Chapter 8: Variation in Chromosome Structure and Number

Chapter 8: Variation in Chromosome Structure and Number Student Learning Objectives Upon completion of this chapter you should be able to: 1. Know the principles and terminology associated with variations in chromosome structure. 2. Know the principles and terminology associated with variations in chromosome number. 3. Recognize the effects of chromosomal changes on the phenotype of the organism and/or its offspring. 4. Understand the processes of mitotic nondisjunction, meiotic nondisjunction, and chromosome loss. 5. Understand the experimental techniques that can be used to produce changes in chromosome number. 8.1 Microscopic Examination of Eukaryotic Chromosomes In earlier chapters we dealt with the topic of allelic variation. In this chapter we focus on chromosome variation, which comes in two main types: variations in structure and variations in number. These larger alterations may affect the expression of many genes simultaneously, thereby influencing phenotypes. The first section introduces us to scientists called cytogeneticists, who study the structure and function of chromosomes. To analyze the chromosomal composition of a species, the chromosomes in actively dividing cells are examined microscopically. Cytogeneticists have various ways to classify and identify chromosomes. The three most commonly used features are: 1) size; 2) centromere location; and 3) banding patterns (Refer to Figure 8.1). Genetic variation Allelic variation Cytogeneticist Chromosome types Metacentric Submetacentric Acrocentric Telocentric Metacentric Karyotype G Bands Features of normal chromosomes (Figure 8.1) 103

Exercises and Problems For questions 1 to 4, match the chromosome type to its correct description. a. submetacentric b. telocentric c. metacentric d. acrocentric 1. The centromere is at one end 2. The centromere is closer to the end than to the middle. 3. The centromere is near the middle. 4. The centromere is slightly off center. 8.2 Changes in Chromosome Structure: An Variations in chromosome structure can occur in many ways. In some cases, the total amount of genetic material within a single chromosome can be increased or decreased significantly. In other cases, the genetic material in one or more chromosomes may be rearranged without affecting the total amount of material. This section provides an introduction to the four main types of chromosomal structural changes: deletion, duplication, inversion, and translocation. Deletion Deficiency Duplication Inversion Translocation Simple translocation Reciprocal translocation Types of changes in chromosome structure (Figure 8.2) Exercises and Problems For questions 1 to 4, complete the sentence with the most appropriate term(s): 1. A(n) involves a change in direction of the DNA material along a single chromosome. 2. A(n) occurs when a segment of a chromosome is missing. 3. In a(n) two different types of chromosomes exchange pieces. 4. In a(n) a single piece of chromosome is attached to another chromosome. 104

8.3 Deletions and Duplications In this and the next section we will take a closer look at changes in the structure of a single chromosome (or sometimes two), and how this may influence the expression of genes and the phenotype of the organism. Typically, student difficulties with this chapter rest primarily in the terminology associated with each form of variation. One of the best mechanisms of studying this material is to draw your own examples of each form of variation, noticing the loss/gain/change of genetic material on the chromosomes. The first two forms of chromosome variation, deletions and duplications, involve changes in the total amount of genetic material within a chromosome. In general, deletions are more harmful than duplications. Some deletions are associated with human genetic disorders such as cri-du-chat syndrome (Figure 8.4). Note that deletions and duplications may occur simultaneously due to a misaligned crossing over event (Figure 8.5). While the duplication may have an effect on the phenotype of the organism, it can also have important evolutionary consequences. Gene duplications may form gene families, such as the globin gene family in humans (Figure 8.7). Gene families provide a species with a set of closely related proteins that have slight variations in function. Other consequences of duplications include copy number variations. These refer to a type of structural variation in which a segment of DNA that is 1 Kilobasepair or more in length exhibits copy number differences in members of the same species (Figure 8.8). Deletion Terminal deletion Interstitial deletion Nonallelic homologous recombination Duplication Gene duplication Gene family Homologous genes Paralogs Repetitive sequences Copy number variations Segmental duplication Production of terminal and interstitial deletions (Figure 8.3) Nonallelic homologous recombination (Figure 8.5) Gene duplication and the evolution of paralogs (Figure 8.6) Exercises and Problems For questions 1 to 4, complete the sentence with the most appropriate term(s): 1. A deletion that occurs in the middle of a chromosome is termed. 2. CNV, or, are fairly common structural variations in members of the same species. 3. Homologous genes in a single species are called and constitute a gene family. 4. The globin gene family includes genes for the proteins and. 104

