Human genetics, concepts and applications 5th ed lewis (mcgraw, 2003)

Lewis: Human Genetics Concepts and Applications, Fifth Edition Front Matter Preface © The McGraw−Hill Companies, 2003 Preface Introduction Very few events in human history can be said, in retrospect, to divide time September 11, 2001, is one such date I was revising this edition on that bright and clear Tuesday morning, looking forward to penning an upbeat preface celebrating the human genome annotation proceeding in various laboratories It was not to be Now as I write this, the largest such lab is instead applying the high-throughput DNA sequencing that it used to sequence the human genome to analyzing thousands of bits of teeth and bones that arrive daily in evidence bags Somber lab workers are extracting the mitochondrial DNA that persists after the genetic material of softer tissues is obliterated by fire and crushing pressure Earlier, closer to that date that divided time, DNA fingerprinters at another biotech company probed softer samples shipped from the wreckage, along with cheekbrush samples bearing DNA from relatives, and bits of skin and hair left clinging to toothbrushes and hairbrushes and clothing on a day that everyone thought would be like any other It was an astonishing and horrifying contrast to the depiction of DNA fingerprinting in the first chapter of the fourth edition of this book—tracing the ancestry of wine grapes Times have changed With DNA sequencing subverted to a purpose that no one could have predicted, revising a textbook didn’t, at first, seem very important anymore But in the weeks that followed September 11, as the belated recognition and response to bioterrorism exposed a frighteningly pervasive lack of knowledge of basic biology among our leaders, the importance of the average citizen’s understanding of what genes are and what they emerged At the same time, new questions arose Should researchers xiv continue to publish new genome sequences? Suddenly, those wondrous reports of unexpected gene discoveries mined from microbial genomes held the seeds of potential weaponry Times have changed Before September 11, politicians hotly debated stem cells, renegade scientists touted their human cloning efforts, and environmentalists donned butterfly suits and destroyed crops to protest the perceived threat of corn genetically altered to escape the jaws of caterpillars Gene therapy struggled to regain its footing in the wake of a tragic death in 1999, while a spectacularly successful new cancer drug, based on genetic research, hit the market With time, interest in these areas will return, and maybe we will even begin to care again about the ancestry of wine grapes Human Genetics: Concepts and Applications, fifth edition will guide the reader in understanding genetics and genomics and applying it to daily life That has not changed What’s New and Exciting About This Edition Focus on Genomics—Of SNPs, Chips, and More While Mendel’s laws, the DNA double helix, protein synthesis and population dynamics will always form the foundation of genetics, the gradual shift to a genomic view opens many new research doors, and introduces new ways of thinking about ourselves Completion of the human genome draft sequence has catapulted human genetics from the one-gene-at-a-time approach of the last half of the last century to a more multifactorial view Genes and the environment interact to mold who we are It is a little like jumping from listening Lewis: Human Genetics Concepts and Applications, Fifth Edition Front Matter to individual instruments to experiencing a symphony created by an entire orchestra The fourth edition of Human Genetics: Concepts and Applications introduced genomics; in the fifth edition, the impact of this new view of genes is so pervasive that it is integrated into many chapters, rather than saved for a final chapter Rather than bludgeon the reader with details, acronyms and jargon, the approach to genomics is in context—association studies in chapter 7, human genome annotation in chapter 10, filling in chromosome details in chapter 12, and glimpses into human evolution in chapter 15 Immunity is presented in chapter 16 from the point of view of the pathogen, courtesy of genomes Because of the integration of the genomic view throughout the text, the final chapter is free to tell the story of how this view came to be—and where it will go • Mood disorders (depression and bipolar disorder) • Schizophrenia The chapter is entirely new, with many compelling examples from the biomedical literature and interviews with researchers Fabulous New Art Long-time users of Human Genetics: Concepts and Applications will note at a glance that all of the art is new Vibrant new colors and closer attention to clarity of concepts ease the learning experience and make studying this complex subject less intimidating Some of the figures are also available as Active Art, which enables the learner to manipulate portions of the illustration to review the steps to a process Entirely new illustrations include: 7.11 New Chapter on Behavior The evolution of genetic thought, from a Mendelian paradigm to a much broader consideration of genes against a backdrop of environmental influences, is perhaps nowhere more evident than in the study of human behavior With each edition, coverage of behavior has expanded until, like a cell accumulating cytoplasm, a