Ahuman diploid cell contains more than 6 billion base pairs

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1 14 2 Human Chromosomes Section FOCUS Ahuman diploid cell contains more than 6 billion base pairs of DNA. All of this DNA is neatly packed into the 46 chromosomes present in every diploid human cell. In its own way, each of these chromosomes is like a library containing hundreds or even thousands of books. Although biologists are many decades away from mastering the contents of those books, biology is now in the early stages of learning just how many books there are and what they deal with. You may be surprised to learn that genes make up only a small part of chromosomes. In fact, only about 2 percent of the DNA in your chromosomes functions as genes that is, is transcribed into RNA. Genes are scattered among long segments of DNA that do not code for RNA. The average human gene consists of about 3000 base pairs, while the largest gene in the human genome has more than 2 million base pairs! Human Genes and Chromosomes Chromosomes 21 and 22 are the smallest human autosomes. Chromosome 22 contains approximately 43 million DNA base pairs. Chromosome 21 contains roughly 32 million base pairs. These chromosomes were the first two human chromosomes whose sequences were determined. Their structural features seem to be representative of other human chromosomes. Chromosome 22 contains as many as 545 different genes, some of which are very important for health. Genetic disorders on chromosome 22 include an allele that causes a form of leukemia and another associated with neurofibromatosis, a tumor-causing disease of the nervous system. However, chromosome 22 also contains long stretches of repetitive DNA that do not code for proteins. These long stretches of repetitive DNA are unstable sites where rearrangements can occur. The structure of chromosome 21 is similar. It contains about 225 genes, including one associated with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig s disease. Chromosome 21 also has many regions with no genes at all. As exploration of the larger human chromosomes continues, molecular biologists may gradually learn more about how the arrangements of genes on chromosomes affect gene expression and development. As you may recall, genes located close together on the same chromosome are linked, meaning that they tend to be inherited together. This is true for human genes. You also read earlier that linked genes may be separated by crossing-over during meiosis; this applies to human chromosomes as well. Print: SECTION RESOURCES Teaching Resources, Lesson Plan 14 2, Adapted Section Summary 14 2, Adapted Worksheets 14 2, Section Summary 14 2, Worksheets 14 2, Section Review 14 2, Enrichment Reading and Study Workbook A, Section 14 2 Adapted Reading and Study Workbook B, Section 14 2 Key Concepts Why are sex-linked disorders more common in males than in females? What is nondisjunction, and what problems does it cause? Vocabulary sex-linked gene nondisjunction Reading Strategy: Outlining Before you read, use the headings of the section to make an outline about human chromosomes. As you read, write a sentence under each head to provide key information. Figure Lou Gehrig died at age 37 of ALS. ALS causes a progressive loss of muscle control due to the destruction of nerves in the brain and spinal cord. Issues and Decision Making, Issues and Decisions 7 Technology: BioDetectives DVD, Coming Home: A Nation s Pledge itext, Section 14 2 Animated Biological Concepts DVD, 24 Transparencies Plus, Section 14 2 Objectives Identify characteristics of human chromosomes Describe some sex-linked disorders and explain why they are more common in males than in females Explain the process of X-chromosome inactivation Summarize nondisjunction and the problems it causes. Vocabulary Preview Write the word nondisjunction on the board. Challenge students to identify the prefixes in the word. Ask: What does junction mean? (Joining together) Add the suffix dis-, and ask: What does disjunction mean? (The act of separating) Finally, challenge students to infer the meaning of nondisjunction. (The act of not separating) Reading Strategy Encourage students to add the green subheadings to their outlines and write a sentence under each. Remind students to include information in their outlines that is presented in figure captions. 2 INSTRUCT Human Genes and Chromosomes Calculating Have students reexamine the human karyotype on page 341. Ask: Which chromosomes are the largest? (1 and 2) The smallest? (18 through 22) Considering the chromosome sizes, how many bases might chromosome 1 have if chromosome 22 has about 43 million bases? (About three times as many, or 129 million) The Human Genome 349