For questions 5 to 11, use the following key: a. statement applies to deletions only b. statement applies to duplications only c. statement applies to both deletions and duplications d. statement applies to neither deletions nor duplications 5. Responsible for the formation of gene families 6. The cause of Angelman syndrome and Prader-Willi syndrome 7. Includes pericentric and paracentric types 8. The cause of cri-du-chat syndrome 9. The cause of Charcot-Marie-Tooth disease 10. May arise from nonallelic homologous recombination 11. Alters the total amount of genetic material 8.4 Inversions and Translocations This section examines inversions and translocations, which are chromosomal rearrangements. Both tend to be more difficult to visualize than the duplication/deletions previously presented. However, the text and figures do a good job at elucidating these complex chromosomal changes. Inversions can be divided into two types, pericentric and paracentric, based on the presence or absence of the centromere in the inverted segment (Figure 8.9). Translocations may be caused by different mechanisms, including chromosome breakage and subsequent repair, and nonhomologous crossing over (Figure 8.11). A particular type of translocation is termed Robertsonian. It involves an exchange between a short arm and a long arm of two acrocentric chromosomes (Figure 8.12). Familial Down syndrome is due to such an event (See Figure 8.13). Two other key figures you need to focus on are 8.10 and 8.14. Notice how the chromosomes align during meiosis. Pay special attention to the effects of these forms of variation on the production of gametes. Both of these may result in reduced fertility for an organism due to the loss of gametes because of chromosomal abnormalities. Inversion Pericentric inversion Paracentric inversion Position effect Inversion heterozygote Inversion loop Dicentric chromosome Dicentric bridge Acentric fragment Telomeres Translocation Simple translocation Unbalanced translocation Reciprocal translocation Balanced translocation Robertsonian translocation Translocation cross Semisterility 104

Types of inversions (Figure 8.9) Inversion loops (Figure 8.10) Causes of translocations (Figure 8.11) Transmission of familial Down syndrome (Figure 8.13) Translocation crosses (Figure 8.14) Exercises and Problems For questions 1 to 5, complete the sentence with the most appropriate term(s): 1. A piece of chromosome without a centromere is termed an. 2. translocations are reciprocal translocations that do not alter the total amount of genetic material. 3. In a inversion, the centromere lies outside the inverted region of a chromosome. 4. Familial Down syndrome is caused by a between chromosomes 14 and 21. 5. A refers to a change in phenotype that occurs when the location of a genes changes from one chromosomal site to another. For questions 6 to 10, assume that two non-homologous chromosomes have the following combination of genes: -----------o-------------- ------------o--------------- A B C D E F G Q R S T U V For each combination indicated below, state the form of structural variation (duplication, deletion, inversion, and translocation) that would have to occur to produce the sequence shown. The ----o---- indicates the location of the centromere. Note that some answers may require more than one process. 6. ------------- o ---------------- A B C D G F E 7. ------------- o ---------------- ------------- o ---------------- A B C D U V Q R S T E F G 8. ------------- o ---------------- A B C D F G 9. ------------- o ---------------- ------------- o ---------------- A B C D E Q R S T U V G F 10. --------------- o ---------------- A B A B C D E F G 106

