Genetic Linkage

Steps in Determining the Lod Score

1. Select a beginning recombination frequency (theta)

• pick theta= 0.125 based on the data from the pedigree

2. Determine the possible number of recombinants and possible number of parentals

• two parentals and two recombinants

3. Determine the probability of a parental or recombinant birth

• recombinant probability = theta/2 = 0.125/2 = 0.0625
• parental probability = (1 - theta)/= (1 - 0.125)/2 = 0.4375

4. Determine the probability of the given birth order given theta

• the probability of a birth sequence is the product of individual probabilities
• the example has seven parental and one recombinant births

               probability = (0.4375)7(0.0625)1

5. Determine the probability of a given birth without linkage

• the probability is 0.25 because without linkage the four genotypes are equally probable

                    probability = (0.25)8 = 0.0000153

6. Determine the Lod Score

                    Lod Score = log (0.0001917/0.0000153) = 1.099

7. Repeat the sequence of calculations with other q (linkage) values

Recombination Frequency(RF)	Lod Score
0.050	0.951
0.100	1.088
0.125	1.099
0.150	1.090
0.200	1.031
0.250	0.932

8. Select the theta that gives the highest lod score. That is your best linkage estimate.

                    Best estimate = 0.125 RF or 12.5 cM

Notes on the Lod Score Method

• In general, we try to obtain a lod score value of greater than 3.0. To obtain this we usually need larger sample sizes.
• We generally can report linkage distance based on a lod score less that three, but we need to mention this is our best estimate given the pedigree information available.