Linkage Disequilibrium (Molecular Biology)

When the frequency of genotypes at more than two loci can be expressed as the cumulative product of the respective allele frequencies of each locus, those genes are said to be at the state of "linkage equilibrium." Suppose that two different loci, A and B, each have two alleles, A! and A2, and Bj and B2, respectively. Let us denote frequencies of alleles A1 and A 2 at locus A in a population as x1 and x2. Similarly, let us denote the allele frequencies at locus B as yl and y2. The genotypic frequency, X1, of A1 B1 (viz., allele A1 at locus A and allele B1 at locus B) can be expressed as X1 = x1y1 when those genes are at linkage equilibrium. When this relationship does not hold for some reason, those genes are said to be in a state of "linkage disequilibrium." Therefore, the linkage disequilibrium, D, can be measured by D (X1 – x1y1. When D = 0, linkage equilibrium exists (Fig. 1). Linkage disequilibrium usually occurs when a particular combination of alleles (a haplotype) is favored by or when two loci are located so closely on a chromosome that between those loci rarely takes place. It can also occur when equilibrium has not yet been reached in a population, or when there is nonrandom mating. When sampling in a finite population is nonrandom and produces an abundance of a particular haplotype, linkage disequilibrium will also be apparent. Favorable combinations of alleles will also be transmitted together at greater frequencies when they enhance reproduction and survival, leading to linkage disequilibrium.


Figure 1. Illustration of the calculation of linkage disequilibrium.

Illustration of the calculation of linkage disequilibrium.

Mechanisms that restrict recombination, such as asexual reproduction, promote the continuance of linkage disequilibrium, leading to the domination of a limited number of alleles. Linkage disequilibrium is also maintained through chromosomal translocations and inversions that reduce recombination. When natural selection favors linkage disequilibrium, chromosomal rearrangements will also increase the linkage. The so-called supergenes are closely linked genes that affect one or several related traits that have arisen through linkage disequilibrium.

With the advancement of technology, it will become possible to detect single-nucleotide polymorphisms, (SNP; pronounced "Snip"). By detecting SNP in the noncoding region of the gene of interest, one is able to detect which gene is responsible for a particular disease by checking if the linkage disequilibrium exists between a particular disease and SNP in a target population. This is one of the latest examples of utilization of linkage disequilibrium.

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