2 14 2 (continued) Sex-Linked Genes Use Visuals Figure Discuss the symbols used in the Punnett square and relate them to pedigree. Ask: Why is the box for one son shaded? (He expresses the trait for colorblindness.) Would you expect the colorblind son to have sons who are colorblind? (No, the son can pass only the Y chromosome to his sons.) What is the probability that the daughter who is a carrier will have a colorblind child if she marries a man with normal vision? (25%) Using Models Challenge student pairs to design a pedigree that traces the inheritance of colorblindness in a family over several generations. Students can invent the family and the affected individuals. Then, students should write three questions about their pedigree and the inheritance of colorblindness. Have groups exchange pedigrees and answer the questions. X Chromosome Duchenne muscular dystrophy Melanoma X-inactivation center X-linked severe combined immunodeficiency (SCID) Colorblindness Hemophilia Y Chromosome Testis-determining factor Figure Genes on X and Y chromosomes, such as those shown in the diagrams, are called sex-linked genes. Interpreting Graphics Which chromosome carries more genes? Sex-Linked Genes Is there a special pattern of inheritance for genes located on the X chromosome or the Y chromosome? The answer is yes. Because these chromosomes determine sex, genes located on them are said to be sex-linked genes. Many sex-linked genes are found on the X chromosome, as shown in Figure More than 100 sex-linked genetic disorders have now been mapped to the X chromosome. The human Y chromosome is much smaller than the X chromosome and appears to contain only a few genes. Colorblindness Three human genes associated with color vision are located on the X chromosome. In males, a defective version of any one of these genes produces colorblindness, an inability to distinguish certain colors. The most common form of this disorder, red-green colorblindness, is found in about 1 in 10 males in the United States. Among females, however, colorblindness is rare only about 1 female in 100 has colorblindness. Why the difference? Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive. In order for a recessive allele, such as the one for colorblindness, to be expressed in females, there must be two copies of the allele, one on each of the two X chromosomes. This means that the recessive phenotype of a sex-linked genetic disorder tends to be much more common among males than among females. In addition, because men pass their X chromosomes along to their daughters, sex-linked genes move from fathers to their daughters and may then show up in the sons of those daughters, as shown in Figure Address Misconceptions Students might think that colorblind people see the world only in black and white. Show students charts used to diagnose colorblindness. Explain that a colorblind person either cannot see the object in the pattern or might see a different object. Help students realize that people who are red-green colorblind do see objects as blue or yellow or shades of red; they cannot see objects as green. Figure X-linked alleles are always expressed in males, because males have only one X chromosome. Males who receive the recessive X c allele all have colorblindness. Females, however, will have colorblindness only if they receive two X c alleles. Male Female Colorblind Normal vision Mother (carrier) X C X c X C X c X C X C X C Daughter (normal vision) X C X c Daughter (carrier) X C Y Father (normal vision) Y X C Y Son (normal vision) X c Y Son (colorblind) UNIVERSAL ACCESS Inclusion/Special Needs Have students draw diagrams to show how chromosomal disorders can occur. Make sure students realize that nondisjunction occurs during the formation of the egg cell or sperm cell. You might also have students draw Punnett squares to show the possible genotypes produced in a cross between a normal sex cell and a cell in which nondisjunction has occurred. Less Proficient Readers For each blue heading in the section, have students write a sentence that describes the main idea of that subsection. Encourage students to write the sentences in their own words, after reading the subsection and thinking about what it is about. You might also encourage students to illustrate their main ideas, if they wish. 350 Chapter 14

3 How is colorblindness transmitted? Materials 2 plastic cups, 3 white beans, black marker, red bean Procedure 1. On a sheet of paper, draw a data table with the column headings Trial, Colors, Sex of Individual, and Number of X-Linked Alleles. Draw 10 rows under the headings and fill in the numbers 1 through 10 under Trial. Use the marker to label one cup father and the other mother. 2. The white beans represent X chromosomes. Use the marker to mark a dot on 1 white bean to represent the X-linked allele for colorblindness. Place this bean, plus 1 unmarked white bean, into the cup labeled mother. 3. Mark a black dot on 1 more white bean. Place this bean, plus 1 red bean, into the cup labeled father. The red bean represents a Y chromosome. Hemophilia Hemophilia is another example of a sex-linked disorder. Two important genes carried on the X chromosome help control blood clotting. A recessive allele in either of these two genes may produce a disorder called hemophilia (hee-moh-fil-ee-uh). In hemophilia, a protein necessary for normal blood clotting is missing. About 1 in 10,000 males is born with a form of hemophilia. People with hemophilia can bleed to death from minor cuts and may suffer internal bleeding from bumps or bruises. Fortunately, hemophilia can be treated by injections of normal clotting proteins, which are now produced using recombinant DNA. Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DIS-truh-fee) is a sex-linked disorder that results in the progressive weakening and loss of skeletal muscle. In the United States, one out of every 3000 males is born with this condition. Duchenne muscular dystrophy is caused by a defective version of the gene that codes for a muscle protein. Researchers in many laboratories are trying to find a way to treat or cure this disorder, possibly by inserting a normal allele into the muscle cells of Duchenne muscular dystrophy patients. What causes Duchenne muscular dystrophy? FACTS AND FIGURES Hemophilia and royalty The frequency of hemophilia was much higher among the royal families of nineteenth-century Europe than among the general population. This was probably due to the fact that these families often intermarried. Queen Victoria of England was 4. Close your eyes and pick one bean from each cup to represent how each parent contributes a sex chromosome to a fertilized egg. 5. In your data table, record the color of each bean and the sex of an individual who would carry this pair of sex chromosomes. Also record how many X-linked alleles the individual has. Put the beans back in the cups they came from. 6. Determine whether the individual would have colorblindness. 7. Repeat steps 4 to 6 for a total of 10 pairs of beans. Analyze and Conclude 1. Drawing Conclusions How do the sex chromosomes keep the numbers of males and females roughly equal? 2. Calculating Share your data with your classmates. Calculate the class totals for each table column. How many females were colorblind? How many males? How would you explain these results? 3. Using Models Evaluate the adequacy of your model. How accurately does it represent the transmission of colorblindness in a population? a carrier of the disease, as were two of her daughters. At one time, it was calculated that of Victoria s 69 descendants, 18 were either affected males or female carriers, though none of these individuals were British. Objective Students will be able to model how colorblindness is transmitted. Skill Focus Using Models, Calculating, Drawing Conclusions Materials 2 plastic cups, 3 white beans, black marker, red bean Time 20 minutes Strategies After students read the procedure, ask: Is either parent colorblind? (Yes, the father) Is the mother heterozygous or homozygous for colorblindness? (Heterozygous) Is she a carrier? (Yes, she has one allele for colorblindness.) Remind students to keep their eyes closed while picking the beans so that they choose randomly. Expected Outcomes Students will conclude that colorblindness occurs more frequently in males because they have only one copy of the X chromosome. Analyze and Conclude 1. There is a 50 : 50 chance that a child will receive an X or Y chromosome from the father. 2. About 50% of the females will be colorblind and about 50% of the males will be colorblind. The mother is heterozygous, so her sons have a 50% chance of inheriting the X chromosome that carries the allele for colorblindness. The father is colorblind, so the daughters have a 50% chance of inheriting X chromosomes from both parents that carry the allele for colorblindness. 3. The model was accurate in representing the randomness of chromosome movement during meiosis and gametes joining during fertilization. It also accurately models the independence of each fertilization event. However, in a real population, the ratio of colorblind to noncolorblind people will be much lower, because the allele for colorblindness is not present in 50% of the people. Answers to... A defective gene that codes for a muscle protein Figure The X chromosome The Human Genome 351

4 14 2 (continued) X-Chromosome Inactivation Observing Set up microscope stations with slides of animal body cells that have Barr bodies. Encourage students to draw their observations, labeling the cell cytoplasm, nucleus, nucleoplasm, chromosomes, and Barr bodies. Then, give students two unknown slides and challenge them to identify which slide came from a female. Chromosomal Disorders Use Visuals Figure Ask: What phase of meiosis is illustrated by the first cell? (Metaphase I) If necessary, review meiosis so that students remember that in meiosis I, homologous chromosomes separate to produce a haploid cell and that in meiosis II, chromosome copies (or sister chromatids) separate. Ask: What types of gametes are produced when nondisjunction occurs? (Some gametes that have two copies of the chromosome and other gametes with no copies of it) Figure This cat s fur color is controlled by a gene on the X chromosome. Drawing Conclusions Is the cat shown a male or a female? Figure Nondisjunction causes gametes to have abnormal numbers of chromosomes. The result of nondisjunction may be a chromosome disorder such as Down syndrome. Homologous chromosomes fail to separate. Meiosis I: Nondisjunction Meiosis II X-Chromosome Inactivation Females have two X chromosomes, but males have only one. If just one X chromosome is enough for cells in males, how does the cell adjust to the extra X chromosome in female cells? The answer was discovered by the British geneticist Mary Lyon. In female cells, one X chromosome is randomly switched off. That turned-off chromosome forms a dense region in the nucleus known as a Barr body. Barr bodies are generally not found in males because their single X chromosome is still active. The same process happens in other mammals. In cats, for example, a gene that controls the color of coat spots is located on the X chromosome. One X chromosome may have an allele for orange spots and the other may have an allele for black spots. In cells in some parts of the body, one X