division was in order The resulting binary fission of the fourth edition’s chapter 7—Multifactorial and Behavioral Traits—naturally yielded a chapter on methods and basic concepts, and another on specific interesting behaviors Chapter in this fifth edition, Multifactorial Traits, retains the classical adoption/twin/empiric risk approaches, and introduces association studies, which are critical in analyzing the traits and disorders described in depth in chapter 8, The Genetics of Behavior The topics for chapter came from two general sources—my curiosity, and information from several human genome conferences held since 2000 The chapter opens with a focus on new types of evidence about the role of genes in behavior, then applies these new tools to dissect the genetic underpinnings of: • • • • Eating disorders Sleep Intelligence Drug addiction © The McGraw−Hill Companies, 2003 Preface Association studies are correlations of SNP profiles 8.6 How alcohol alters gene expression in the brain 10.18 One prion, multiple conformations 10.19 Proteomics meets medicine 10.20 Exon shuffling expands gene number 10.21 Genome economy occurs in several ways 11.12 Myotonic dystrophies—novel mutation mechanism 12.4 Subtelomeres 15.8 A human HOX mutation causes synpolydactyly 15.11 Probing the molecules of extinct organisms 16.19 M cells set up immunity in the digestive tract 19.1,2,3 Three gene therapies 20.9 The global GM foods picture 22.4 Two routes to the human genome sequence 22.9 Genome sequencing, from start to finish 22.10 Comparative genomics Several new photos put faces on genetic diseases Tables Tell the Tale A student reviewing for an impending exam should be able to get the gist of a chapter in 10 minutes by examining the tables—if the tables are appropriately chosen and pre- sented, as they are in this book Table 8.5, for example, reviews every behavioral trait or disorder discussed in this new chapter, in the order of the subsections Most tables summarize and organize facts, easing studying A few tables add information (table 12.1 Five Autosomes, table 14.1 Founder Populations; table 16.8 Sequenced Genomes of Human Pathogens), and some provide perspective (table 1.1 Effects of Genes on Health) Chapter 10, Gene Action and Expression, a top candidate for “toughest chapter,” illustrates how the tables tell the tale: Table 10.1 Table 10.2 Table 10.3 Table 10.4 Table 10.5 How RNA and DNA Differ Major Types of RNA Deciphering RNA Codons and the Amino Acids They Specify The Genetic Code The Non-protein Encoding Parts of the Genome The final table in chapter 10 is new, a summary of answers to the question, certain to be posed by students and instructors alike, “If less than percent of the genome encodes protein, what does the rest of it do?” This is a table that will obviously evolve with each edition as we learn more New “In Their Own Words” and Bioethics Boxes “In Their Own Words” essays are written by individuals who experience inherited disease, as patients, family members, or researchers New essays in the fifth edition introduce: • Patricia Wright, who only recently discovered that she has had signs and symptoms of alkaptonuria all her life (chapter 5) • Francis Barany, a microbiologist who nearly burned his leg off searching for heat-loving bacteria with useful enzymes in a Yellowstone Park hot springs (chapter 9) • Toby Rodman, an immunologist and octogenarian who discovered a new source of antibodies that may protect against HIV infection (chapter 16) They join from past editions Don Miller, the first recipient of gene therapy for hemophilia; Stefan Schwartz, who has Klinefelter Preface xv Lewis: Human Genetics Concepts and Applications, Fifth Edition Front Matter disease, and Kathy Naylor, whose little girl died of cri-du-chat syndrome Bioethics: Choices for the Future essays continue their look at controversies that arise from genetic technology These essays explore population databases (chapter 1), cloning and stem cell research (chapter 3), sex reassignment (chapter 6), xenotransplants (chapter 16), Canavan disease as a test of fair use of genetic tests (chapter 19) and GM foods (chapter 20) Bioethical issues weave throughout the narrative as well New section 21.4, for example, examines the dilemma of what to with in vitro fertilized “spares.” Significant Changes in Content The two obvious changes in content are the addition of a chapter devoted to behavior, and a substantial new section in chapter 10, “The Human Genome Sequence Reveals Unexpected Complexity.” This section is essentially a summary of the mid-February 2001 issues of Science and Nature, which covered the annotation of the draft human genome sequence, aka “the golden path.” The rest of the chapter has been rewritten to embrace the new genome information as well Favorite examples and stories have been retained, and new ones added, many gleaned from my articles in The Scientist They include: • A breast cancer DNA “chip” that predicts which drugs will work on which women (chapter 1) • Greatly expanded coverage of stem cells (chapters and 3) • Relationship between Mendel’s second law and DNA microarrays (chapter 4) • Clearer coverage of mitochondrial genes (chapter 5) • Moved and expanded coverage of DNA repair (chapter 11) • Updates on chromosome structure with new coverage of centromeres and subtelomeres (chapter 12) • Applications of DNA