Linkage versus Linkage-Disequilibrium

This is a personal note which may contain nonsense. If you find major errors, please let me know (W.Li, wli@linkage.rockefeller.edu, Jan 08, 1999).

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?).