chromosome is switched off. In other parts of the body, the other X chromosome is switched off. As a result, the cat s fur will have a mixture of orange and black spots, as shown in Figure Male cats, which have just one X chromosome, can have spots of only one color. By the way, this is one way to tell the sex of a cat. If the cat s fur has three colors white with orange and black spots, for example you can almost be certain that it is female. Chromosomal Disorders Most of the time, the mechanisms that separate human chromosomes in meiosis work very well, but every now and then something goes wrong. The most common error in meiosis occurs when homologous chromosomes fail to separate. This is known as nondisjunction, which means not coming apart. Nondisjunction is illustrated in Figure If nondisjunction occurs, abnormal numbers of chromosomes may find their way into gametes, and a disorder of chromosome numbers may result. Down Syndrome If two copies of an autosomal chromosome fail to separate during meiosis, an individual may be born with three copies of a chromosome. This is known as a trisomy, meaning three bodies. The most common form of trisomy involves three copies of chromosome 21 and is called Down syndrome. Figure shows a karyotype of a person with Down syndrome. In the United States, approximately 1 baby in 800 is born with Down syndrome. Down syndrome produces mild to severe mental retardation. It is also characterized by an increased susceptibility to many diseases and a higher frequency of some birth defects. Why should an extra copy of one chromosome cause so much trouble? That is still not clear, and it is one of the reasons scientists have worked so hard to learn the DNA sequence for chromosome 21. Now that researchers know all of the genes on the chromosome, they can begin experiments to find the exact genes that cause problems when present in three copies. HISTORY OF SCIENCE Barr bodies Barr bodies were named for Murray Barr, who first observed them in the nerve cells of female cats in It was not until the early 1960s that Mary Lyon proposed that one X chromosome is randomly inactivated. In body cells, she observed that one X chromosome replicated later than the other. The late-replicating X chromosome is inactivated when the embryo implants in the uterine wall. All body cells have the same activated and inactivated X chromosomes as the embryonic cell from which they were derived. 352 Chapter 14

5 Sex Chromosome Disorders Disorders also occur among the sex chromosomes. Two of these abnormalities are Turner s syndrome and Klinefelter s syndrome. In females, nondisjunction can lead to Turner s syndrome. A female with Turner s syndrome usually inherits only one X chromosome (karyotype 45,X). Women with Turner s syndrome are sterile, which means that they are unable to reproduce. Their sex organs do not develop at puberty. In males, nondisjunction causes Klinefelter s syndrome (karyotype 47,XXY). The extra X chromosome interferes with meiosis and usually prevents these individuals from reproducing. Cases of Klinefelter s syndrome have been found in which individuals were XXXY or XXXXY. There have been no reported instances of babies being born without an X chromosome, indicating that the X chromosome contains genes that are vital for the survival and development of an embryo. These sex chromosome abnormalities point out the essential role of the Y chromosome in male sex determination in humans. The human Y chromosome contains a sex-determining region that is necessary to produce male sexual development, and it can do this even if several X chromosomes are present. However, if this region of the Y chromosome is absent, the embryo develops as a female. Figure The karyotype on the right is from a person with Down syndrome. Down syndrome causes mental retardation and various physical problems. People with Down syndrome can, however, lead active, happy lives. Observing Analyze this karyotype. What characteristic enables you to identify it as belonging to a person with Down syndrome? Is that person male or female? Drawing Conclusions From patients with sex chromosomes disorders, physicians and geneticists have been able to infer the functions of the X and Y chromosomes to sex determination. Ask: Why do geneticists believe that the X chromosome contains genes that are vital for survival? (Babies without an X chromosome have never been born.) Why is the Y chromosome thought to cause male sexual development? (In the absence of a Y chromosome, the embryo develops as a female.) 3 ASSESS Evaluate Understanding Have students construct a concept map that summarizes the concepts described in this section. Students should include the Vocabulary terms and Key Concepts in the map. Reteach Have students use Punnett squares to model how sex-linked traits are transmitted from parents to offspring. Challenge students to show how a dominant sex-linked allele has a different pattern of inheritance from a recessive sex-linked allele Section Assessment 1. Key Concept Why are sex-linked disorders more common in males than in females? 2. Key Concept How does nondisjunction cause chromosome number disorders? 3. List at least two examples of human sex-linked disorders. 4. Describe two sex chromosome disorders. 