Hartl, Jones - Genetics. Principlers and analysis - 1998 (522927), страница 86
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The remainder of this chapter deals withabnormalities in chromosome structure. There are several principal types of structural aberrations, each of whichhas characteristic genetic effects. Chromosome aberrations were initially discovered through their genetic effects,which, though confusing at first, eventually came to be understood as resulting from abnormal chromosomestructure. This interpretation was later confirmed directly by microscopic observations.DeletionsA chromosome sometimes arises in which a segment is missing.
Such a chromosome is said to have a deletion or adeficiency. Deletions are generally harmful to the organism, and the usual rule is the larger the deletion, the greaterthe harm. Very large deletions are usually lethal, even when heterozygous with a normal chromosome. Smalldeletions are often viable when they are heterozygous with a structurally normal homolog, because the normalhomolog supplies gene products that are necessary for survival.
However, even small deletions are usuallyhomozygous lethal (lethal when both members of a pair of homologous chromosomes carry the deletion).Deletions can be detected genetically by making use of the fact that a chromosome with a deletion no longer carriesthe wild-type alleles of the genes that have been eliminated.
For example, in Drosophila, many Notch deletions arelarge enough to remove the nearby wildtype allele of white, also. When these deleted chromosomes areheterozygous with a structurally normal chromosome carrying the recessive w allele, the fly has white eyes becausethe wildtype w+ allele is no longer present in the deleted Notch chromosome. This uncovering of the recessiveallele implies that the corresponding wildtype allele of white has also been deleted.
Once a deletion has beenidentified, its size can be assessed genetically by determining which recessive mutations in the region areuncovered by the deletion. This method is illustrated in Figure 7.18.With the banded polytene chromosomes in Drosophila salivary glands, it is possible to study deletions and otherchromosome aberrations physically. For example, all the Notch deletions cause particular bands to be missing inthe salivary chromosomes.
Physical mapping of deletions also allows individual genes, otherwise known only fromgenetic studies, to be assigned to specific bands or regions in the salivary chromosomes.Physical mapping of genes in part of the Drosophila X chromosome is illustrated in Figure 7.19. The bandedchromosome is shown near the top, along with the num-Page 282bering system used to refer to specific bands. Each chromosome is divided into numbered sections (the Xchromosome comprises sections 1 through 20), and each of the sections is divided into subdivisions designated Athrough F.
Within each lettered subdivision, the bands are numbered in order, and so, for example, 3A6 is the sixthband in subdivision A of section 3 (Figure 7.19). On the average, each band contains about 20 kb of DNA, butthere is considerable variation in DNA content from band to band.In Figure 7.19, the mutant X chromosomes labeled I through VI have deletions. The deleted part of eachchromosome is shown in red. These deletions define regions along the chromosome, some of which correspond tospecific bands. For example, the deleted region in both chromosome I and II that is present in all the otherchromosomes consists of band 3A3.
In crosses, only deletions I and II uncover the mutation zeste (z), so the z genemust be in band 3A3, as indicated at the top. Similarly, the recessive-lethal mutation zw2 is uncovered by alldeletions except VI; therefore, the zw2 gene must be in band 3A9. As a final example, the w mutation is uncoveredonly by deletions II, III, and IV; thus the w gene must be in band 3C2. The rst (rough eye texture) and N (notchedwing margin) genes are not uncovered by any of the deletions. These genes were localized by a similar analysis ofoverlapping deletions in regions 3C5 to 3C10.DuplicationsSome abnormal chromosome have a region that is present twice.
These chromosomes are said to have aduplication.Figure 7.18Mapping of a deletion by testcrosses. The F1 heterozygotes with the deletion express the recessive phenotype of all deletedgenes. The expressed recessive alleles are said to be uncovered by the deletion.Page 283Figure 7.19Part of the X chromosome in polytene salivary gland nuclei of Drosophila melanogaster and theextent of six deletions (I–VI) in a set of chromosomes. Any recessive allele that is uncoveredby a deletion must be located inside the boundaries of the deletion. This principle can be used toassign genes to specific bands in the chromosome.Certain duplications have phenotypic effects of their own.
An example is the Bar duplication in Drosophila, whichis a tandem duplication of bands 16A1 through 16A7 in the X chromosome. A tandem duplication is one in whichthe duplicated segment is present in the same orientation immediately adjacent to the normal region in thechromosome. In the case of Bar, the tandem duplication produces a dominant phenotype of bar-shaped eyes.Tandem duplications are able to produce even more copies of the duplicated region by means of a process calledunequal crossing-over. Figure 7.20A illustrates the chromosomes in meiosis of an organism that is homozygousfor a tandem duplication (brown region). When they undergo synapsis, these chromosomes can mispair with eachother, as illustrated in Figure 7.20B. A crossover within the mispaired part of the duplication (Figure 7.20C) willthereby produce a chromatid carrying a triplication, and a reciprocal product (labeled "single copy" in Figure7.20D) that has lost the duplication.
For the Bar region, the triplication can be recognized because it produces aneven greater reduction in eye size than the duplication.The most frequent effect of a duplication is a reduction in viability (probability of survival); in general, survivaldecreases with increasing size of the duplication. However, deletions are usually more harmful than duplications ofcomparable size.Unequal Crossing-Over in Human Red-Green Color BlindnessHuman color vision is mediated by three light-sensitive protein pigments present in the cone cells of the retina.Each of the pigments is related to rhodopsin, the pigmentPage 284Figure 7.20An increase in the number of copies of a chromosome segment resulting from unequal crossing-over of tandem duplications(brown). (A) Normal synapsis of chromosomes with a tandem duplication.
(B) Mispairing. The right-hand element of thelower chromosome is paired with the left-hand element of the upper chromosome. (C) Crossing-over within the mispairedduplication, which is called unequal crossing-over. (D) The outcome of unequal crossing-over. One productcontains a single copy of the duplicated region, another chromosome contains a triplication, and the twostrands not participating in the crossover retain the duplication.that is found in the rod cells and mediates vision in dim light. The light sensitivities of the cone pigments aretoward blue, red, and green. These are our primary colors.
We perceive all other colors as mixtures of theseprimaries. The gene for the blue-sensitive pigment resides somewhere in 7q22-qter (which means 7q22 to theterminus), and the genes for the red and green pigments are on the X chromosome at Xq28 separated by less than 5cM (roughly 5 Mb of DNA). Because the red and green pigments arose from the duplication of a single ancestralpigment gene and are still 96 percent identical in amino acid sequence, the genes are similar enough that they canpair and undergo unequal crossing-over.
The process of unequal crossing-over is the genetic basis of red-greencolor blindness.Almost everyone is familiar with red-green color blindness; it is one of the most common inherited conditions inhuman beings. Approximately 5 percent of males have some form of red-green color blindness. The preponderanceof affected males immediately suggests X-linked inheritance, which is confirmed by pedigree studies (Section 3.4).Affected males have normal sons and carrier daughters, and the carrier daughters have 50 percent affected sons and50 percent carrier daughters.Actually, there are several distinct varieties of red-green color blindness. Defects in red vision go by the names ofprotanopia, an inability to perceive red, and protanomaly, an impaired ability to perceive red.
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