Chapter 5 Chromosomes PDF

Chromosomes J CHAPTER OUTLINE 5.1 Bacterial Chromatin The precise nature of the interaction between H1 and the core particle is not known. B...

Chromosomes J CHAPTER OUTLINE 5.1 Bacterial Chromatin The precise nature of the interaction between H1 and the core particle is not known. Bacterial DNA is located in the nucleoid. We do not know how nucleosomes are arranged in chromatin. 0.2 Introduction to Eukaryotic Chromatin Condensins and topoisomerase II help to stabilize condensed chromosomes. Eukaryotic chromatin is visible under the light microscope during The scaffold model was proposed to explain higher order certain stages of the cell cycle. chromatin structure. 5.3 Mitosis 5] The Centromere The animal cell life cycle alternates between interphase The centromere is the site of microtubule attachment. and mitosis. Mitosis allows cells to maintain the chromosome number 0.8 The Telomere after cell division. The telomere, which is present at either end of a chromosome, is needed for stability. 54 Meiosis BOX 5.1: CLINICAL APPLICATION Karyotype anc Meiosis reduces the chromosome number in half. 5.5 Karyotype Chromosome sites are specified according to nomenclature conventions. A karyotype shows an individual cell's metaphase chromosomes arranged in pairs and sorted by size. Fluorescent in situ hybridization (FISH) provides a great deal of information about chromosomes. 5.6 The Nucleosome Five major histone classes interact with DNA in eukaryotic chromatin. The first level of chromatin organization is the nucleosome. X-ray crystallography reveals the atomic structure of nucleosome core particles. Image courtesy of Jane Ades/NHGRI.  NA molecules are extremely long in comparison with the size of living cells and so must be compacted to fit the available space inside a cell. Specific proteins interact with DNA, leading to the formation of a condensed nucleoprotein complex called chromatin. Until the mid-1970s biologists’ view of chromatin was influenced by the belief that all life on Earth belonged to one of two primary lineages, the eukaryotes (animals, plants, and fungi, which have a defined nucleus) and the prokary- otes (all remaining microscopic organisms that lack a defined cell nucleus). Based on this classification scheme and what was then known about chromatin structure, it seemed likely that prokary- otes would have one type of chromatin structure and eukaryotes would have another. Then in 1977 Carl Woese proposed the pro- karyotes actually contain two types of organisms, the bacteria and the archaea. Once the existence of the three domains of life was established, it seemed possible that each domain would have a characteristic chromatin structure. Experimental studies, however, do not support this possibility. As the following examples illustrate, differences in the chromatin structures of organisms within a single domain are nearly as great as those among organisms belonging to different domains: 1. Variations in chromatin structure exist in bacteria. DNA molecules in most bacterial species that have been studied to date have circular structures like those of the DNA molecules in Escherichia coli. DNA molecules in some bacteria, how- ever, such as Agrobacterium tumefaciens (a species that infects plants) and Streptomyces species, are linear duplexes and in this respect resemble eukaryotic DNA. 2. Most, but not all, eukaryotes contain chromatin formed by interactions between linear duplex DNA and a family of basic proteins called histones. However, dinoflagellates, a very large and diverse group of eukaryotic algae, lack histones completely. 3. The archaea exhibit, if anything, even greater variations in | chromatin structure than do organisms belonging to the other two domains. Some archaea appear to form nucleoprotein complexes that resemble those present in eukaryotes, whereas others seem to form nucleoprotein complexes that resemble those in bacteria. As this brief overview shows, it is not possible to examine the chromatin structure from a single kind of organism and expect the information will apply to all organisms within the same domain. We can certainly obtain valuable information about chromatin structure in related organisms, however, and hope this informa- tion will eventually permit us to obtain a coherent picture. With this thought in mind, we begin by examining bacterial chromatin structure and then examine chromatin structure in higher animals and plants. CHAPTER 5 CHROMOSOMES  | Bacterial Chromatin Bacterial DNA is located in the nucleoid. E. coli DNA, which appears as a closed covalent circle with a total length of about 1,600 jm, must fit into a cylindrical cell with a diam- eter of about 0.5 wm and a length of about 1 wm. The intracellular DNA 1s therefore about 1,000-fold more compact than the free DNA. Specific proteins interact with the bacterial DNA to