Linkage disequilibrium mapping

Linkage Disequilibrium Mapping
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Linkage Disequilibrium Mapping is a method used in genetics to locate genes associated with specific traits or diseases by examining the non-random association of alleles at different loci. This technique leverages the concept of linkage disequilibrium (LD), which refers to the non-random association of alleles at two or more loci.

Background

Linkage disequilibrium occurs when alleles at different loci are found together more often than would be expected by chance. This phenomenon can arise due to several factors, including genetic linkage, population structure, selection, and genetic drift. LD is a crucial concept in population genetics and is extensively used in genome-wide association studies (GWAS).

Principles of Linkage Disequilibrium

Linkage disequilibrium is quantified by several statistical measures, including D' (D prime) and r^2. These measures help determine the strength and significance of the association between alleles at different loci. High LD between loci suggests that they are physically close on the chromosome and may be inherited together.

D' (D prime)

D' is a measure of the deviation of the observed frequency of a particular haplotype from the expected frequency under the assumption of linkage equilibrium. It ranges from 0 to 1, where 1 indicates complete linkage disequilibrium.

r^2

r^2 is the squared correlation coefficient between alleles at two loci. It provides information about the predictability of one allele based on the presence of another. An r^2 value close to 1 indicates strong linkage disequilibrium.

Applications of Linkage Disequilibrium Mapping

Linkage disequilibrium mapping is widely used in identifying genetic variants associated with complex traits and diseases. It is a powerful tool in the field of genomics and has several applications:

Genome-Wide Association Studies (GWAS)

GWAS utilize linkage disequilibrium mapping to identify single nucleotide polymorphisms (SNPs) associated with diseases. By scanning the genome for SNPs that show significant association with a trait, researchers can pinpoint regions of interest for further study.

Fine Mapping

Once a region of interest is identified through GWAS, linkage disequilibrium mapping can be used for fine mapping to narrow down the specific genetic variants responsible for the trait.

Haplotype Mapping

Haplotype mapping involves studying combinations of alleles or SNPs that are inherited together. Linkage disequilibrium mapping helps in identifying these haplotypes and understanding their role in disease susceptibility.

Challenges and Limitations

While linkage disequilibrium mapping is a powerful tool, it has several challenges and limitations:

Population Stratification

Population stratification can lead to spurious associations if not properly controlled. It occurs when there are systematic differences in allele frequencies between subpopulations.

Resolution Limitations

The resolution of linkage disequilibrium mapping is limited by the extent of LD in the population. In populations with low LD, it may be challenging to pinpoint causal variants.

Complex Traits

For complex traits influenced by multiple genes and environmental factors, linkage disequilibrium mapping may not fully capture the genetic architecture.

Conclusion

Linkage disequilibrium mapping is a fundamental technique in modern genetics, providing insights into the genetic basis of diseases and traits. Despite its challenges, it remains a cornerstone of genetic research and continues to evolve with advancements in genomic technologies.

See Also

• Genetic linkage
• Genome-wide association study
• Haplotype
• Single nucleotide polymorphism