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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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The process of spontaneously occurring deletion must include two chromosome breaks to cut out the intervening segment. If the two ends join and one of them bears the centromere, a shortened chromosome results, which is said to carry a deletion. The deleted fragment is acentric; consequently it is immobile and will be lost. An effective mutagen for inducing chromosomal rearrangements of all kinds is ionizing radiation. This kind of radiation, of which X rays and γ rays are examples, is highly energetic and causes chromosome breaks. The way in which the breaks rejoin determines the kind of rearrangement produced. Two types of deletion are possible. Two breaks can produce an interstitial deletion, as shown in Figure 17-2. In principle, a single break can cause a terminal deletion; but, because of the need for the special chromosome tips (telomeres), it is likely that apparently terminal deletions include two breaks, one close to the telomere.

Figure 17-2. Terminal and interstitial deletions.

Figure 17-2

Terminal and interstitial deletions. Chromosome can be broken when struck by ionizing radiation (wavy arrows). A terminal deletion is the loss of the end of a chromosome. An interstitial deletion results after two breaks are induced if the terminal part (more...)

The effects of deletions depend on their size. A small deletion within a gene, called an intragenic deletion, inactivates the gene and has the same effect as other null mutations of that gene. If the homozygous null phenotype is viable (as, for example, in human albinism), then the homozygous deletion also will be viable. Intragenic deletions can be distinguished from single nucleotide changes because they are nonrevertible.

For most of this section, we shall be dealing with multigenic deletions, those that remove from two to several thousand genes. Multigenic deletions have severe consequences. If by inbreeding such a deletion is made homozygous (that is, if both homologs have the same deletion), then the combination is almost always lethal. This outcome suggests that most regions of the chromosomes are essential for normal viability and that complete elimination of any segment from the genome is deleterious. Even individuals heterozygous for a multigenic deletion—those with one normal homolog and one that carries the deletion—may not survive. There are several possible reasons for this failure to survive. First, a genome has been “fine tuned” during evolution to require a specific balance of genes, and the deletion upsets this balance. We shall encounter this balance notion several times in this chapter and the next, because several different types of chromosome mutations upset the ratio, or balance, of genes in a genome. Second, in many organisms there are recessive lethal and other deleterious mutations throughout the genome. If “covered” by wild-type alleles on the other homolog, these recessives are not expressed. However, a deletion can “uncover” recessives, allowing their expression at the phenotypic level.


The lethality of heterozygous deletions can be explained by genome imbalance and by unmasking of recessive lethal alleles.

Nevertheless, some small deletions are viable in combination with a normal homolog. In these cases, the deletion can sometimes be identified by cytogenetic analysis. If meiotic chromosomes are examined in an individual carrying a heterozygous deletion, the region of the deletion can be determined by the failure of the corresponding segment on the normal homolog to pair, resulting in a deletion loop (Figure 17-3a). In insects, deletion loops are detected in the polytene chromosomes, in which the homologs are fused (Figure 17-3b). A deletion can be assigned to a specific chromosome location by determining which chromosome shows the deletion loop and the position of the loop along the chromosome.

Figure 17-3. Looped configurations in a Drosophila deletion heterozygote.

Figure 17-3

Looped configurations in a Drosophila deletion heterozygote. In the meiotic pairing, the normal homolog forms a loop. The genes in this loop have no alleles with which to synapse. Because polytene chromosomes in Drosophila have specific banding patterns, (more...)

Deletions of some chromosomal regions produce their own unique phenotypes. A good example is a deletion of one specific small chromosome region of Drosophila. When one homolog carries the deletion, the fly shows a unique notch-wing phenotype, so the deletion acts as a dominant mutation in this regard. But the deletion is lethal when homozygous and therefore acts as a recessive in regard to its lethal effect. The specific dominant phenotypic effect of certain deletions might be caused by one of the chromosome breaks being inside a gene, which, when disrupted, will act as a dominant mutation.

What are the genetic properties of deletions? In addition to cytogenetic criteria, there are several purely genetic criteria for inferring the presence of a deletion. These criteria are particularly useful in species whose chromosomes are not easily analyzed cytogenetically.