form a highly condensed nucleoprotein complex called the nucleoid that occupies about a quarter of the cell’s volume (FIGURE 5.1). Bacterial chromatin can be released from the cell by a gentle cell lysis (disruption) technique that avoids DNA breakage or protein denaturation. The released DNA contains a fixed amount of protein and a variable amount of RNA. Most of the RNA is probably nascent RNA (RNA caught in the process of being synthesized) rather than an integral part of the bacterial chromatin. An electron micrograph of released E. coli chromatin reveals mul- FIGURE 5.1 An electron micrograph of a thin tiple loops emerging from a central region, with some loops supercoiled section of Escherichia coli. The nucleoid is the and others relaxed (FIGURE 5.2). Relaxed loops were probably formed light region. (Photo courtesy of the Molecular as a result of a nick introduced into supercoiled loops by a cellular and Cell Biology Instructional Laboratory Program, University of California, Berkeley.) relaxed region OS supercoiled region FIGURE 5.2 Electron micrograph of chromatin released from an E. coli cell after gentle cell disruption. Multiple loops can be seen emerging from a central region with some loops supercoiled and others relaxed. (Photo courtesy of Bruno Zimm and Ruth Kavenoff. Used with permission of Louis Zimm.) 5.1 Bacterial Chromatin 18  DNase during the isolation procedure. The fact that supercoiled and relaxed loops are both present indicates that each loop is somehow insulated from the others. Further support for loop insulation comes from studies in which released E. coli chromatin was observed at different times after add- ing trace quantities of DNase. If a supercoiled DNA molecule receives one nick, the strain of underwinding is immediately removed by free rotation around the opposing sugar-phosphate bond, and all super- coiling is lost. Because a nicked circle is much less compact than a supercoiled molecule of the same molecular mass, the nicked circle sediments much more slowly. One nick thus causes an abrupt decrease (by about 30%) in the sedimentation value. The sedimentation value decreases continuously, however, when DNase introduces one nick at a time into released E. coli chromatin. That is, the structure does not change in an all-or-none fashion but proceeds through a large number of intermediate states. This finding indicates that free rota- tion of the entire DNA molecule does not occur when a single nick is introduced. Electron microscopy studies confirm that as nuclease treatment continues, the number of nonsupercoiled loops increases. A model of E. coli chromatin deduced from sedimentation and electron microscopy studies is shown in FIGURE 5.3. According to this model the bacterial DNA is arranged in supercoiled loops that are fastened to a central protein matrix so each supercoiled loop is topologically independent of all the others. A nick that causes one supercoiled loop to relax would therefore have no effect on other supercoiled loops. The E. coli chromosome is estimated to have about 400 such loops, each with an average length of about 10 to 20 kilobase pairs. Biochemical and genetic studies show that supercoiled loops are dynamic structures, which change during cell growth and division. This change allows the entire chromosome to be accessible to the transcription machinery and other enzymes throughout the cell cycle. Although supercoiling makes an important contribution to bacterial DNA compaction, it is not the only factor. Macromolecular crowding and DNA-binding proteins also contribute to DNA compaction. High Folded supercoiled Nick allows this bacterial chromosome loop to become relaxed 1 additional nick Protein core FIGURE 5.3 Model of bacterial chromosome folding. The E. coli chromosome has about 400 negatively supercoiled loops attached to a central protein matrix. Each loop (average length of about 10 kilobase pair) is topologically independent of the others. CHAPTER 5 CHROMOSOMES intracellular soluble macromolecule concentration limits the avail- able aqueous volume, forcing the DNA to become more compact. Crowding also favors interactions between DNA and the proteins that bind to it. Some of the proteins that help to determine bacterial chromatin architecture are as follows: 1. The MukB protein. The MukB protein helps to organize and compact DNA. 2. H-NS (histone-like nucleoid structuring) protein. The active form of H-NS appears to be a homodimer (or perhaps an oligomer), which form bridges across DNA segments. Little is known about the way that the protein bridges DNA. 3. DNA bending proteins. Three nucleoid associated proteins bend DNA. Two of these, IHF (integration host factor) and HU (heat unstable) protein are closely related heterodimers. The third nucleoid associated protein that bends DNA, FIS (factor for inversion stimulation), is a