fingerprinting to events of 9-11-01 (chapter 13) • New coverage of genetic basis of resistance to AIDS drugs (chapter 14) • New section on genome distinctions between humans and chimps (chapter 15) xvi Preface Preface • Genome information applied to immunity, with new sections on crowd diseases, bioweapons, and pathogen genomes (chapter 16) • Genetic modification of pig excrement to reduce pollution (chapter 18) • Gene therapy for Canavan disease (chapter 19) • Impact of genomics on agricultural biotechnology (chapter 20) • History of the human genome project (chapter 22) Supplements As a full service publisher of quality educational products, McGraw-Hill does much more than just sell textbooks to your students We create and publish an extensive array of print, video, and digital supplements to support instruction on your campus Orders of new (versus used) textbooks help us to defray the cost of developing such supplements, which is substantial Please consult your local McGraw-Hill representative to learn about the availability of the supplements that accompany Human Genetics: Concepts and Applications For the Student Online Learning Center Get online at www.mhhe.com/lewisgenetics5 Explore this dynamic site designed to help you get ahead and stay ahead in your study of human genetics Some of the activities you will find on the website include: Self-quizzes to help you master material in each chapter Flash cards to ease learning of new vocabulary Case Studies to practice application of your knowledge of human genetics Links to resource articles, popular press coverage, and support groups Genetics: From Genes to Genomes CD-ROM This easy-to-use CD covers the most challenging concepts in the course and makes them more understandable through presentation of full-color animations and interactive exercises Icons in the text indicate related topics on the CD © The McGraw−Hill Companies, 2003 Case Workbook in Human Genetics, third edition by Ricki Lewis, ISBN 0-07246274-4 This workbook is specifically designed to support the concepts presented in Human Genetics through real cases adapted from recent scientific and medical journals, with citations included With cases now specifically related to each chapter in the book, the workbook provides practice for constructing and interpreting pedigrees; applying Mendel’s laws; reviewing the relationships of DNA, RNA, and proteins; analyzing the effects of mutations; evaluating phenomena that distort Mendelian ratios; designing gene therapies; and applying new genomic approaches to understanding inherited disease An Answer Key is available for the instructor For the Instructor Online Learning Center Find complete teaching materials online at www.mhhe.com/lewisgenetics5 including: A complete Instructor’s Manual, prepared by Cran Lucas of Louisiana State University, is available online Download the complete document or use it as a chapter resource as you prepare lectures or exams Features of the manual include: Chapter outlines and overviews Chapter-by-chapter resource guide to use of visual supplements Answers to questions in the text Additional questions and answers for each chapter Internet resources and activities Downloadable Art is provided for each chapter in jpeg format for use in class presentations or handouts In this edition, every piece of art from the text is provided as well as every table, and a number of photographs Instructors will also find a link to Pageout: The Course Website Development Center to create your own course website Pageout’s powerful features help create a customized, professionally designed website, yet it is incredibly easy to use There is no need to know any coding Save time and valuable resources by typing your course information into the easy-to-follow templates Test Item File Multiple choice questions and answers that may be used in test- Lewis: Human Genetics Concepts and Applications, Fifth Edition Front Matter ing are provided for each chapter Prepared by Cran Lucas of Louisiana State University, this resource covers the important concepts in each chapter and provides a variety of levels of testing The file is available through PageOut and is also available on a crossplatform CD to adopters of the text Overhead Transparencies A set of 100 full-color transparencies showing key illustrations from the text is available for adopters Additional images are available for downloading from the text website Digital Content Manager New to this edition is an instructor’s CD containing a powerful visual package for preparing your lectures in human genetics On this CD, you will find: All Text Art in a format compatible with presentation or word processing software Powerpoint Presentations covering each chapter of the text New Active Art! Build images from simple to complex to suit your lecture style Acknowledgments Many heartfelt thanks to Deborah Allen for guiding yet another edition of this, my favorite book, and to Joyce Berendes and Carol Kromminga and the superb artists at Precision Graphics for making this book possible Many thanks also to my wonderful family, cats, guinea pigs, and Speedy the relocated tortoise Reviewers Many improvements in this edition are a direct result of the suggestions from reviewers and diarists who provided feedback for this edition and previous editions of Human Genetics: Concepts and Applications To each of them, a sincere