For questions 11 to 16, use the following key: a. statement applies to inversions only b. statement applies to translocations only c. statement applies to both inversions and translocations d. statement applies to neither inversions nor translocations 11. In some cases, the chromosomes form a cross pattern during meiotic pairing 12. Can result in the formation of a chromosome with a dicentric bridge 13. Usually caused by modifications to the telomere of the chromosome 14. Causes homologous chromosomes to form a loop during meiotic pairing 15. Caused by a crossover between homologous chromosomes 16. Involves a chromosomal rearrangement 8.5 Changes in Chromosome Number: An As we saw in the three previous sections, chromosome structure can be altered in a variety of ways. Likewise, the total number of chromosomes can vary. This section introduces these numerical changes, which can be divided into two main groups: 1) Euploidy, or variations in the number of sets of chromosomes; and 2) aneuploidy, which is variation in the number of particular chromosomes within a set. Refer to Figure 8.15 for a good overview. Euploidy Polyploid Triploid Tetraploid Aneuploidy Trisomic Monosomic Types of variations in chromosome number (Figure 8.15) Exercises and Problems In the garden pea, Pisum sativum, 2n = 14. How many chromosomes would each of the following have? 1. A diploid cell 2. A triploid cell 3. A tetraploid cell 4. A trisomic cell 5. A monosomic cell 107

8.6 Variation in the Number of Chromosomes Within A Set: Aneuploidy Changes in chromosome number also have an effect on gene expression and the phenotype of the organism. Once again, the most common problems with the next two sections occurs in the terminology. However, the terminology for variations in chromosome number is actually easy to understand if you take the time to examine the term for patterns. Before proceeding into this section, study the material in Figure 8.15 carefully. Aneuploidy involves an alteration in a number that is not an exact multiple of a chromosome set. These chromosome changes may be represented algebraically. For a diploid organism (2n), examples of aneuploidy include trisomy (2n + 1) and monosomy (2n 1). One of the more important concepts of this section is how these conditions relate to gene expression. Previously in the text the concept of proteins being responsible for phenotypes was introduced. We have observed how many organisms are very careful to regulate levels of gene expression when the chromosome number is not the same in the sexes. Therefore, any change in chromosome number should also have an effect on the phenotype. This is basically due to an imbalance in gene products (Refer to Figure 8.16). The section also takes a look at the various aneuploid conditions in humans (Table 18.1). It focuses on Down syndrome, which is the most famous of these conditions. Note how the incidence of Down syndrome births increases with maternal age (Figure 8.17). Nondisjunction Imbalance of gene products (Figure 8.16) Aneuploid conditions in humans (pages 175-176, Table 8.1) The incidence of Down syndrome births according to the age of the mother (Figure 8.17) Exercises and Problems For questions 1 to 6, complete the sentence with the most appropriate term(s): 1. In humans, a single set of chromosomes contains about to different genes. 2. refers to the failure of chromosomes to separate normally during cell division. 3. An individual with triple X syndrome has a total of chromosomes in each cell. 4. Klinefelter syndrome only affects. 5. syndrome may also be termed monosomy X. 6. Incidence of Down syndrome increases with the mom s age, because as the woman ages, her primary oocytes have been arrested in of meiosis for a progressively longer period of time. 108

For each of the following conditions in humans, indicate whether the condition is due to a change in the number of autosomal or sex chromosomes, and the genotype of the individual. 7. Jacobs Syndrome 8. Klinefelter Syndrome 9. Turner Syndrome 10. Down Syndrome 11. Patau Syndrome 12. Edwards Syndrome 8.7 Variation in the Number of Sets of Chromosomes Euploidy involves changes in the number of sets of chromosomes. This phenomenon is rare in animals. Indeed, it is not tolerated at all in mammals. However, there are examples of naturally occurring variations in euploidy. These include the haplodiploidy system of bees and ants, where males are haploid and females are diploid. Note that some tissues in an animal may exhibit polyploidy. An example is the polytene chromosomes found in the salivary cells of Drosophila (Refer to Figure 8.19). Polyploidy is common in plants, and has found many advantages in agriculture. Many of the foods and grains we eat are produced from polyploidy plants. These tend to be larger and more robust than their diploid counterparts (See Figure 8.20b). Also note that polyploid plants having an odd number of chromosome sets usually cannot reproduce sexually. This is due to the unequal separation of homologous chromosomes during anaphase I of meiosis (Figure 8.21). Haplodiploid Endopolyploidy Polytene chromosomes Chromocenter Polytene chromosomes in Drosophila (Figure 8.19) Examples of polyploid plants (Figure 8.20) Schematic representation of anaphase I of meiosis in a triploid organism containing three sets of four chromosomes (Figure 8.21) 109

