Genetic Linkage - LOD Score Method For Estimating Recombination Frequency

LOD Score Method For Estimating Recombination Frequency

The LOD score (logarithm (base 10) of odds), developed by Newton E. Morton, is a statistical test often used for linkage analysis in human, animal, and plant populations. The LOD score compares the likelihood of obtaining the test data if the two loci are indeed linked, to the likelihood of observing the same data purely by chance. Positive LOD scores favor the presence of linkage, whereas negative LOD scores indicate that linkage is less likely. Computerized LOD score analysis is a simple way to analyze complex family pedigrees in order to determine the linkage between Mendelian traits (or between a trait and a marker, or two markers).

The method is described in greater detail by Strachan and Read . Briefly, it works as follows:

  1. Establish a pedigree
  2. Make a number of estimates of recombination frequency
  3. Calculate a LOD score for each estimate
  4. The estimate with the highest LOD score will be considered the best estimate

The LOD score is calculated as follows:

\begin{align} LOD = Z & = \log_{10} \frac{ \mbox{probability of birth sequence with a given linkage value} }{ \mbox{probability of birth sequence with no linkage} } \\ & = \log_{10} \frac{(1-\theta)^{NR} \times \theta^R}{ 0.5^{(NR + R)} } \end{align}

NR denotes the number of non-recombinant offspring, and R denotes the number of recombinant offspring. The reason 0.5 is used in the denominator is that any alleles that are completely unlinked (e.g. alleles on separate chromosomes) have a 50% chance of recombination, due to independent assortment.

Theta is the recombinant fraction, it is equal to R / (NR + R)

By convention, a LOD score greater than 3.0 is considered evidence for linkage. A LOD score of +3 indicates 1000 to 1 odds that the linkage being observed did not occur by chance. On the other hand, a LOD score less than -2.0 is considered evidence to exclude linkage. Although it is very unlikely that a LOD score of 3 would be obtained from a single pedigree, the mathematical properties of the test allow data from a number of pedigrees to be combined by summing the LOD scores. It is important to keep in mind that this traditional cutoff of LOD>+3 is an arbitrary one and that the difference between certain types of linkage studies, particularly analyses of complex genetic traits with hundreds of markers, these criteria should probably be modified to a somewhat higher cutoff.

Read more about this topic:  Genetic Linkage

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