14.3 Studying the Human Genome Lesson Objectives Summarize the methods of DNA analysis. State the goals of the Human Genome Project and explain what we have learned so far. Lesson Summary Manipulating DNA Since the 1970s, techniques have been developed that allow scientists to cut, separate, and replicate DNA base-by-base. Using these tools, scientists can read the base sequences in DNA from any cell. Restriction enzymes cut DNA into smaller pieces, called restriction fragments, which are several hundred bases in length. Each restriction enzyme cuts DNA at a different sequence of bases. Gel electrophoresis separates different-sized DNA fragments by placing them at one end of a porous gel, then applying an electrical voltage. The electrical charge moves the DNA. Using dye-labeled nucleotides, scientists can stop replication at any point along a single DNA strand. The fragments can then be separated by size using gel electrophoresis and read, base-by-base. The Human Genome Project was a 13-year international effort to sequence all 3 billion base pairs in human DNA and identify all human genes. The project was completed in 2003. The researchers identified markers in widely separated strands of DNA. They used shotgun sequencing, which uses a computer to match DNA base sequences. To identify genes, they found promoters, exons, and other sites on the DNA molecule. To locate and identify as many haplotypes (collections of linked single-base differences) in the human population as possible, the International HapMap Project began in 2002. The Human Genome Project identified genes associated with many diseases and disorders. From the project came the new science of bioinformatics, the creation and use of databases and other computing tools to manage data. Bioinformatics launched genomics, the study of whole genomes. The human genome project pinpointed genes and associated particular sequences in those genes with numerous diseases and disorders. It also found that the DNA of all humans matches base-for-base at most sites, but can vary at 3 million sites. The 1000 Genomes Project, launched in 2008, will catalogue the variation among 1000 people. 222
Manipulating DNA For Questions 1 4, write True if the statement is true. If the statement is false, change the underlined word to make the statement true. True 1. Bacteria produce restriction enzymes that cut the DNA molecule into smaller pieces. nucleotides 2. Restriction fragments are always cut at a particular sequence of proteins. True 3. The technique that separates differently sized DNA fragments is gel electrophoresis. polymerase 4. The enzyme that copies DNA is DNA restrictase. 5. Complete the graphic organizer to summarize the steps used to determine the sequences of bases in DNA. Purpose Tool or Technique Used Outcome Cutting DNA Restriction enzymes Large molecule of DNA is cut into smaller fragments. Separating DNA Gel electrophoresis Smaller DNA fragments move faster on the gel, so fragments are separated according to size. Reading DNA Dye-labeled nucleotides and gel electrophoresis Labeled nucleotides stop the synthesis of a new strand at different lengths. Gel electrophoresis then separates them so they can be read. For Questions 6 10, complete each statement by writing in the correct word or words. 6. By using tools that cut, separate, and then replicate DNA, scientists can now read the base sequence in DNA from any cell. 7. Restriction enzymes cut pieces of DNA sometimes called restriction fragments. 8. Each restriction enzyme cuts DNA at a different sequence of nucleotides. 9. The smaller the DNA, the faster and farther it moves during gel electrophoresis. 10. After chemically dyed bases have been incorporated into a DNA strand, the order of colored bands on the gel reveals the exact sequence of bases in DNA. 223
The Human Genome Project For Questions 11 16, write the letter of the correct answer on the line at the left. A C B D C A 11. What technology made the Human Genome Project possible? A. DNA sequencing B. RNA replication C. protein synthesis D. enzyme activation 12. What were the markers that the researchers of the Human Genome Project used? A. restriction enzymes B. gel electrophoresis C. base sequences D. restriction fragments 13. What does shotgun sequencing do? A. separate fragments using gel electrophoresis B. find overlapping areas of DNA fragments C. cut DNA into millions of puzzle pieces D. bind colored dyes to base sequences 14. What are SNPs? A. points where a restriction enzyme cuts a DNA molecule B. missing sequence of base pairs in a restriction fragment C. proteins formed by a mutated gene D. differences in a base between two individuals 15. Bioinformatics would not have been possible without A. microscopes. B. genes. C. computers. D. genomics. 16. In humans, single-base differences A. occur at about 3 million sites. B. occur rarely in the sex chromosomes. C. seldom occur in normal DNA. D. cannot be identified from DNA analysis. 17. What were the goals of the Human Genome Project? The main goals were to sequence the base pairs of DNA and identify all human genes. Other goals included sequencing genomes of model organisms, developing technology for research, exploring gene functions, studying variation in humans, and training future scientists. 224
18. The field of bioinformatics combines both life sciences and modern technology. Fill in the Venn diagram to show how. Life Science Information Science Statistics Data Analyses Experiments Observations Visualizations Computer Modeling Hypotheses Predictions Databases 19. The Icelandic people have always placed high importance on knowing about their ancestors. In fact, 80% of all the Icelandic people who have ever lived can be added to a family tree. Medical records are just as detailed. The population is quite isolated, so the gene pool is considered to be homogeneous. Why would these conditions make the genome of the Icelandic population ideal for studying rare inherited disorders associated with gene sequencing errors? The homogeneous population makes the task of finding DNA sequences easier. Unusual base pairs, such as those associated with disorders, would stand out. Since people are aware of their family s medical histories, scientists would be able to test descendants with no signs of the disorder to see just how it is inherited between generations. 225