thanks We also thank the students in Ruth Sporer’s Human Genetics class at the University of Pennsylvania for their review of the fourth edition, Ivan E Leigh of West Chester, Pennsylvania for his careful review of the manuscript from the perspective of a mature student, and Clifton Poodry, Director of Minority Opportunities in Research Division of NIH, for his advice Preface about handling issues of diversity and difference with sensitivity throughout the book Reviewers for This Edition Michael Appleman University of Southern California Ruth Chesnut Eastern Illinois University Meredith Hamilton Oklahoma State University Martha Haviland Rutgers University Trace Jordan New York University A Jake Lusis University of California at Los Angeles Charlotte K Omoto Washington State University Bernard Possidente Skidmore College Ruth Sporer University of Pennsylvania John Sternick Mansfield University Dan Wells University of Houston We also thank these instructors for their thoughtful feedback on the Fourth Edition Sidney L Beck DePaul University Hugo Boschmann Hesston College Hessel Bouma III Calvin College David Fan University of Minnesota Russ Feirer St Norbert College Rosemary Ford Washington College Gail E Gasparich Towson University Werner Heim The Colorado College Tasneem F Khaleel Montana State University–Billings Marion Klaus Sheridan College–Wyoming Ann Hofmann Madisonville Community College Thomas P Lehman Morgan Community College © The McGraw−Hill Companies, 2003 Tyre J Proffer Kent State University Shyamal K Majumdar Lafayette College James J McGivern Gannon University Philip Meneely Haverford College Karen E Messley Rock Valley College Nawin C Mishra University of South Carolina Grant G Mitman Montana Tech of The University of Montana Venkata Moorthy Northwestern Oklahoma State University Tim Otter Albertson College of Idaho Oluwatoyin O Osunsanya Muskingum College Joan M Redd Walla Walla College Dorothy Resh University of St Francis Nick Roster Eastern Wyoming College Lisa M Sardinia Pacific University Brian W Schwartz Columbus State University Jeanine Seguin Keuka College Keith L Sternes Sul Ross State University Edwin M Wong Western Connecticut State University Reviewers for Previous Editions Michael Abruzzo California State University at Chico Mary K Bacon Ferris State University Susan Bard Howard Community College Sandra Bobick Community College of Allegheny County Robert E Braun University of Washington James A Brenneman University of Evansville Virginia Carson Chapman University Mary Curtis, M.D University of Arkansas at Little Rock Preface xvii Lewis: Human Genetics Concepts and Applications, Fifth Edition Mary Beth Curtis Tulane University Ann Marie DiLorenzo Montclair State College Frank C Dukepoo Northern Arizona University Robert Ebert Palomar College Larry Eckroat Pennsylvania State University at Erie Jack Fabian Keene State College David Fromson California State University–Fullerton Elizabeth Gardner Pine Manor College Michael A Gates Cleveland State University Donald C Giersch Triton College Miriam Golomb University of Missouri–Columbia Meredith Hamilton Oklahoma State University Greg Hampikian Clayton College and State University George A Hudock Indiana University Neil Jensen Weber State College William J Keppler Florida International University Valerie Kish University of Richmond xviii Preface Front Matter Preface Arthur L Koch Indiana University Richard Landesman University of Vermont Mira Lessick Rush University Cran Lucas Louisiana State University at Shreveport Jay R Marston Lane Community College Joshua Marvit Penn State University James J McGivern Gannon University Denise McKenney University of Texas of the Permian Basin Wendell H McKenzie North Carolina State University Mary Rengo Murnik Ferris State University Michael E Myszewski Drake University Donald J Nash Colorado State University Charlotte K Omoto Washington State University David L Parker Northern Virginia Community College— Alexandria Campus Jack Parker Southern Illinois University at Carbondale Michael James Patrick Seton Hill College © The McGraw−Hill Companies, 2003 Bernard Possidente Skidmore College Albert Robinson SUNY at Potsdam Peter A Rosenbaum SUNY–Oswego Peter Russel Chaffey College Polly Schulz Portland Community College Georgia Floyd Smith Arizona State University Jolynn Smith Southern Illinois University at Carbondale Anthea Stavroulakis Kingsborough Community College Margaret R Wallace University of Florida Robert Wiggers Stephen F Austin State University Roberta B Williams University of Nevada–Las Vegas H Glenn Wolfe University of Kansas Virginia Wolfenberger Texas Chiropractic College Janet C Woodward St Cloud State University Connie Zilles West Valley College Lewis: Human Genetics Concepts and Applications, Fifth Edition I Introduction © The McGraw−Hill Companies, 2003 Overview of Genetics Part One Introduction C Overview of Genetics 1.1 A Look Ahead Testing for inherited diseases and susceptibilities will become standard practice as health care becomes increasingly individualized Tests that detect specific variations in genetic material will enable physicians to select treatments that a person can tolerate and that are the most likely to be effective 1.2 From Genes to Genomes DNA sequences that constitute genes carry information that tells cells how to manufacture specific proteins A gene’s effects are