Chapter Introduction

Large-Scale Chromosomal Changes

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Large-Scale

Chromosomal

Changes

CHAPTER

17

LEARNING OUTCOMES

After completing this chapter, you will be able to

  • Distinguish between the major types of chromosomal mutations at the cytological level.

  • Draw meiotic pairing configurations for all the major chromosomal mutations.

  • Predict progeny ratios of specific autopolyploids heterozygous for one or more genes.*

  • Design crosses to synthesize an allotetraploid.

  • Predict the outcome of first and second division meiotic nondisjunction.*

  • Identify an aneuploid using genetic criteria.*

  • Predict ratios in progeny of specific aneuploids.*

  • Distinguish between the main human aneuploid types.

  • In progeny analysis, diagnose the presence of one of the major types of chromosome rearrangements (translocations, inversions, deletions, duplications).*

  • In a cross involving a known specific rearrangement, predict the inheritance of genes linked and unlinked to the rearrangement.*

  • Predict patterns of expression of genes potentially affected by position-effect variegation.

*In the case of chromosomal mutations, progeny analysis involves analyzing patterns of one or more of the following: sterility, lethality, and phenotypic proportions of genes heterozygous in the crosses.

A reciprocal translocation demonstrated by chromosome painting. A suspension of chromosomes from many cells is passed through an electronic device that sorts the chromosomes by size. DNA is extracted from individual chromosomes, denatured, bound to one of several fluorescent dyes, and then added to partly denatured chromosomes on a slide. The fluorescent DNA “finds” its own chromosome and binds along its length by base complementarity, thus “painting” it. In this example, a red and a green dye have been used to paint different chromosomes. The figure shows unpainted (above) and painted (below) preparations. The painted preparation shows one normal green chromosome, one normal red, and two that have exchanged segments.
[Addenbrookes Hospital/Science Source.]

OUTLINE

17.1 Changes in chromosome number

17.2 Changes in chromosome structure

17.3 Overall incidence of human chromosome mutations

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Figure 17-1: Child with Down syndrome
Figure 17-1: Down syndrome results from having an extra copy of chromosome 21.
[Terry Harris/Rex Features/Associated Press.]

A young couple is planning to have children. The husband knows that his grandmother had a child with Down syndrome by a second marriage. Down syndrome is a set of physical and mental disorders caused by the presence of an extra chromosome 21 (Figure 17-1). No records of the birth, which occurred early in the twentieth century, are available, but the couple knows of no other cases of Down syndrome in their families.

The couple has heard that Down syndrome results from a rare chance mistake in egg production and therefore decide that they stand only a low chance of having such a child. They decide to have children. Their first child is unaffected, but the next conception aborts spontaneously (a miscarriage), and their second child is born with Down syndrome. Was their having a Down syndrome child a coincidence, or did a connection between the genetic makeup of the child’s father and that of his grandmother lead to their both having Down syndrome children? Was the spontaneous abortion significant? What tests might be necessary to investigate this situation? The analysis of such questions is the topic of this chapter.

We have seen throughout the book that gene mutations are an important source of change in the genomic sequence. However, the genome can also be remodeled on a larger scale by alterations to chromosome structure or by changes in the number of copies of chromosomes in a cell. These large-scale variations are termed chromosome mutations to distinguish them from gene mutations. Broadly speaking, gene mutations are defined as changes that take place within a gene, whereas chromosome mutations are changes in a chromosome region encompassing multiple genes. Gene mutations are never detectable microscopically; a chromosome bearing a gene mutation looks the same under the microscope as one carrying the wild-type allele. In contrast, many chromosome mutations can be detected by microscopy, by genetic or molecular analysis, or by a combination of all techniques. Chromosome mutations have been best characterized in eukaryotes, and all the examples in this chapter are from that group.

Chromosome mutations are important from several biological perspectives. First, they can be sources of insight into how genes act in concert on a genomic scale. Second, they reveal several important features of meiosis and chromosome architecture. Third, they constitute useful tools for experimental genomic manipulation. Fourth, they are sources of insight into evolutionary processes. Fifth, chromosomal mutations are regularly found in humans, and some of these mutations cause genetic disease.

Many chromosome mutations cause abnormalities in cell and organismal function. Most of these abnormalities stem from changes in gene number or gene position. In some cases, a chromosome mutation results from chromosome breakage. If the break occurs within a gene, the result is functional disruption of that gene.

For our purposes, we will divide chromosome mutations into two groups: changes in chromosome number and changes in chromosome structure. These two groups represent two fundamentally different kinds of events. Changes in chromosome number are not associated with structural alterations of any of the DNA molecules of the cell. Rather, it is the number of these DNA molecules that is changed, and this change in number is the basis of their genetic effects. Changes in chromosome structure, on the other hand, result in novel sequence arrangements within one or more DNA double helices. These two types of chromosome mutations are illustrated in Figure 17-2, which is a summary of the topics of this chapter. We begin by exploring the nature and consequences of changes in chromosome number.

Figure 17-2: Types of chromosome mutations
Figure 17-2: The illustration is divided into three colored regions to depict the main types of chromosome mutations that can occur: the loss, gain, or relocation of entire chromosomes or chromosome segments. The wild-type chromosome is shown in the center.