Exercises and Problems Complete the following sentences with the most appropriate word or phrase: Variations in euploidy occur naturally in a few animal species. These include bees, which are an example of a haplodiploid species. Male bees, also called drones, are (1). They are produced from (2) eggs. In contrast, female bees are produced from (3) eggs and are thus (4). Variations in euploidy can also occur in certain tissues within an animal. The occurrence of polyploid tissues or cells in an organism that is otherwise diploid is known as (5). For example, human (6) cells contain nuclei that can be triploid, tetraploid, and even octoploid. An unusual example occurs in (7) and other insects. In the salivary glands of these animals, several rounds of repeated replication without cellular division produce a bundle of sister chromatids that lie side by side. This bundle is called a (8). The central point where the chromosomes aggregate is called the (9). For each of the following, indicate the algebraic formula for the chromosome number in the organism. 10. Tetraploid 11. Octaploid 12. Trisomic 13. Hexaploid 14. Monosomic 15. Haploid 8.8 Mechanisms that Produce Variation in Chromosome Number The last section of this chapter examines the mechanisms by which variations in chromosome number may occur. These mechanisms can be divided into two general classes: those that naturally occur as a result of cell division, and those that are used by researchers to artificially alter the chromosome number. You should recognize that regardless of which occurs, the outcome is the same since the result is a cell that produces abnormal levels of protein. Naturally, variations in chromosome number may occur as a result of nondisjunction. While this usually occurs during meiotic cell division (Figure 8.22), it may also happen during mitosis (Figure 8.23). Notice the difference between these two forms. This section of the chapter also presents the concept of alloploidy, in which an organism contains chromosomes from two different species. This introduces a whole new level to the terminology from the previous section, since an organism may have multiple sets of chromosomes, but not from the same species. One of the more interesting aspects of chance in chromosome number is the influence of alloploidy on sterility. The final part of this section takes a look at an experimental procedure used to promote polyploidy. These include the use of the drug colchicine, which causes complete nondisjunction (Refer to Figure 8.28). 110

Nondisjunction Mitotic nondisjunction Meiotic nondisjunction Complete nondisjunction Mosaicism Bilateral gynandromorphy Autopolyploidy Alloploidy Homeologous chromosomes Allodiploidy Allopolyploidy Allotetraploidy Nondisjuntion during meiosis (Figure 8.22) Nondisjunction and chromosome loss during mitosis (Figure 8.23) A comparison of autopolyploidy, alloploidy, and allopolyploidy (Figure 8.25) Exercises and Problems For questions 1 to 6, use the following key: a. statement applies to mitotic nondisjunction only b. statement applies to meiotic nondisjunction only c. statement applies to both forms of nondisjunction d. statement applies to neither form of nondisjunction 1. Results in a mosaic pattern of chromosome number in the organism. 2. May result in an organism called a bilateral gynandromorph. 3. Involves movement of two sister chromatids to the same pole. 4. Produces a normal cell and a monosomic cell. 5. By complete nondisjunction, this may produce a gamete without chromosomes. 6. Occurs in the somatic cells of the organism. For questions 7 to 11, match the term with its correct definition. 7. Autopolyploidy 8. Allodiploid 9. Allotetraploid 10. Homeologous 11. Alloploid a. An organism containing chromosome sets from more than one species. b. An organism that has two complete sets of chromosomes from two different species. c. An increase in the number of chromosome sets in a single species. d. Evolutionarily related chromosomes from different species. e. An organism that has one complete chromosome set from two different species. 111