evident at the cell, tissue, organ, and organ system levels Traits with large inherited components can be traced and predicted in families Genetic change at the population level underlies evolution Comparing genomes reveals that humans have much in common with other species H A P T E R 1.3 Genes Do Not Usually Function Alone In the twentieth century, genetics dealt almost entirely with single-gene traits and disorders Today it is becoming clear that multiple genes and the environment mold most traits 1.4 Geneticists Use Statistics to Represent Risks Risk is an estimate of the likelihood that a particular individual will develop a particular trait It may be absolute for an individual, or relative based on comparison to other people 1.5 Applications of Genetics Genetics impacts our lives in diverse ways Genetic tests can establish identities and diagnose disease Genetic manipulations can provide new agricultural variants Lewis: Human Genetics Concepts and Applications, Fifth Edition I Introduction Genetics is the study of inherited variation and traits Sometimes people confuse genetics with genealogy, which considers relationships but not traits With the advent of gene-based tests that can predict future disease symptoms, some have even compared genetics to fortune telling! But genetics is neither genealogy nor fortune telling—it is a life science Although genetics is often associated with disease, our genes provide a great variety of characteristics that create much of our individuality, from our hair and eye color, to the shapes of our body parts, to our talents and personality traits Genes are the units of heredity, the sets of biochemical instructions that tell cells, the basic units of life, how to manufacture certain proteins These proteins ultimately underlie specific traits; a missing protein blood-clotting factor, for example, causes the inherited disease hemophilia A gene is composed of the molecule deoxyribonucleic acid, more familiarly known as DNA Some traits are determined nearly entirely by genes; most traits, however, have considerable environmental components The complete set of genetic information characteristic of an organism, including proteinencoding genes and other DNA sequences, constitutes a genome Genetics is unlike other life sciences in how directly and intimately it affects our lives It obviously impacts our health, because we inherit certain diseases and disease susceptibilities But principles of genetics also touch history, politics, economics, sociology, and psychology, and they force us to wrestle with concepts of benefit and risk, even tapping our deepest feelings about right and wrong A field of study called bioethics was founded in the 1970s to address many of the personal issues that arise in applying medical technology Bioethicists have more recently addressed concerns that new genetic knowledge raises, issues such as privacy, confidentiality, and discrimination An even newer field is genomics, which considers many genes at a time The genomic approach is broader than the emphasis on single-gene traits that pervaded genetics in the twentieth century It also enables us to compare ourselves to other species—the similarities can be astonishing and quite humbling! New technology has made genomics possible Researchers began deciphering genomes Part One Introduction Overview of Genetics in 1995, starting with a common bacterium Some three dozen genome projects later, by 2000, a private company and an international consortium of researchers added Homo sapiens to the list, with completion of a “first draft” sequence of the human genome The genomes of more than 100 species have been sequenced It will take much of the new century to understand our genetic selves Following is a glimpse of how two young people might encounter genomics in the not-too-distant future All of the tests mentioned already exist 1.1 A Look Ahead The year is 2005 Human genomics has not yet progressed to the point that newborns undergo whole-genome screens—that is still too expensive—but individuals can take selected gene tests tailored to their health histories Such tests can detect gene variants that are associated with increased risk of developing a particular condition Young people sometimes take such tests—if they want to—when there are ways to prevent, delay, or control symptoms Consider two 19year-old college roommates who choose to undergo this type of genetic testing Mackenzie requests three panels of tests, based on what she knows about her family background An older brother and her father smoke cigarettes and are prone to alcoholism, and her father’s mother, also a smoker, died of lung cancer Two relatives on her mother’s side had colon cancer Mackenzie also has older relatives on both sides who have Alzheimer disease She asks for tests to detect genes that predispose her to developing addictions, certain cancers, and inherited forms of Alzheimer disease Laurel, Mackenzie’s roommate, requests a different set of tests, based on her family history She has always had frequent bouts of bronchitis that often progress to pneumonia, so she requests a test for cystic fibrosis (CF) Usually a devastating illness, CF has milder forms whose symptoms are increased susceptibility to respiratory infections These cases often go unrecognized as CF, as Laurel knows from reading a journal article for a biology class last year