homodimer. bh? Introduction to Eukaryotic Chromatin Eukaryotic chromatin is visible under the light microscope during certain stages of the cell cycle. Eukaryotic chromatin can be seen as highly condensed structures called chromosomes under a light microscope during certain stages of cell division. As biologists carefully examined chromosomes in many different kinds of cells from various higher animals, two important conclusions emerged. First, reproductive or germ cells have a charac- teristic number of chromosomes (n). This number, called the haploid number, is 3, 4, 23, and 30 for germ cells from the mosquito, fruit fly, human, and cattle, respectively. Second, nonreproductive or somatic cells, such as those from lung, kidney, and brain, contain two versions of each chromosome (one from each parent) called homologs. Because somatic cells have twice the number of chromosomes as germ cells they are said to be diploid (2n). 53 Mitosis The animal cell life cycle alternates between interphase and mitosis. Mitosis is a type of nuclear division that ensures the two daughter cells resulting from cell division each has the same number of chromosomes as the parent cell. A eukaryotic cell spends only a part of its life cycle (the time between its formation by parent cell division and its own divi- sion to form two daughter cells) in mitosis. The remainder of the time, often approaching 90% of its life cycle, is spent in interphase, a stage 5.3 Mitosis  Heterochromatin Nucleolus Euchromatin Nuclear membrane FIGURE 5.4 Electron micrograph of a liver cell nucleus. (© Phototake, Inc./ Alamy Images.) during which DNA, RNA, protein, and other biological molecules are synthesized. Two forms of chromatin, a less condensed form called euchromatin and a more condensed form called heterochromatin, are present in the eukaryotic nucleus during interphase (FIGURE 5.4). Euchromatin, the predominant form, is actively transcribed during interphase. In contrast, heterochromatin, which tends to be located near the nuclear membrane, is not actively transcribed. Nearly all regions of the human genome that remain to be sequenced are in the heterochromatin. DNA replication and histone synthesis occur during only a part of interphase, the DNA synthetic phase or $ phase. The S phase is bracketed by two gap phases, G, and G,, so that the stages in the life cycle are in the order G; — S > G, > M (FiGuRe 5.5). The timing of | S, G, and M tend to be relatively uniform for a given type of somatic cell. However, time spent in G,, a period of active protein, lipid, and carbohydrate synthesis, is quite variable. Some eukaryotic cells spend almost their entire life cycle in G. Mitosis allows cells to maintain the chromosome number after cell division. Even though mitosis is a continuous process, it is usually divided into four stages for convenience. Chromosomal changes during these four stages, which occur in the order prophase + metaphase > anaphase > telophase, are depicted in FIGURE 5.6 and summarized below. 1. Prophase. Chromatin, which was replicated during the $ phase of interphase, condenses to form visibly distinct chromosomes. Each chromosome is divided along its long axis into two identical CHAPTER 5 CHROMOSOMES  M Mitosis Gy (gap 1) Pre-DNA synthesis Gp (gap 2) Post-DNA synthesis DNA synthesis FIGURE 5.5 The cell cycle of a typical mammalian cell growing in tissue culture with a generation time of 24 hours. subunits called sister chromatids that are held together by a pro- tein called cohesin. Cohesin is enriched about threefold in a 20- to 50-kb domain flanking a specific chromosomal region known as the centromere (see below), relative to its concentration on chromosome arms. As prophase ends the nuclear region involved in ribosomal RNA synthesis, called the nucleolus, disappears and the nuclear membrane disassembles to form membrane vesicles. A mitotic spindle, consisting of fiber-like bundles of protein molecules called microtubules, starts to form. 2. Metaphase. The assembly of the mitotic spindle is completed, and the spindle moves to the region previously occupied by the nucleus. Several spindle fibers attach to each chromosome in a region of the centromere called the kinetochore (see below). Once attachment is complete the chromosomes move toward the center of the cell until the kinetochores lie in an imaginary plane equidistant from the two spindle poles. Each chromo- some must be attached to both poles of the spindle, and the chromosomes must be properly aligned along the imaginary plane equidistant from the spindle poles for mitosis to proceed to the next stage. We can learn a great deal by examining chromosomes during the metaphase (see below). 