Download Notes on Haldane`s mapping function and physical and recomb maps

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Transcript
Haldane’s mapping function was designed to correct for “unseen” crossovers. Since there is the
possibility that double crossovers can occur between two genes, Haldane designed a mapping
function which attempts to include these multiple crossover events between two genes.
Haldanes mf = -0.5 x ln (1-2 x r), express as a percent to get a value in cM.
Here r is the usual proportion of recombinants estimate from a testcross.
If you multiply Haldane’s mf value by 100 that will provide you with an estimate of distance in cM.
A graph of the difference in our usual mapping approach versus Haldane's function is shown
below.
Haldane's mapping function
200
180
Haldane or RF
160
140
120
Haldane's
100
RF(cM)
80
60
40
20
0
0
0.2
0.4
0.6
recomb prop (r)
You can see that for small values of recombination (say less than about 0.2) the two approaches
give similar mapping distances. As r increases, there is an increasing difference between the two
mapping approaches.
Physical maps vs recombination maps.
Thus far we've considered genetic maps drawn based upon recombination frequencies to
determine gene orders and distances between them. Sometimes we also have, or certainly want a
physical map. Physical maps involve measuring the distances between genes in terms of the
numbers of basepairs of DNA. These can be obtained through sequencing of the entire genome,
as for many model organisms (or sequencing a portion of the genome of interest).
The gene order of both maps should be identical. The distances between genes in the two maps
are measured with different units (RF versus bp or kb or mb). Also, the differences in the
distances between genes may differ between the recombination versus the physical map. That is
because recombination isn't random across a chromosome. There may be hotspots or cold spots
for recombination. For example, regions near the centromeres often have few recombination
events in them. Thus in those regions there will be more DNA distances between a pair of genes
but a smaller distance as determined by recombination maps.
Often, an advantage of having both maps is that the with a recombination map you can identify
molecular markers linked to a gene determining a phenotype of interest. The molecular marker
positions can also be identified on the physical map as well since we typically know the gene
sequence of the marker. Given this information, you will then know that the gene causing the
phenotype of interest must lie somewhere between your two markers of interest.
recomb map
physical map
M1
gene1
.1cM M2
gene2
gene3
.2cM
trait
gene4
.2cM
gene5
M3
gene6
M4
gene7
gene8 100 kb
so here we can see that RFLP markers M2 and M3 lie on opposite sides of a gene determining
the trait of interest. Since we know the location of the markers on the physcial map we can
essentially align the two maps. We can see that four genes lie between those two markers.
Gene3, Gene 4, Gene 5 and Gene 6, all of which could be considered candidates for determining
the trait of interest. If we continue to map more markers in the interval between M2 and M3, we
can perhaps continue to exclude some of the candidate genes. We can also use other approaches
to determine which of the candidate genes might be resonsible for the trait of interest.