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Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th edition. New York: W. H. Freeman; 2000.

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An Introduction to Genetic Analysis. 7th edition.

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Linkage maps

The frequency of recombinants for the Drosophila autosomal genes that we studied (pr and vg) was 10.7 percent of the progeny—a frequency much greater than that for the linked genes on the X chromosome just studied. Apparently, the amount of crossing-over between various linked genes differs. Indeed, there is no reason to expect that chromatids would cross over between different linked genes with the same frequency. As Morgan studied more linked genes, he saw that the proportion of recombinant progeny varied considerably, depending on which linked genes were being studied, and he thought that these variations in crossover frequency might somehow indicate the actual distances separating genes on the chromosomes. Morgan assigned the study of this problem to a student, Alfred Sturtevant, who (like Bridges) became a great geneticist. Morgan asked Sturtevant, still an undergraduate at the time, to make some sense of the data on crossing-over between different linked genes. In one night, Sturtevant developed a method for describing relations between genes that is still used today. In Sturtevant’s own words, “In the latter part of 1911, in conversation with Morgan, I suddenly realized that the variations in strength of linkage, already attributed by Morgan to differences in the spatial separation of genes, offered the possibility of determining sequences in the linear dimension of a chromosome. I went home and spent most of the night (to the neglect of my undergraduate homework) in producing the first chromosome map.”

As an example of Sturtevant’s logic, consider a testcross from which we obtain the following results:

Image ch5e11.jpg

The progeny in this example represent 400 female gametes, of which 44 (11 percent) are recombinant. Sturtevant suggested that we can use the percentage of recombinants as a quantitative index of the linear distance between two genes on a genetic map, or linkage map, as it is sometimes called.

The basic idea here is quite simple. Imagine two specific genes positioned a certain fixed distance apart. Now imagine random crossing-over along the paired homologs. In some meiotic divisions, nonsister chromatids cross over by chance in the chromosomal region between these genes; from these meioses, recombinants are produced. In other meiotic divisions, there are no crossovers between these genes; no recombinants result from these meioses. Sturtevant postulated a rough proportionality: the greater the distance between the linked genes, the greater the chance that nonsister chromatids would cross over in the region between the genes and, hence, the greater the proportion of recombinants that would be produced. Thus, by determining the frequency of recombinants, we can obtain a measure of the map distance between the genes (Figure 5-9). In fact, we can define one genetic map unit (m.u.) as that distance between genes for which one product of meiosis in 100 is recombinant. Put another way, a recombinant frequency (RF) of 0.01 (1 percent) is defined as 1 m.u. [A map unit is sometimes referred to as a centimorgan (cM) in honor of Thomas Hunt Morgan.]

Figure 5-9. Proportionality between chromosome distance and recombinant frequency.

Figure 5-9

Proportionality between chromosome distance and recombinant frequency. In every meiosis, chromatids cross over at random along the chromosome. The two genes T and U are farther apart on a chromosome than V and W. Chromatids cross over between T and U (more...)

A direct consequence of the way in which map distance is measured is that, if 5 map units (5 m.u.) separate genes A and B whereas 3 m.u. separate genes A and C, then B and C should be either 8 or 2 m.u. apart (Figure 5-10). Sturtevant found this to be the case. In other words, his analysis strongly suggested that genes are arranged in some linear order.

Figure 5-10. Because map distances are additive, calculation of the A–B and A–C distances leaves us with the two possibilities shown for the B–C distance.

Figure 5-10

Because map distances are additive, calculation of the AB and AC distances leaves us with the two possibilities shown for the BC distance.

The place on the map—and on the chromosome—where a gene is located is called the gene locus (plural, loci). The locus of the eye-color gene and the locus of the wing-length gene, for example, are 11 m.u. apart. The relation is usually diagrammed this way:

Image ch5e12.jpg

although it could be diagrammed equally well like this:

Image ch5e13.jpg

or like this:

Image ch5e14.jpg

Usually we refer to the locus of this eye-color gene in shorthand as the “pr locus,” after the first discovered non-wild-type allele, but we mean the place on the chromosome where any allele of this gene will be found.

Given a genetic distance in map units, we can predict frequencies of progeny in different classes. For example, in the progeny from a testcross of a female prvg/pr+vg+ heterozygote, we know that there will be 11 percent recombinants, of which 5 1/2 percent will be prvg+/prvg and 5 1/2 percent will be pr+vg/pr vg; of the progeny from a testcross of a female pr vg+/pr+vg heterozygote, 5 1/2 percent will be pr vg/pr vg and 5 1/2 percent will be pr+vg+/pr vg.

There is a strong implication that the “distance” on a linkage map is a physical distance along a chromosome, and Morgan and Sturtevant certainly intended to imply just that. But we should realize that the linkage map is another example of an entity constructed from a purely genetic analysis. The linkage map could have been derived without even knowing that chromosomes existed. Furthermore, at this point in our discussion, we cannot say whether the “genetic distances” calculated by means of recombinant frequencies in any way represent actual physical distances on chromosomes, although cytogenetic and molecular analysis has shown that genetic distances are, in fact, roughly proportional to chromosome distances. Nevertheless, it must be emphasized that the hypothetical structure (the linkage map) was developed with a very real structure (the chromosome) in mind. In other words, the chromosome theory provided the framework for the development of linkage mapping.


Recombination between linked genes can be used to map their distance apart on the chromosome. The unit of mapping (1 m.u.) is defined as a recombinant frequency of 1 percent.

The stage of analysis that we have reached in our discussion is well illustrated by linkage maps of the screwworm (Cochliomyia hominivorax). The larval stage of this insect—the worm—is parasitic on mammalian wounds and is a costly pest of livestock in some parts of the world. A genetic system of population control has been proposed, of a type that has been successful in other insects. To accomplish this goal, an understanding of the basic genetics of the insect is needed, one important part of which is to prepare a map of the chromosomes. This animal has six chromosome pairs, and mapping has begun.

The job of general mapping starts by finding and analyzing as many variant phenotypes as possible. The adult stage of this insect is a fly, and geneticists have found phenotypic variants among screwworm flies. They found flies of six different eye colors, all different from the brown-eyed, wild-type flies, as Figure 5-11a shows. They also found five variant phenotypes for some other characters. Eleven mutant alleles were shown to determine the 11 variant phenotypes, each at a different autosomal locus. Pure lines of each phenotype were intercrossed to generate dihybrid F1s, and then these were testcrossed. The testcross revealed the set of four linkage groups shown in Figure 5-11b. Notice that the ye and cw loci are shown tentatively linked, although the recombinant frequency is not significantly different from 50 percent.

Figure 5-11. (a) Wild-type adult of screwworm and six flies whose eye colors are determined by alleles at six different autosomal loci.

Figure 5-11

(a) Wild-type adult of screwworm and six flies whose eye colors are determined by alleles at six different autosomal loci. (b) Linkage maps of the six eye-color loci (highlighted) and five other loci of screwworms. The numbers between the loci give the (more...)

A linkage analysis such as the preceding one cannot assign linkage groups to specific chromosomes; this must be done by using the cytogenetic techniques to be considered in Chapter 17. In the present example, such cytogenetic techniques have allowed the linkage groups to be correlated with the chromosomes previously numbered as shown in Figure 5-11b.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2000, W. H. Freeman and Company.
Bookshelf ID: NBK21827


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