3. Anaphase. Cohesin is cleaved, and cohesion between sister chromatids is dissolved. The two sister chromatids (now con- sidered to be separate chromosomes) move toward opposite spindle poles so that an equal number of identical chromosomes are located at either end of the spindle as anaphase comes to a close. The number of chromosomes in each group is the same as that present in the cell nucleus at the start of interphase. 4. Telophase. The spindle disappears, nuclear membranes form around the two groups of chromosomes, and nucleoli re-form. Chromosomes become less and less condensed until they can no longer be seen with a light microscope. The cells divide to produce two identical daughter cells. 5.3 Mitosis 1m  Nuclear envelope Chromatid Centromere Nucleolus N= Interphase Late prophase Spindle Metaphase MITOSIS FIGURE 5.6 Chromosome behavior during mitosis in an organism with two pairs of chromosomes (red/rose vs. green/blue). At each stage the smaller inner diagram represents the entire cell, and the larger diagram is an exploded view showing the chromosomes at that stage. 158 CHAPTER 5 CHROMOSOMES | Meiosis Meiosis reduces the chromosome number in half. Eukaryotes use meiosis to reduce the chromosome number in half during sexual reproduction. Unlike mitosis, which maintains the chro- mosome number, meiosis produces gametes (sperm and egg cells) in animals or spores in fungi that have a haploid chromosome number. Meiosis requires two successive nuclear divisions to accomplish this task. The diploid number is reestablished by zygote formation resulting from the union of two haploid cells during sexual reproduction. The first and second meiotic divisions go through prophase, metaphase, anaphase, and telophase stages (FIGURE 5.7). First Meiotic Division 1. Prophase I. Prophase I begins after DNA replication is com- pleted. It is of special interest because chromosome homologs exchange DNA, leading to genetic recombination during this stage. Some of the key changes during prophase I are as follows. The chromatin starts to condense. Beads, called chromomeres, appear at irregular intervals along the length of the chromo- some. The number, size, and arrangement of chromomeres are unique for each kind of chromosome. Homologous chro- mosomes pair. This pairing (synapsis) begins at the chromo- some tips and continues along the chromosome, establishing specific chromomere-chromomere pairing. Fully paired chro- mosomes are called bivalents (indicating that each pair consists of two types of chromosomes) or tetrads (indicating that each homologous pair contains four closely associated chromatids). Paired chromosomes, which are very close together, begin a chromosome exchange process known as crossing over. Con- densation reaches a state in which the sister chromatids in each chromosome become visible. Homologous chromosomes start to separate. Complete separation cannot occur at this stage, however, because the homologous chromosomes are joined by cross-connections called chiasmata (singular, chiasma = cross- piece), which are produced when nonsister chromatids break and reunite during the crossing-over process. Prophase I is divided into the five substages: leptotene, zygotene, pachytene, diplotene, and diakinesis. Figure 5.7 summarizes the important events that take place during each of these substages. 2. Metaphase I. Spindle fibers from one pole make contact with one chromosome in a homologous pair, while spindle fibers from the other pole make contact with the other chromo- some in the pair. Each chromosome moves into the meta- phase plate (the imaginary plane that is equidistant from each spindle pole). 3. Anaphase I. Homologous chromosomes are pulled apart and begin to move to opposite poles. The two members of each homologous pair are separated so that each pole has the hap- loid number of chromosomes. 5.4 Meiosis  Sister chromatids Pairing is complete. become visible. Sister Synapsis, or homologous chromatids chromosome pairing, begins. Chromosomes first become visible. Ee Late pachytene oer Early pachytene Zygotene PROPHASE | (chromosome pairing and condensation; crossing-over) Leptotene Telophase II Centromeres split. FIGURE 5.7 Chromosome behavior during meiosis in an organism with two pairs of homologous chromosomes (red/rose and green/blue). At each stage the small diagram represents the entire cell and the larger diagram is an expanded view of the chromosomes at that stage. CHAPTER 5 CHROMOSOMES Chromosomes become Homologous chromosomes shorter and thicker; repel; they are held chiasmata are prominent. together by chiasmata. Bivalents align on the metaphase plate. Pow Bivalent Homologous chromosomes separate. => Di plotene —. Diakinesis MEIOSIS ,, Metaphase Il Chromosomes align on the metaphase plate. 