Two genetic criteria we have encountered already. The first is the failure of the chromosome to survive as a homozygote; however, this effect could also be produced by any lethal mutation. Second, chromosomes with deletions can never revert to a normal condition. This criterion is useful only if there is some specific phenotype associated with the deletion.

A third criterion is that, in heterozygous deletions, recombinant frequencies between genes flanking the deletion are lower than in control crosses. This makes intuitive sense because part of the region contains an unpaired chromosomal region, which cannot participate in crossing-over. We will see that inversions have a similar effect on recombinant frequencies but can be distinguished in other ways.

A fourth criterion for inferring the presence of a deletion is that deletion of a segment on one homolog sometimes unmasks recessive alleles present on the other homolog, leading to their unexpected expression. Consider, for example, the deletion shown in the following diagram:

Image ch17fu6.jpg

In this case, none of the six recessive alleles is expected to be expressed, but, if b and c are expressed, then a deletion is suggested to have occurred on the other homolog spanning the b+ and c+ loci. Because in such cases it seems that recessive alleles are showing dominance, the effect is called pseudodominance.

The pseudodominance effect can also be used in the opposite direction. A known set of overlapping deletions is used to locate the map positions of new mutant alleles. This procedure is called deletion mapping. An example from the fruit fly Drosophila is shown in Figure 17-4. In this diagram, the recombination map is shown at the top, marked with distances in map units from the left end. The horizontal bars below the chromosome show the extent of the deletions identified at the left. The mutation prune (pn), for example, shows pseudodominance only with deletion 264-38, which determines its location in the 2D-4 to 3A-2 region. However, fa shows pseudodominance with all but two deletions, so its position can be pinpointed to band 3C-7.

Figure 17-4. Locating genes to chromosomal regions by observing pseudodominance in Drosophila heterozygous for deletion and normal chromosomes.

Figure 17-4

Locating genes to chromosomal regions by observing pseudodominance in Drosophila heterozygous for deletion and normal chromosomes. The red bars show the extent of the deleted segments in 13 deletions. All recessive alleles spanned by a deletion will be expressed. (more...)

Deletion analysis makes it possible to compare a linkage map based on recombinant frequency with the chromosome map based on deletion mapping. By and large, where this comparison has been made, the maps correspond well—a satisfying cytological endorsement of a purely genetic creation.


Chromosome maps made by analyzing deletion coverage are congruent with linkage maps made by analyzing recombinant frequency.

Image ch17fu7.jpg

Moreover, pseudodominance can be used to map a small deletion that cannot be visualized microscopically. Let’s consider an X chromosome in Drosophila that carries a recessive lethal suspected of being a deletion; we call this chromosome “X*.” We can cross X*-bearing females with males carrying recessive alleles of loci on that chromosome. For example, a map of loci in the tip region is

Image ch17e1.jpg

Suppose we obtain all wild-type flies in crosses between X*/X females and males carrying y, dor, br, gt, rst, and vt but obtain pseudodominance of swa and w with X* (that is, X*/swa shows the recessive swa phenotype and X*/w shows the recessive w phenotype). Then we have good genetic evidence for a deletion of the chromosome that includes at least the swa and w loci but not gt or rst.


Deletions are recognized genetically by (1) reduced RF, (2) pseudodominance, (3) recessive lethality, and (4) lack of reverse mutation and cytologically by (5) deletion loops.

Clinicians regularly find deletions in human chromosomes. In most cases, the deletions are relatively small, but they nevertheless have an adverse phenotypic effect, even though heterozygous. Deletions of specific human chromosome regions cause unique syndromes of phenotypic abnormalities. An example is the cri du chat syndrome, caused by a heterozygous deletion of the tip of the short arm of chromosome 5 (Figure 17-5). It is the convention to call the short arm of a chromosome p and to call the long arm q. The specific bands deleted in cri du chat syndrome are 5p15.2 and 5p15.3, the two most distal bands identifiable on 5p. The most characteristic phenotype in the syndrome is the one that gives it its name, the distinctive catlike mewing cries made by infants with this deletion. Other phenotypic manifestations of the syndrome are microencephaly (abnormally small head) and a moonlike face. Like syndromes caused by other deletions, the cri du chat syndrome also includes mental retardation.

