Recombination frequencies

The chiasma graph method (Wada and Imai, 1995) has been used to examine the frequency and chromosomal distribution of chiasma on 

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Zavattari P, Deidda E, Whalen M et al. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations demography, chromosome recombination frequency and selection. Hum Mol Genet 2000 9 2947-2957. 

Centimorgan (cM) The recombination frequency is measured in centimorgans. One cM is equal to a 1% chance that a marker at one genetic locus will be separated from a marker at a second locus by crossing over (in a single generation). One cM is equivalent, on average, to 1 million base pairs in humans. 

The distance between two loci can be inferred by estimating the frequency with which crossovers occur between them. Because this is done by looking at recombinations in families, we refer to this as a recombination frequency. 

Examination of the offspring in generation 3 shows that our prediction is met in all cases but one the last son in the pedigree has a 1,1 genotype but is unaffected. We infer that a crossover occurred in the chromosome transmitted from the mother to this offspring. Thus, on the basis of the limited information provided by this family, we estimate the recombination frequency to be one sixth, or about 17%. In other words, we predict that, about 17% of the time, a crossover will occur between the marker locus and the disease locus. In practice, a much larger sample of families is used to provide a more accurate estimate of the recombination frequency. If the recombination frequency is estimated to be 50%, the two loci are unlinked and may be on different chromosomes. 

The recombination frequency provides a measure of the genetic distance between any pair of linked loci. Genetic distances are often expressed in centiMorgans (cM). One centiMorgan is equal to a 1% recombination frequency between two loci (for example, two loci that are 10 cM apart would have a recombination frequency of 10%). Physically, 1 cM is approximately equal to 1 million base pairs of DNA (1 Mb). This relationship is only approximate, however, because crossover frequencies vary somewhat throughout the genome (e.g., crossovers are less common near centromeres and more common near telomeres). 

In the example given above, it is quite possible that because of the small size of our sample, the two loci only appear to be linked at 17 cM—the result could easily have been obtained simply by chance. To estimate the likelihood that two loci are truly linked with a specific recombination frequency, a LOD score is used. The LOD ( log of the odds ) is estimated as ... 

The value of 6 at which the highest LOD score is seen is the most likely estimate of the recombination frequency. 

Figure 11-4-3. Duration of Linkage Disequilibrium as a Function of Time for Loci Showing Different Recombination Frequencies (6)...

Nelson, O. E. 1%2. The waxy locus in maize. I. Intralocus recombination frequency estimates by pollen and by conventional analyses. Genetics 47, 737-742. 

Abbs S, Roberts RG, Mathew CG, Bentley DR, Bobrow M. Accurate assessment of intragenic recombination frequency within the Duchenne muscular dystrophy gene. Genomics 1990 7 602-6. 

While all these protocols lead to random recombination of a set of parental genes, the protocols vary in their ability to work on DNA fragments of different lengths, in their homology requirements, and how accurately they can be tuned in terms of recombination frequency and recombination sites within a gene. The RCR protocol, for example, allows the practitioner - due to its cyclic nature - to adjust both the number of recombination events and the recombination sites (see Fig. 1.2 for details). The experimental choice of recombination sites and events becomes valuable when, for example, sets of synergistic mutations have already been identified... 

The mouse Igh locus is located on the telomeric end of chromosome 12 [91]. However, the orientation of the heavy chain locus is controversial. The order cen-tromere-VH-CH was originally proposed based on recombination frequencies [92] and an analysis of the Harwell translocation T(5 12)31H [91]. More recently, a mouse plasmacytoma (J558) carrying a translocation between the Igh locus on chromosome 12 and the c-myc locus on chromosome 15 has been fused with Chinese hamster cells by Erikson et al. [93]. These investigators concluded that the orientation of the mouse Igh locus is centromere-CH-VH. Additional studies will be necessary to resolve this point. 

Fiq. 3. Map of mutant sites based on frequencies of am recombinants in N. crassa. Amino acid replacements of am (residue 141) and am7 (residue 142) cannot be aligned by recombination frequency (see text). 

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