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In: Biology

Mention the application of linkage disequilibrium to identify disease alleles.

Mention the application of linkage disequilibrium to identify disease alleles.

Solutions

Expert Solution

Linkage disequilibrium (LD):

  • This is also known as gametic phase disequilibrium.
  • This is defined as the non random association of alleles at different loci in a given population.
  • When a mutation event results in a new allele on a specific chromosome in a person  then the linkage disequilibrium happens to occur.
  • As a result, the allelic combinations of the concerned loci observed in the population deviate significantly from frequencies expected on the basis of independent assortment.

Application of linkage disequilibrium to identify disease alleles:

  • The concept of linkage disequilibrium is important as it allows the identification of genetic markers that tag the actual causal variants.
  • Example of linkage disequilibrium is between HLA-A1 and B8 alleles .
  • Single nucleotide polymorphism (SNPs), across the genome reveals the complex genetic architecture for linkage disequilibrium.
  • These contiguous SNPs are grouped into clusters of varying size in which the SNPs in any one cluster show high levels of LD with each other but not with SNPs outside the cluster.
  • Example, the 9 polymorphic loci in cluster 1 consists of 2 alleles, which have the potential to generate 29 which is equal to 512 different haplotypes, but only 5 haplotypes consists of 98% of all haplotypes seen. 
  • Clusters of loci with alleles in high LD across segments of only a few kilobase pairs to a few dozen kilobase pairs are termed as LD blocks.

 


 Linkage: 

  • Linkage is the phenomenon of certain genes staying together during inheritance through generations without change or separation as they on the same chromosomes.
  • This phenomenon is thought to be as exception of independent assortment.

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