9-28-05

CHROMOSOMAL MAPS AND MAPPING FUNCTIONS

Any particular gene has a specific location (its "locus") on a particular chromosome. For any two genes (or loci) alpha and beta, we can ask "What is the recombination frequency between them?" If the genes are on different chromosomes, the answer is 50% (independent assortment). If the two genes are on the same chromosome, the recombination frequency will be somewhere in the range from 0 to 50%. The "map unit" (1 cM) is the genetic map distance that corresponds to a recombination frequency of 1%. In large chromosomes, the cumulative map distance may be much greater than 50cM, but the maximum recombination frequency is 50%. Why? In large chromosomes, there is enough length to allow for multiple cross-overs, so we have to ask what result we expect for random multiple cross-overs.


1. How is it that random multiple cross-overs give the same result as independent assortment?


Figure 5.12 shows how the various double cross-over possibilities add up, resulting in gamete genotype percentages that are indistinguisable from independent assortment (50% parental type, 50% non-parental type). This is a very important figure. It provides the explanation for why genes that are far apart on a very large chromosome sort out in crosses just as if they were on separate chromosomes.



2. Is there a way to measure how close together two crossovers can occur involving the same two chromatids? That is, how could we measure whether there is spacial "interference"?


Figure 5.13 shows how a measurement of the gamete frequencies resulting from a "three point cross" can answer this question. If we would get a "lower than expected" occurrence of recombinant genotypes aCb and AcB, it would suggest that there is some hindrance to the two cross-overs occurring this close together. Crosses of this type in Drosophila have shown that, in this organism, double cross-overs do not occur at distances of less than about 10 cM between the two cross-over sites. ( Textbook, page 196. )


3. How does all of this lead to the "mapping function", the mathematical (graphical) relation between the observed recombination frequency (percent non-parental gametes) and the cumulative genetic distance in map units?

Figure 5.14 shows the result for the two extremes of "complete interference" and "no interference". The situation for real chromosomes in real organisms is somewhere between these extremes, such as the curve labelled "interference decreasing with distance".

 

 

Note concerning tetrad analysis being done in lab this week.

In some species of fungi, the four gametes (the tetrad) resulting from meiosis are held in a sac-like structure called an ascus. Thus, all four haploid cells resulting from single meiotic processes can be analyzed; this is called "tetrad analysis". In some fungal species, the haploid gametes are present in an ordered array in the ascus. This is the case for Neurospora crassa and for Sordaria fimicola, allowing one to "see" the effects of crossing-over in the region between a gene alpha and the centromere of the chromosome that contains the gene. This is the analysis you are doing in the Genetics Lab course this week, so we will not cover it in detail here.





Problem S-7: "Human Genome Recombination Map"


Go to the article Kong et al., "A high-resolution recombination map of the human genome", Nature Genetics 31, 241-247 (2002). Print out a copy of Table 1; "Physical and genetic lengths of individual chromosomes", and answer the following questions from the data in the table.

a. Which human autosome is the smallest, and what is its physical length (rounded off)?

b. What is the genetic length (rounded off) of this smallest human autosome?

c. In this chromosome, approximately how far apart (in base pairs) are two genes alpha and beta that have a 1% recombination frequency between them?

d. Assuming that these two genes are of average size (as you calculated in problem S-1), draw the map of the section of this chromosome containing these two genes, showing the sizes of the genes and their distance apart in correct relative scale.

e. What does it mean that the numbers in the "male" and "female" genetic length columns are different?

f. How much variation is there from chromosome to chromosome in the likelihood of crossing-over?