Because her sister and mother also get bronchitis often, she suspects mild CF in the family Laurel requests tests for type II (noninsulin-dependent) diabetes mellitus, be- © The McGraw−Hill Companies, 2003 cause several of her relatives developed this condition as adults She knows that medication can control the abnormal blood glucose level, but that dietary and exercise plans are essential, too If she knows she is at high risk of developing the condition, she’ll adopt these habits right away However, Laurel refuses a test for inherited susceptibility to Alzheimer disease, even though a grandfather died of it She does not want to know if this currently untreatable condition is likely to lie in her future Because past blood tests revealed elevated cholesterol, Laurel seeks information about her risk of developing traits associated with heart and blood vessel (cardiovascular) disease Each student proceeds through the steps outlined in figure 1.1 The first step is to register a complete family history Next, each young woman swishes a cotton swab on the inside of her cheek to obtain cells, which are then sent to a laboratory for analysis There, DNA is extracted and cut into pieces, then tagged with molecules that fluoresce under certain types of light The students’ genetic material is then applied to “DNA chips,” which are small pieces of glass or nylon to which particular sequences of DNA have been attached Because the genes on the chip are aligned in fixed positions, this device is also called a DNA microarray A typical DNA microarray bears hundreds or even thousands of DNA pieces One of Mackenzie’s DNA chips bears genes that regulate her circadian (daily) rhythms and encode the receptor proteins on nerve cells that bind neurotransmitters If Mackenzie encounters addictive substances or activities in the future, having certain variants of these genes may increase her risk of developing addictive behaviors Another DNA chip screens for gene variants that greatly increase risk for lung cancer, and a third DNA chip detects genes associated with colon cancer Her fourth DNA chip is smaller, bearing the genes that correspond to four types of inherited Alzheimer disease Laurel’s chips are personalized to suit her family background and specific requests The microarray panel for CF is straightforward—it holds 400 DNA sequences corresponding to variants of the CF gene known to be associated with the milder symptoms that appear in Laurel’s family The microarray for diabetes bears gene variants that reflect how Laurel’s body Lewis: Human Genetics Concepts and Applications, Fifth Edition I Introduction © The McGraw−Hill Companies, 2003 Overview of Genetics Step 1: Research and record family history Mackenzie Laurel Step 2: Provide cell sample Step 3: Sample DNA isolated and applied to personalized DNA chips Trait Risk Trait Risk Addictive behavior Greater than general population Greater than general population Less than general population Less than general population Cystic fibrosis 100% diagnosis Type II diabetes mellitus Cardiovascular disease Less than general population Greater than general population Lung cancer Colon cancer Alzheimer disease Step 4: Results calculated, communicated Mackenzie’s Genetic Profile Laurel’s Genetic Profile figure 1.1 Genetic testing Tests like these will soon become a standard part of health care handles glucose transport and uptake into cells The DNA microarray for cardiovascular disease is the largest and most diverse It includes thousands of genes whose protein products help to determine and control blood pressure, blood clotting, and the synthesis, transport, and metabolism of cholesterol and other lipids A few days later, the test results are in, and a very important part of the process occurs—meeting a genetic counselor, who explains the findings Mackenzie learns that she has inherited several gene variants that predispose her to addictive behaviors and to developing lung cancer—a dangerous combination But she does not have genes that increase her risk for inherited forms of colon cancer or Alzheimer disease Mackenzie is relieved She knows to avoid alcohol and especially smoking, but is reassured that her risks of inherited colon cancer and Alzheimer disease are no greater than they are for the general population— in fact, they are somewhat less Laurel finds out that she indeed has a mild form of cystic fibrosis The microarray also indicates which types of infections she is most susceptible to, and which antibiotics will most effectively treat her frequent episodes of bronchitis and pneumonia She might even be a candidate for gene therapy— periodically inhaling a preparation containing the normal version of the CF-causing gene engineered into a “disabled” virus that would otherwise cause a respiratory infection The diabetes test panel reveals a risk that is lower than that for the general population Laurel also learns she has several gene variants that raise her blood cholesterol level By following a diet low in fat and high in fiber, exercising regularly, and frequently checking her cholesterol levels, Laurel can Chapter One Overview of Genetics Lewis: Human Genetics Concepts and Applications, Fifth Edition I Introduction help keep her heart and blood vessels healthy On the basis of the cardiovascular disease microarray panel, her physician can also tell which cholesterol-lowering drug