5.4 Meiosis  4. Telophase I. The single spindle disassembles and two new spindles form in the region that had been occupied by the spindle poles. In some species the nuclear membrane re-forms, whereas in others the chromosomes enter directly into the second meiotic division. There is a seamless transition from telophase I to prophase II. In fact, the transition is so seamless that prophase II is almost nonexistent in many organisms. No chromosomal replication occurs between the first and second meiotic divisions. (a) Second Meiotic Division 1. Prophase II. The chromosomes remaining at the two poles of t P the first meiotic division begin to move to the midpoints of %: 2% ‘% ” the two newly formed spindles. cad Ps e + 2. Metaphase II. Chromosomes align on the metaphase plate. ihe.% a g ® 3. Anaphase II. Cohesins are cleaved, centromeres split, and mY es * Cs 3tad geet ° allel » the chromatids move to opposite poles of the spindle. Each 3 y; cs chromatid is now considered to be a separate chromosome. 4. Telophase II. The chromosomes decondense and nuclear mem- ° o M4 } Ble A * e me. Z i t; > branes form around the four division products to produce four : Cr 2 2 “mee. * & : «es A *. haploid nuclei. i =. &x te t «* * ¥ ser 55 Karyotype (b) Chromosome sites are specified according to ote ef 2 A$. i as ae Wwou of 28 nomenclature conventions. 1 2 3 4 5 Cytogenetics is the scientific discipline concerned with the study of the F A | basa physical appearance of chromosomes. Chromosomes are examined ae 4¢ 3 during the mitotic metaphase, the stage in which each chromosome eee eeeYe es Pe pe if 4 i 6 7 8 9 10 14 12 Xe consists of two highly condensed sister chromatids held together at Cc their centromere by cohesins. The centromere’s position, which may be near the center of the chromosome, off-center, or close to one end, sg 49 OM a ee Of 13 14 15 16 17 18 determines the chromatid arm lengths. The shorter of the two arms is pom QQ I 3 called the p arm (petite arm) and the longer is called the q arm. Investigators attempted to use size and centromere position to 19 20 21 22 Y a -— g ——4 classify human chromosome pairs, but these criteria do not allow unambiguous chromosome identification. With the discovery in the FIGURE 5.8 A karyotype of a normal human late 1960s and early 1970s that certain dyes stain chromosomes to male. Blood cells arrested in metaphase were produce unique and reproducible band patterns, investigators were stained with Giemsa and photographed with a microscope. (a) The chromosomes as seen in able to identify specific chromosome pairs. For example, staining with the cell by microscopy. (b) The chromosomes Giemsa dye produces light and dark transverse bands along the length have been cut out of the photograph and of the chromosome (FIGURE 5.8a). paired with their homologs. Paired homologs Despite the fact that a typical band looks quite narrow when are arranged according to size in groups A, B, viewed with a light microscope, it actually extends over more than a and so forth. The largest homologous pair is in the upper left. X and Y sex chromosomes million base pairs and dozens of genes. Even when different kinds of have not been paired. (Photos courtesy of chromosomes are the same size and have their centromeres located Patricia A. Jacobs, Wessex Regional Genetics in the same place, they can still be distinguished by their unique “bar Laboratory, Salisbury District Hospital.) code” patterns. The bands along a chromosome are part of clearly CHAPTERS CHROMOSOMES delimited regions. Nomenclature conventions for specifying sites in a chromosome, which are illustrated for human chromosome 1 in FIGURE 5.9, are as follows: 1. Each chromosome is assigned a number, with the largest being assigned number 1. 2. The short arm is designated p and the long arm is q. 3. Regions and bands are numbered consecutively from the cen- tromere outward along each chromosome arm. parm 4. Chromosome number, arm, region number, and band number are written in order. A karyotype shows an individual cell's metaphase chromosomes arranged in pairs and sorted by size. A great deal of information can be obtained from digital images of stained chromosomes taken at metaphase. The digital images are cut and pasted with a computer, arranging chromosome pairs by size, shape, and banding pattern to facilitate interpretation. By convention, chro- mosome pairs are arranged in decreasing order of size to produce an arrangement called a karyotype. Figure 5.8b, a human karyotype prepa- ration, reveals the presence of 23 pairs of chromosomes. Twenty-two chromosome pairs, called autosomes, are the same in males and females. The remaining pair, the sex chromosomes, determines the individual’s sex. Male sex chromosomes consist of one X and one Y chromosome, whereas female sex chromosomes consist of the two X chromosomes. A single Y chromosome is sufficient to produce maleness, whereas its absence is required for femaleness. The Y chromosome is smaller than the X chromosome, and the two have different banding patterns. A great deal of information can be obtained by examining karyotype prepara- tions (BOX 5.1 CLINICAL APPLICATION: KARYOTYPE AND