Chapter Quiz 1. Which of the following represents an organism with two complete sets of chromosomes from two different species? a. autotetraploid b. allotetraploid c. allodiploid d. tetrasomy e. none of the above 2. Which of the following is NOT an example of an autosomal aneuploidy? a. Down syndrome b. Turner syndrome c. Edwards syndrome d. Patau syndrome e. Choose this answer if all of the above are autosomal aneuploidies 3. A chromosome has the gene sequence A B C D E F G H I (where = the centromere) Which of the following is an example of a pericentric inversion? a. A D C B E F G H I b. A B C D E H G F I c. A B F G H I d. A B C D E F G H I F G H I e. A B C D G F E H I 4. Which of the following indicates the chromosome number of an individual with non-familial Down syndrome? a. 2n 1 b. 3n c. 2n + 1 d. n + 2 5. Cri-du-chat syndrome is a result of a(n). a. inversion b. translocation c. deletion d. duplication 6. Liver cells in humans exhibit which of the following? a. alloploidy b. endopolyploidy c. monoploidy d. aneuploidy 7. A bilateral gynandromorph is the result of. a. mitotic nondisjunction b. meiotic nondisjunction c. chromosome loss d. reciprocal translocation e. paracentric inversion 109

8. Which of the following individuals will have the MOST trouble in producing functional gametes during meiosis? a. triploid with 30 total chromosomes b. tetraploid with 48 total chromosomes c. tetraploid with 60 total chromosomes d. diploid with 46 total chromosomes e. diploid with 8 total chromosomes 9. The loss of the telomere on a chromosome tends to favor which of the following? a. inversions b. deletions c. duplications d. translocations e. nondisjunction 10. The house mouse Mus musculus has a diploid chromosome number of 40. Suppose that the first meiotic division of a germ cell is normal, but a single chromosome in one of the two daughter cells undergoes non-disjunction in meiosis II. How many chromosomes would be present in each of the four gametes that result from that meiosis? a. 12, 12, 8, 8 b. 10, 10, 12, 8 c. 22, 20, 18, 16 d. 21, 21, 19, 19 e. 20, 20, 21, 19 Answer Key for Study Guide Questions This answer key provides the answers to the exercises and chapter quiz for this chapter. Answers in parentheses ( ) represent possible alternate answers to a problem, while answers marked with an asterisk (*) indicate that the response to the question may vary. 8.1 1. b 2. d 3. c 4. a 8.2 1. inversion 2. deletion (deficiency) 3. reciprocal translocation 4. simple translocation 8.3 1. interstitial 2. copy number variations 3. paralogs 4. hemoglobin and myoglobin 5. b 6. a 7. d 8. a 9. b 10. c 11. c 110

8.4 1. acentric fragment 2. balanced 3. paracentric 4. Robertsonian translocation 5. position effect 6. paracentric inversion 7. reciprocal translocation 8. interstitial deficiency 9. simple translocation and paracentric inversion of F G 10. duplication 11. b 12. a 13. b 14. a 15. d 16. c 8.5 1. 14 2. 21 3. 28 8.6 1. 20,000 to 25,000 2. nondisjunction 3. 47 4. males 5. Turner 6. prophase I 7. sex, XYY 8.7 1. haploid 2. unfertilized 3. fertilized 4. diploid 5. endopolyploidy 6. liver 7. Drosophila 8. polytene chromosome 8.8 1. a 2. a 3. c 4. d 5. b 6. a 7. c 8. e 4. 15 5. 13 8. sex, XXY 9. sex, XO 10. autosomal, trisomy 21 11. autosomal, trisomy 13 12. autosomal, trisomy 18 9. chromocenter 10. 4n 11. 8n 12. 2n + 1 13. 6n 14. 2n - 1 15. n 9. b 10. d 11. a Quiz 1. b 2. b 3. b 4. c 5. c 6. b 7. a 8. a 9. d 10. e 109