she will respond to best, should lifestyle changes be insufficient to counter her inherited tendency to accumulate cholesterol and other lipids in the bloodstream The DNA microarray tests that Mackenzie and Laurel undergo will become part of their medical records, and tests will be added as their interests and health status change For example, shortly before each young woman tries to become pregnant, she and her partner will take prenatal DNA microarray panels that detect whether or not they are carriers for any of several hundred illnesses, tailored to their family backgrounds and ethnic groups Carriers can pass an inherited illness to their offspring even when they are not themselves affected If Laurel, Mackenzie or their partners carry inherited conditions, DNA microarray tests can determine whether their offspring inherit the illness Impending parenthood isn’t the only reason Laurel and Mackenzie might seek genetic testing again If either young woman suspects she may have cancer, for example, DNA microarrays called expression panels can determine which genes are turned on or off in affected cells compared to nonaffected cells of the same type Such information can identify cancer cells very early, when treatment is more likely to work These devices also provide information on how quickly the disease will progress, and how tumor cells and the individual’s immune system are likely to respond to particular drugs A DNA microarray can reveal that a particular drug will produce intolerable side effects before the patient has to experience that toxicity The first DNA microarray to analyze cancer, the “lymphochip,” was developed before completion of the human genome project It identifies cancer-causing and associated genes in white blood cells A different DNA microarray test, for breast cancer, is used on samples of breast tissue to track the course of disease and assess treatment The “chip” was featured on a cover of Nature magazine with the headline, “portrait of a breast cancer.” In one experiment, DNA microarray tests were performed on tumor cells of 20 women with advanced Part One Introduction © The McGraw−Hill Companies, 2003 Overview of Genetics breast cancer before and after a 3-month regimen of chemotherapy The gene pattern returned to normal only in the three women who ultimately responded to the treatment, demonstrating the test’s predictive power Though Laurel and Mackenzie will gain much useful information from the genetic tests, their health records will be kept confidential Laws prevent employers and insurers from discriminating against anyone based on genetic information This is a practical matter—everyone has some gene variants that are associated with disease With completion of the human genome project, the medical world is exploding with new information One company has already invented a five-inch by five-inch wafer that houses up to 400 DNA microarrays, each the size of a dime and containing up to 400,000 DNA pieces New health care professionals are being trained in genetics and the new field of genomics; older health care workers are also learning how to integrate new genetic knowledge into medical practice Another change is in the breadth of genetics In the past, physicians typically encountered genetics only as rare disorders caused by single genes, such as cystic fibrosis, sickle cell disease, and muscular dystrophy, or chromosome disorders, such as trisomy 21 Down syndrome Today, medical science is beginning to recognize the role that genes play in many types of conditions (table 1.1) A study of the prevalence of genetic disorders among 4,224 children admitted to Rainbow Babies and Children’s Hospital in Cleveland in 1996 revealed that genes con- tribute much more to disease than many medical professionals had thought Nearly three-quarters of the children, admitted for a variety of problems, had an underlying genetic disorder or susceptibility Specifically, 35 percent had clearly genetic conditions (the first two entries in table 1.1); 36.5 percent had an underlying condition with a genetic predisposition, such as asthma, cancer, or type diabetes mellitus; and the rest were hospitalized for an injury or had no underlying disease K E Y C O N C E P T S Genetics investigates inherited traits and their variations Genes, composed of DNA, are the units of inheritance, and they specify particular proteins Not all DNA encodes protein A genome is the complete genetic instructions for an organism Human genome information will personalize medicine and predict future illness 1.2 From Genes to Genomes Genetics is all about the transmission of information at several levels (figure 1.2) At the molecular level, DNA comprises genes, which are part of chromosomes Each of our trillions of cells contains two sets of chromosomes, each set a copy of the genome Cells interact and aggregate into t a b l e 1.1 Effects of Genes on Health Type of Disorder or Association Example Chapter Single gene (Mendelian) Chromosomal disorder Complex (multifactorial) disorder Cancer (somatic mutation) Single nucleotide polymorphisms (SNPs) Cystic fibrosis Down syndrome Diabetes mellitus Breast cancer Associated with various conditions in different populations 4, 12 3, 7, 17 7, 8, 22 Lewis: Human Genetics Concepts and Applications, Fifth Edition I Introduction © The McGraw−Hill Companies, 2003 Overview of Genetics Gene DNA Cell