Figure 17-5. The cause of the cri du chat syndrome of abnormalities in humans is loss of the tip of the short arm of one of the homologs of chromosome 5.

Figure 17-5

The cause of the cri du chat syndrome of abnormalities in humans is loss of the tip of the short arm of one of the homologs of chromosome 5.

Most human deletions, such as those that we have just considered, arise spontaneously in the germ line of a normal parent of an affected person; thus no signs of the deletions are found in the somatic chromosomes of the parents. However, as we shall see in a later section, some human deletions are produced by meiotic irregularities in a parent heterozygous for another type of rearrangement. Cri du chat syndrome, for example, can result from a parent heterozygous for a translocation.

Geneticists have mapped human genes from deletions by using a molecular technique called in situ hybridization. This technique was introduced in Chapters 3 and 6, but for now we can review the basics to show the usefulness of deletions. If an interesting gene or other DNA fragment has been isolated with the use of modern molecular technology, it can be tagged with a radioactive or chemical label and then added to a chromosomal preparation under the microscope. In such a situation, the DNA recognizes and physically binds to its normal chromosomal counterpart by nucleotide pairing and is recognized as a spot of radioactivity or dye. The precise location of such spots is difficult to correlate with specific bands, but the deletion technique comes to the rescue. If a deletion happens to span the locus in question, no spot will appear when the test is run with the chromosome carrying the deletion, because the region for binding simply is not present (Figure 17-6). By saving cell lines from patients with deletions, geneticists develop test panels of overlapping deletions spanning specific chromosomal regions, and these test panels can be used to pinpoint a gene’s position. An example from chromosome 11 is shown in Figure 17-7. The extent of the deletions in the test panel are shown as vertical bars, and the coded DNA fragments under test are shown at the right. If fragment 270, for example, failed to bind to deletions 35, 8, 10, 7, 9, 23, 24, A2, 27A, and 4D but did bind to the other deletions, it can be inferred that this piece of DNA originally came from the region spanned by 11q13.5 and 11q21.

Figure 17-6. Radioactive spots show up on only one chromosome 11, because the other one has a deletion in the region where the radioactive DNA binds.

Figure 17-6

Radioactive spots show up on only one chromosome 11, because the other one has a deletion in the region where the radioactive DNA binds.

Figure 17-7. Human DNA fragments mapped to regions of chromosome 11 by their failure to bind to particular deletions.

Figure 17-7

Human DNA fragments mapped to regions of chromosome 11 by their failure to bind to particular deletions. The red bars show the extent of the deletions, and the DNA fragments that were mapped are identified at the right. Notice that fragment 270, for example, (more...)

Chromosome mutations often arise in cancer cells, and we shall see several cases in this chapter and the next. As an example, Figure 17-8 shows some deletions consistently found in solid tumors. Not all the cells in a tumor show the deletion indicated, and often a mixture of different chromosome mutations can be found in one tumor. The contribution of such changes to the cancer phenotype is not understood.

Figure 17-8. Deletions found consistently in several different types of solid tumors in humans.

Figure 17-8

Deletions found consistently in several different types of solid tumors in humans. Band numbers indicate recurrent breakpoints. (After Jorge Yunis.)

An interesting difference between animals and plants is revealed by deletions. A male animal that is heterozygous for a deletion chromosome and a normal one produces functional sperm carrying each of the two chromosomes in approximately equal numbers. In other words, sperm seem to function to some extent regardless of their genetic content. In diploid plants, on the other hand, the pollen produced by a deletion heterozygote is of two types: (1) functional pollen carrying the normal chromosome and (2) nonfunctional (or aborted) pollen carrying the deficient homolog. Thus, pollen cells seem to be sensitive to changes in amount of chromosomal material, and this sensitivity might act to weed out deletions. The situation is somewhat different for polyploid plants, which are far more tolerant of pollen deletions. This tolerance is due to the fact that even the pollen carries several chromosome sets, and the loss of a segment in one of these sets is less crucial than it would be in a haploid pollen cell. Ovules in either diploid or polyploid plants also are quite tolerant of deletions, presumably because of the nurturing effect of the surrounding maternal tissues.

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: NBK21904


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