linkage studies

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Amritha Nair
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linkage studies

can anyone explain the difference between linkage and linkage disequilibrium?

atcg
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In population genetics,

In population genetics, linkage disequilibrium is the non-random association of alleles at two or more loci, not necessarily on the same chromosome. It is not the same as linkage, which describes the association of two or more loci on a chromosome with limited recombination between them. Linkage disequilibrium describes a situation in which some combinations of alleles or genetic markers occur more or less frequently in a population than would be expected from a random formation of haplotypes from alleles based on their frequencies. Non-random associations between polymorphisms at different loci are measured by the degree of linkage disequilibrium (LD).

Linkage disequilibrium is generally caused by genetic linkage and the rate of recombination; rate of mutation; random drift or non-random mating; and population structure. For example, some organisms (such as bacteria) may show linkage disequilibrium because they reproduce asexually and there is no recombination to break down the linkage disequilibrium.
http://en.wikipedia.org/wiki/Linkage_disequilibrium

Both linkage and linkage-disequilibrium (LD) measures a correlation, or co-segregation, or association, between a genetic marker and the disease affection status. People do not even agree on a common operation definition. The situation can become confusing enough that it is not even possible to communicate with another colleague. Here I try to distinguish the two even without giving an operational definition.

1. Linkage focuses on a locus, Linkage-Disequilibrium focused on an allele

2. Linkage is resulted from recombination events in the last 2-3 generations, Linkage-Disequilibrium is resulted from much earlier, ancestral recombination events

3. Linkage measures co-segregation in a pedigree, Linkage-Disequilibrium measures co-segregation in a population (essentially a huge huge pedigree)

4. From the dynamical system point of view, Linkage is the "dynamical equation", Linkage-Disequilibrium is the "initial condition"

(ok, this may not be a familiar topic to people in genetics, but for people who knows differential equation, say, the equation that describes the motion of the Earth around the Sun, to predict the location of the Earth at any time, you need to know both the equation itself and the initial condition. since linkage-disequilibrium reflects ancestral recombination events, it provides a starting point to the current recombination events, something like the initial condition.)

5. In a pedigree likelihood (LOD score) calculation, the result tells you whether you have Linkage or not, Linkage-Disequilibrium, on the other hand, is provided by the user before the calculation (similar to the allele frequency, which should be provided in order to do the calculation).

6. Linkage is usually detected for markers reasonable close to the disease gene (one centiMorgan? one Mb?) , Linkage-Disequilibrium is detected for markers even closer (0.01-0.02 centiMorgan? 10-20 kB?).
http://linkage.rockefeller.edu/wli/lld.html

Hope this helps!

Amritha Nair
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hi jamie

hi jamie
thanks a lot for the info.. it really did help... i was wondering if u could point out certain references [books, sites etc.] that i could use to learn more