Chapter Vocabulary Review For Questions 1 11, match the term with its definition. Definition C 1. The X chromosome or the Y chromosome E 2. A gene on the X chromosome or the Y chromosome G 3. The failure of homologous chromosomes to separate during meiosis I 4. A technology used to separate fragments of DNA F 5. A chart that shows family relationships and inheritance of traits J 6. A field of study that includes the operation of databases H 7. An enzyme that cuts a DNA molecule into small pieces K 8. The study of whole genomes, including genes and their functions B 9. A picture that shows chromosomes arranged in pairs D 10. Any chromosome that is not a sex chromosome A 11. The full set of genetic information in an organism s DNA Term A. genome B. karyotype C. sex chromosome D. autosome E. sex-linked gene F. pedigree G. nondisjunction H. restriction enzyme I. gel electrophoresis J. bioinformatics K. genomics For Questions 12 19, complete each statement by writing in the correct word or words. 12. A circle represents a female in a(n) pedigree. 13. The protein that cuts DNA into pieces is a restriction enzyme. 14. An inherited disorder that appears more often in males than females is probably caused by a sex-linked gene. 15. The 23 pairs of human chromosomes are arranged from largest to smallest in a karyotype. 16. Humans have 22 pairs of autosomes. 17. The cause of Down syndrome is nondisjunction during meiosis. 18. Humans have 3 billion base pairs in their genome. 19. The new field of bioinformatics resulted from the Human Genome Project. Chapter 14 Workbook A Copyright by Pearson Education, Inc., or its affiliates. All Rights Reserved. 226
THE CROOKED CELL In the Chapter Mystery, you learned how genetic testing can help identify risk for an inheritable disease, such as sickle-cell anemia. Geneticists have made great strides in recent years to develop many more DNA-based genetic tests. Learning NOTE: This topic may be difficult for students who are dealing with or have family members dealing with hereditary diseases. You may want to evaluate whether this exercise is appropriate for your students before assigning it. Genetic Testing: A Personal Choice Today, more than 1000 genetic tests are available to determine whether patients carry genes associated with diseases from breast cancer to the degenerative neurological disorder known as Huntington s disease. But the genetic tests pose a difficult dilemma for many people at risk for genetic disease. The choice is especially difficult for those conditions, such as Huntington s disease, for which there are no treatments or cures. Recent polls have found that a significant majority of people say they would want to undergo genetic testing for a treatable disease. But respondents remain almost evenly split on whether they would undertake testing for an untreatable condition. Many people are concerned that testing positive for an untreatable genetic disease could lead to employment discrimination, denial of medical insurance, or other types of discrimination. The National Institutes of Health has issued the following information to help people make their decisions. How Do I Decide Whether to Be Tested? People have many different reasons for being tested or not being tested. For many, it is important to know whether a disease can be prevented if a gene alteration causing a disease is found. For example, those who have inherited forms of breast or colon cancer have options such as screening or early treatment. Pharmacogenetic testing can find the best medicine or dose of a medicine for a certain person. (Pharmacogenetic testing involves the analysis of a person s genetic makeup in order to prescribe the most effective medications for that person.) But in some cases, there is no treatment or cure available. There are no preventive steps or cures for Huntington s disease, for example. Some people simply do not want to know that they will develop a serious illness for which there is no treatment or cure. Others, however, feel that knowing the test results might help them make decisions such as career choices, family planning, or insurance coverage. To help make such decisions, people can seek advice from a genetic counselor. Genetic counselors help individuals and families think about the scientific, emotional, and ethical factors that affect their decision whether or not to test. But the difficult decision is still up to the individual or family. Continued on next page Chapter 14 Workbook A Copyright by Pearson Education, Inc., or its affiliates. All Rights Reserved. 227
Themes Science and Health Literacy 1. What is a genetic test? A genetic test examines a patient s DNA to determine whether that patient carries a gene associated with a given disease. 2. How many genetic tests are currently available? more than 1000 3. According to the National Institutes of Health, why would someone want to undergo a genetic test? to find out whether a disease can be prevented, to begin early treatment, to find the best medicine or dose of a medicine, to make more appropriate decisions 4. What major factor, according to polls, affects the way people feel about a particular genetic test? People would want to undergo genetic testing for a treatable disease, but are almost evenly split on whether they would undertake genetic testing for an untreatable condition. 5. Do you think anti-discrimination laws should be put in place to protect people who test positive for an untreatable condition like Huntington s disease? Why or why not? Students may express different viewpoints, which should be supported by logical rationales. An Individual s Case The skills used in this activity include information and media literacy; communication skills; and problem identification, formulation, and solution. Use Internet or library resources to research the case of neuropsychologist Nancy Wexler. Twenty years ago, Wexler identified the gene that causes Huntington s disease. She was spurred on in her research because Huntington s disease runs in her family. Wexler spent much of her career working to develop a genetic test for Huntington s disease. But when the test finally became available, she decided that she would rather not know whether she carried the gene because no treatment exists for the disease. Organize into groups to present your findings in a panel discussion about genetic testing. Here are some questions you might consider: What are the arguments that someone should consider about the decision to undergo genetic testing? Should a genetic test even be offered for an untreatable condition like Huntington s? If so, why? Evaluate the students performance in the panel discussion based on the reasons why people want to be tested, as well as scientific, emotional, and ethical factors that affect the testing decision. Chapter 14 Workbook A Copyright by Pearson Education, Inc., or its affiliates. All Rights Reserved. 228