop. Similarly, genes located near each other on a chromosome tend to be inherited together. This phenomenon is called linkage.

Linkage disequilibrium (LD) refers to a situation where certain combinations of gene variants (called alleles) occur more or less frequently than expected by chance. It’s like noticing that passengers with red hats and blue coats always get off at the same stop together, even though there’s no obvious reason why.

Genes and Their Locations: Alleles and Loci

Before we go further, let’s define a couple of terms:

• Alleles: Different versions of a gene. Think of them as different flavors of ice cream – chocolate, vanilla, strawberry, etc.
• Locus (plural: Loci): The specific location of a gene on a chromosome. Think of it as the address of the ice cream shop.

Why Do Genes Travel Together?

Genes located close to each other on the same chromosome tend to be inherited together because chromosomes are passed down as whole units. During the formation of sperm and egg cells, chromosomes can exchange segments of DNA in a process called recombination. However, genes that are very close together are less likely to be separated by recombination.

Recombination: Shuffling the Deck

Recombination is like shuffling a deck of cards. It mixes up the genes, creating new combinations. The further apart two genes are on a chromosome, the more likely they are to be separated during recombination.

Linkage Equilibrium vs. Disequilibrium

• Linkage Equilibrium: When the combination of alleles at different loci occurs at the frequency predicted by chance. It’s like seeing passengers with red hats and blue coats getting off at different stops randomly.
• Linkage Disequilibrium: When certain combinations of alleles occur more or less frequently than expected. This is like the red-hatted, blue-coated passengers always getting off together.

What Causes Linkage Disequilibrium?

Several factors can cause LD:

• Genetic Drift: Random fluctuations in allele frequencies, especially in small populations.
• Population Bottlenecks: A drastic reduction in population size, which can change allele frequencies and increase LD.
• Founder Effects: When a new population is established by a small group of individuals, their allele frequencies may not represent the original population, leading to LD.
• Natural Selection: If certain allele combinations provide a survival advantage, they will become more common, creating LD.
• Mutation: New mutations can be in LD with nearby alleles.

Why Does Linkage Disequilibrium Decrease Over Time?

Recombination gradually breaks down LD. Over many generations, the non-random associations between alleles decrease.

Why is Linkage Disequilibrium Important?

LD is a powerful tool in genetic research:

• Genome-Wide Association Studies (GWAS): LD helps scientists identify genes associated with diseases. By looking for alleles that are in LD with a disease, researchers can pinpoint the location of the disease-causing gene.
• Understanding Population History: LD can reveal information about the history and evolution of populations.
• Predicting Genotype-Phenotype Correlations: LD can help predict the relationship between genes and observable traits.

Measuring Linkage Disequilibrium

Scientists use various statistical measures to quantify LD, such as D’ and r². These measures indicate the strength of the association between alleles.

Conclusion

Linkage disequilibrium is a fundamental concept in population genetics. It helps us understand how genes are inherited and how they contribute to complex traits and diseases. By studying LD, researchers can gain valuable insights into the genetic basis of human health and disease.