5. Critical Thinking Comparing and Contrasting Distinguish between sex-linked disorders and sex chromosome disorders. Explaining a Process Write a paragraph explaining the process of nondisjunction. Hint: To organize your writing, refer to Figure and use this diagram to create a flowchart that shows the steps in the process. Paragraphs should describe in a step-by-step process the failure of one pair of homologous chromosomes to separate during anaphase I or the failure of one pair of chromatids to separate during anaphase II Section Assessment If your class subscribes to the itext, use it to review the Key Concepts in Section Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive. 2. Chromosomes fail to separate, causing gametes to have abnormal numbers of chromosomes. 3. Answers include colorblindness, hemophilia, and Duchenne muscular dystrophy. 4. A female with Turner s syndrome has only one X chromosome and is sterile. A male with Klinefelter s syndrome has one or more extra X chromosomes and is usually sterile. 5. Sex-linked disorders are caused by alleles of genes usually carried on the X chromosome. Sex chromosome disorders are caused by nondisjunction, or sex chromosomes failing to separate correctly during meiosis. Answers to... Figure The cat is female. Figure Since it has three copies of chromosome 21, it is the karyotype of a person with Down syndrome; the two X chromosomes indicate a female. The Human Genome 353

6 Who Controls Your DNA? Encourage one group of students to learn what companies or agencies are interested in knowing about an individual s DNA. Students should find out what the motives of these agencies and companies are. Have another group of students learn about medical records and who has access to that information. A third group of students can research how DNA information has allegedly been used to discriminate against individuals. Have each group present its findings to the class. Then, have a class discussion about the pros and cons of keeping DNA information private. Research and Decide 1. Accept all reasonable answers. Justified: Employers use DNA information as a record of employees identity, as in the case of the military. Withhold: Individuals are concerned that DNA information could be used against them, causing them to lose promotions or even their jobs. 2. Students will have different opinions, but all opinions should include reasonable explanations. 3. Some students might think the insurance company has a right to test for cystic fibrosis so that it can decide not to insure a family carrying the allele to prevent a profit loss. Others might think the insurance company does not have the right to test for the cystic fibrosis allele, because DNA information is private and should not be used to discriminate against an individual. The U.S. Department of Defense requires that soldiers submit DNA samples for a database that could be used to identify soldiers remains. Two Marines, Corporal John C. Mayfield and Corporal Joseph Vlacovsky, refused. At their court martial, the two Marines argued that DNA samples could be examined for genes related to disease or even behavior and, therefore, the database was an invasion of privacy. As a result of the concerns raised by this case, the U.S. Department of Defense has changed its policies. It now destroys DNA samples upon request when an individual leaves military service. Do people have a right to control their own DNA samples? The Viewpoints DNA Information Is Not Private As the court recognized, the U.S. Department of Defense had good reasons for requiring that DNA samples be taken and stored. Furthermore, DNA sequences are no more private and personal than fingerprints or photographs, which are taken by private and government agencies all the time. An employer has a right to take and keep such information. Individuals should have no reason to fear the abuse of such databases. DNA Infomation Is Private and Personal The use of DNA for personal identification by the military may be justified. An individual s genetic information, however, is a private matter. A recent study at Harvard and Stanford universities turned up more than 200 cases of discrimination because of genes individuals carried or were suspected of carrying. Employers with DNA information might use it to discriminate against workers who carry genes they suspect might cause medical or behavioral problems. Individuals must have the right to control their own DNA and to withhold samples from such databases. Research and Decide 1. Analyzing the Viewpoints Learn more about this issue by consulting library or Internet resources. Then decide whether there are any circumstances in which an employer might be justified in demanding DNA samples from its employees. Why might an employee wish to withhold such samples? 2. Forming Your Opinion Should the control of DNA databases be a matter of law, or should it be a matter to be negotiated between people, their employers, and insurance companies? 3. Persuasive Speaking Suppose you were a doctor working as a consultant to a health insurance company. The insurance company is trying to decide whether to test adults for cystic fibrosis alleles before agreeing to insure their families. What advice would you give to the company about this? For: Links from the authors Visit: PHSchool.com Web Code: cbe-4142 Students can research the right to control DNA information on the site developed by authors Ken Miller and Joe Levine. 354 Chapter 14