Friday 14 July 2017

Genetic linkage greater than 50 centimorgans


Classically, the linkage between two loci can be measured in centimorgans (cM), which represents the percent chance that these two loci will recombine an odd number of times (generating a recombinant genotype).



Due to independent assortment, markers on different chromosomes are expected to recombine 50% of the time. As I understand, if one conducts a classic experiment and counts various progeny, then deduces the apparent linkage, values of 50 cM or more are interpreted as "impossible to determine whether on separate chromosomes or just recombines very often". See (source), with grammar corrected:



The final point that we need to make regards the maximum distance that we can measure. Because of the way in which the calculations are performed, we can never have more (than) 50% recombinant gametes. Therefore the (maximum) distance that two genes can be apart and still measure that distance is just less (than) 50 cM. If two genes are greater than 50 cM apart, then we can not determine if they reside on the same chromosome or are on different chromosomes.



Wikipedia gives an analytical solution and also remarks that (d is physical distance):



The probability of recombination is approximately d/100 for small values of d and approaches 50% as d goes to infinity.



However, what happens if the linkage is greater than 50 cM? It seems like classical experiments aside, such a situation is possible in reality.


For instance, yeast chromosome IV is 1530 kb long, and averages 0.31 cM/kbp. Let's take two genes on Chr.IV:




  • DNF2 is at about +631 kb.

  • TOM1 is at about +1370 kb.


The physical distance between these is about 734 kb. According to the cM/kbp value, the centimorgan distance is $734\text{ kb} \cdot 0.31\text{ cM}/\text{kb} = 228 \text{ cM}$ . How to interpret this 228?


If I mate a haploid yeast which is DNF2 TOM1 with another which is dnf2 tom1 (lowercase indicating minor allele rather than deletion), then sporulate them, what is the chance of getting spores with DNF2 tom1 or dnf2 TOM1 genotypes?


I realize that the cM/kbp value is only a simplification and that in practice linkage is a more complex phenomenon. Nevertheless, it seems plausible that several crossover events can happen on Chr.IV since it is so big. This includes the possibility of 1, 3, 5 and more crossovers which would create a hybrid (assuming they all happen between these two loci), as well as the possibility of 2, 4, etc crossovers which would create a non-hybrid spore (at least as far as our chosen markers are concerned).




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