Linkage disequilibrium $\left(D\right)$ for two bi-allelic loci is defined as:

$$D=X_{11}X_{22} - X_{12}X_{21}$$

where $X_{11},\ X_{12},\ X_{21},\ X_{22}$ are the frequencies of the haplotypes $A_1B_1$, $A_1B_2$, $A_2B_1$, $A_2B_2$ respectively (the subscript number correspond to the two different alleles and $A$ and $B$ correspond to the two different loci)

My questions are

  • How is $D$ defined for more loci and a greater number of alleles?

  • How is $D$ defined when the number of alleles differ from locus to locus?

  • $\begingroup$ Let me know if my answer is making sense to you $\endgroup$
    Commented Nov 21, 2014 at 16:16

2 Answers 2


LD describes the associations among alleles at different loci. For anything more than two bi-allelic loci, you need more than just one number to fully describe the associations. For instance, if we have three bi-allelic loci 1-3, we need the three pairwise LD coefficients, plus one extra three-way coefficient. In general, if we have $K$ loci, and the $k^\text{th}$ locus has $n_k$ alleles, there are $\prod_k n_k$ possible haplotypes, so to fully describe the state of the population we need $\prod_k n_k-1$ haplotype frequencies. If we instead want to use allele frequencies and associations, we'll therefore need $$\prod_k n_k-1-\sum_k(n_k-1)=\prod_k n_k-\sum_k n_k+k-1$$ LD coefficients. (Note that each locus is described by $n_k-1$ allele frequencies.) This means that things get complicated pretty quickly with many loci! If you want to dive into the details, check out Barton and Turelli (1991) and Kirkpatrick, Johnson, and Barton (2002).


Being a typical molecular biologist, I am a little uncomfortable with classical genetics terms. I might redefine some symbols (perhaps to mean the same) [It is like talking to oneself while thinking].

There are four DNA-blocks : A1, B1, A2 and B2. Ak and Bk are adjacent blocks. [Perhaps this is same as what you defined the symbols as]. A and B are contiguous DNA regions whereas 1 and 2 are different chromosomes (homologous regions). See the figure below.

                                    enter image description here

The formula:

D=X11X22 - X12X21

basically means that the difference between the probability that the loci are in configuration I (11 & 22) or configuration II (swapped) (12 & 21). Lets say there is a third region (3) which is homologous to the two alleles which has DNA-blocks A3 and B3.

As LD is defined it is a difference in probabilities. Depending on how you define, it will take a negative or a positive value. When you have 3 recombinationally feasible alleles then there can be six cases:

  1. C1: [A1B1] [A2B2] [A3B3]
  2. C2: [A1B1] [A2B3] [A3B2]
  3. C3: [A1B3] [A2B2] [A3B1]
  4. C4: [A1B2] [A2B1] [A3B3]
  5. C5: [A1B2] [A2B3] [A3B1]
  6. C6: [A1B3] [A2B1] [A3B2]

In this case there is no single measure for difference. You can also do something like this:

LD1' = P(C1) + P(C2) - (P(C3) + P(C4) + P(C5) + P(C6))

Where LD1' is LD of region 1 and P(Cm) is the frequency of mth configuration.

Now, if there are 3 or more adjacent DNA blocks, you can only define LD, pairwise. It however, makes sense because linkage reduces with distance and you can calculate LDAC = LDAB x LDBC
(A,B and C are contiguous in alphabetical order. If A and B are not linked then A and C cannot be linked.)


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