Corelation Between Genetic Mapping And Physical Mapping

Corelation Between Genetic Mapping And Physical Mapping

Mapping By “Prime Complementation” –

  • If one had in hand a set of primes that carried the entire bacterial chromosome, one could mate them, one at a time, into a recipient with a particular mutation and look for the correction of that mutation by complementation or recombination. 
  • Presumably, only the primes carrying the region mutated in the recipient would be capable of correcting the mutant phenotype. 
  • If one thinks about this a bit, it is clear that this form of mapping is a version of deletion mapping where the majority of the chromosome is deleted. 
  • It can also be performed with smaller cloned regions on any replicating plasmid. 
  • This system works because most mutations cause loss of function and are therefore recessive to wild-type. 
  • This approach would fail in an attempt to map trans-dominant mutations.

Physical Mapping –

  • As noted at the start, it is becoming possible to cut an entire bacterial chromosome into a relatively few pieces (typically with restriction enzymes with unusually large, and therefore very infrequent, target sites) and then to identify the fragment that hybridizes to any cloned piece of DNA. 
  • Since the “marker” used is a hybridization probe, this allows mapping of regions of hybridization and rather than mutations, in contrast to genetic mapping. 
  • The physical mapping of a transposon insertion does both, however, because the hybridizing region is the mutation. 
  • When this approach has been performed on organisms with a preexisting body of genetic information available (e.g. E. coli), a very powerful genetic/physical composite map is generated. 
  • On the other hand, it is unclear to this observer, at least, how such information is of particular use in understanding organisms that lack such a history of genetic characterization, since it simply locates the cloned region on a vast featureless piece of DNA. 
  • This approach will certainly become easier as more “rarely-cutting” restriction enzymes become available and as tools are developed to introduce unique restriction sites into genomes.

Final Notes on Mapping –

  • The problem of “signal-to-noise ratio”, alluded to in the section on deletion mapping, is an important point. 
  • It should be remembered that most point mutations will revert at a reasonable frequency and for many mapping systems, these revertants will confuse the results and lower the potential resolution of the mapping system.
  • It should be reemphasized that genetic mapping, and particularly deletion mapping, establishes genetic, and not physical, distances (though rough estimates are possible through use of certain numerical analyses). 
  • Just because one finds more mutations in a particular region of a gene, as defined by deletion mapping, one should not assume that region is large. 
  • It could simply be that region of the protein is critical, so that a disproportionate fraction of point mutations are detected there. 
  • Consequently, this allows you to separate the region into more deletion intervals because the end points of more deletions are separable.
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