DIAGNOSIS). FIGURE 5.9 Human chromosome 1. The Fluorescent in situ hybridization (FISH) provides a great deal of short arm is designated p and the long information about chromosomes. arm q. Regions and bands are numbered consecutively from the centromere outward Classical staining techniques do not provide sufficient sensitivity to along each chromosome arm. (Modified from detect translocations, deletions, or insertions that involve small seg- HYPERLINK http://www.genome.jp.kegg. Used ments within a chromosome. Investigators have taken advantage of with permission of Kanehisa Laboratories lessons learned from molecular biology to devise a very sensitive tech- Bioinformatics Center, Institute for Chemical nique for detecting even very small chromosomal changes in a sample Research, Kyoto University and the Human Genome Center, Institute for Medical Science, fixed to a microscope slide. University of Tokyo.) This technique, called fluorescent in situ hybridization (FISH), takes advantage of the fact that a DNA probe with an attached fluo- rescent dye binds to a specific DNA sequence within a denatured chromosome (FIGURE 5.10). The fluorescent probes can be prepared by nick translation or by the polymerase chain reaction. FISH has a wide variety of applications, which include (1) detecting aneuploidy (a con- dition in which cells have either more or less than the normal diploid number of chromosomes), (2) identifying chromosomal aberrations, and (3) locating genes and other DNA segments on a chromosome. It can also be used to locate DNA segments during interphase when the chromosome is not visible. 5.5 Karyotype  BOX 5.1: CLINICAL APPLICATION Ee] Karyotype and Diagnosis Human karyotype preparations provide important clinical information. Although almost any population of dividing cells can be used to obtain the metaphase cells required for such a preparation, blood, bone marrow, fibroblasts, and amniotic fluid are the most common sources of cells to be analyzed. Isolated cells are incubated with a plantor bacterial protein called a mitogen that binds to receptors on the outer surface of the cell membrane and induces mitosis. After3or 4days of incubation, a drug such as colchicine, which disrupts mitotic spindles, is added to arrest dividing cells in metaphase. The population, now enriched in metaphase cells, is stained and analyzed. Many congenital problems can be identified by chromosomal anomalies. Down syndrome, which occurs in about1 in every 800 births, will serve as an illustra- tive example. Approximately 95% of individuals with Down syndrome have three copies of chromosome 21. Down syndrome is associated with mild to severe forms of mental retardation, which is often accompanied by various medical problems, including epilepsy, heart defects, and a marked susceptibility to respiratory infections. Individuals with Down syndrome also appear to age at an accelerated rate and have a high probability of showing the clinical signs and symptoms of Alzheimer-type dementia after age 40. A condition in which cells have either more or less than the normal diploid number of chromosomes is called aneuploidy. Most cases of simple aneuploidy are caused by errors in chromosomal segregation during meiosis. If pairs of homologous chromosomes do not separate during the first meiotic division or if the centromere joining sister chromatids does not separate during the second meiotic division, the gametes formed have too many ortoo few chro- mosomes. Defects in the cohesin pathway are responsible for many errors in chromosomal segregation. It seems reasonable to suppose that cells with three copies of chromosome 21 overproduce specific proteins that somehow modify fetal development. The challenge is to discover which genes are involved and how their gene products work. The problem is complicated because several genes may be involved. In this regard it is interesting to note that some forms of Down syndrome are caused by chromosomal rearrangements in which a segment of chromosome 21 is attached to another chromosome. In this case the individual with Down syndrome has two copies of chromosome 21 and a part of chromosome 21 attached to another chromosome. Unfortunately, the chromosome 21 segmentis still so large it is not yet possible to identify the specific genes responsible for Down syndrome. A rearrangement of chromosomal material in which part of one chromosome is joined to some other chromosome is called translocation. One of the best- characterized examples of translocation occurs in chronic myelogenous leuke- mia. Studies of chromosomes in tumor cells reveal reciprocal translocation of material from chromosome 9 to 22 to produce whatis known as the Philadelphia chromosome (FIGURE 85.1). This translocation moves a gene (ab/) from its normal location on chromosome 9 to a new location on chromosome 22, CHAPTER 5 CHROMOSOMES