Nucleus Genome (karyotype) Chromosome Population Individual Family (pedigree) Mother Father figure 1.2 Genetics can be considered at several levels Triplets Chapter One Overview of Genetics Lewis: Human Genetics Concepts and Applications, Fifth Edition Carrier—Cont of hemophilia, 267 of hemophilia A, 128 of Lesch-Nyhan syndrome, 128 of phenylketonuria, 289 of sickle cell disease, 10, 286–89, 288f of Tay-Sachs disease, 268, 289 Carrier frequency, 267 Carrier protein, 28 Carrier screening, 402t Cartilage-hair hypoplasia, 281, 281t Case-control study, 365 Caspase, 35–36, 36f Caste system, in India, 316 Cat American curl, 292, 292f artificial selection in, 292 chromosomes of, 306f, 306t coat color in, 128, 128f, 292, 311, 311f multitoed, 292f Cataplexy, 158 Cataract, 249 Cat dander, 338 Cat eye syndrome, 258 Cattle cloned calf, 71f horn development in, 129 milk yield in, 129 transgenic, 382t Cave art, 304 CCR5 receptor, 212, 284, 334–36, 335f CD4 receptor, 332, 334, 335f CD8 receptor, 332 CD antigen, 332 cDNA See Complementary DNA Cell(s), 6–7 chemical constituents of, 21 components of, 20–32 organelles in, 21–26, 22f specialized, 20, 20f, 32, 38–40, 39f Cell-cell interaction, 36–38 Cell cycle, 32–35, 32f control of, 33–35, 34f, 228–29 loss in cancer, 353, 353f synchronization of, 70f Cell death, 32–36 Cell differentiation, 38–40, 39f Cell division, 29, 32–36, 32f in cancer cells, 354t internal clock, 33–35, 69 Cell-mediated immunity, 327–28f, 328t, 330–33, 333f boosting with cytokines, 341 Cell membrane, 21, 22f, 26–29, 27f blebs, 36, 36f red blood cell, 31, 31f Cell number, 32, 32f Cell shape, 28 Cell surface, 324–27 blood groups See Blood type human leukocyte antigen, 326–27, 326f Cellular adhesion, 28, 37–38, 38f Cellular adhesion factor, 149, 150f Cellular adhesion molecule (CAM), 37–38, 38f Cellular digestion, 25–26, 25f Centimorgan, 108 Central dogma, 190, 190f Centriole, 22f, 33, 34–35f I-4 Index Back Matter Index Centromere, 33, 33–35f, 52, 207, 207t, 237–38, 237f, 240–41f, 241 composition of, 237 replication of, 237 Centromere-associated protein, 237 Centromere protein A, 237 Cervical cancer, 429f Cervix, 49, 49f CF See Cystic fibrosis CFTR See Cystic fibrosis transductance regulator Chaperone protein, 201f, 202 Charcot-Marie-Tooth disease, 221 Chargaff, Erwin, 174, 175t Chase, Mary, 172–74, 174f, 175t Checkpoint, in cell cycle, 33, 34f, 229, 353, 436 Cheetah, population bottleneck in, 283, 283f Chelator therapy, 214 Chemotherapy, 365, 367t Chernobyl disaster, 219 Chicken pox vaccine, 340 Chimera, 383 Chimpanzee, 7, 238–39, 301f, 306–10, 306t, 308f, 311f, 314 Chitinase, 409 Chlamydia pneumoniae, 345t Chloride channel, abnormal, 29 Chloroplast, transplastomics, 413 Chlybridization, 415t Chmielnicki massacre, 283–84 Cholera, 286, 289–90, 345, 345t Cholesterol, 120–21 blood, 139, 144t, 149, 150t Cholesterol-lowering drug, 3–4, 8, 149 Chondrodysplasia, 214t Chorion, 60–61f, 61 Chorionic villi, 59 Chorionic villus sampling, 59, 240–41, 242f, 242t Chromatid, 33, 33–35f Chromatin, 178, 179f Chromosomal mosaicism, 240–41 Chromosomal rearrangement, 236 Chromosomal sex, 119t Chromosome, 5f, 6, 8t, 24, 78 See also Meiosis; Mitosis acrocentric, 238, 240f banding patterns of, 239, 244, 306–7, 306f, 306t centromere position on, 238, 240f comparing chromosomes of different species, 306–7, 306f, 306t dicentric, 256, 257f, 258t DNA compacted into, 178, 179f gene-density spectrum of, 237 highly conserved, 306 homologous pairs, 49, 50f, 51–52, 79f isochromosome, 258, 258f isolation of human chromosomes, 444–45, 444f metacentric, 238, 240f metaphase, 33, 179f Philadelphia, 357–58, 358f physical relationship of genes on, 107–8 portrait of, 236–39, 237f ring, 258, 258t shorthand for, 245, 245t submetacentric, 238, 240f telocentric, 240f viral DNA integration into, 41 visualization of fluorescence in situ hybridization, 244–45, 245f obtaining cells for study, 240–43, 242f © The McGraw−Hill Companies, 2003 preparing cells for chromosome observation, 243–45 staining, 243–44 swelling, squashing, and untangling, 244 Chromosome abnormalities, 4t, 6, 236 abnormal structure, 252–58 causes of, 258t deletion, 252, 252f, 258t duplications, 252, 252f, 254f inversion, 252f, 256, 257f, 258t translocation See Translocation Chromosome number, 236, 244 abnormal, 246–51 Chronic beryllium disease, 230, 230f Chronic granulomatous disease, 68t, 124t, 334, 377t Chronic myelogenous leukemia, 238–39t Chronic myeloid leukemia, 354t, 357–58, 358f Chrysomella tremulae, 414 Cigarette smoking See Smoking Cilia, 29 abnormal, 30 Circadian pacemaker, 159 Citrobacter, 418 CJD See Creutzfeldt-Jakob disease Cleavage, 57–59, 58f, 59t Cleft lip, 65t, 142t, 144, 144f Cleft palate, 8t, 65t, 102 Cline, 279 Clinical depression See Major depressive disorder Clitoris, 49, 49f, 118, 132 Cloacal exstrophy, 132 Clomiphene, 428–29 Clonal deletion, 331 Clonal propagation, 415t Cloning, 70f bioethics of, 70–71 human, 70–71, 71f positional, 443, 449 reproductive, 70–71 therapeutic, 70 Cloning vector, 374 Clotting disorder, 40t, 102 Clotting factors, 13, 149–50, 150f, 150t, 413 Clubfoot, 144t Cluster-of-differentiation antigen, 332 Coat color, in cats, 128, 128f, 292, 311, 311f Cocaine, 55, 65, 161f, 162 Cockayne syndrome, 229f, 239f Codominance, 97–98, 98–99f, 103t Codon, 191, 196, 196f start, 198, 200, 200f stop, 198, 200, 201f, 221 synonymous, 198–99, 227 Coefficient of relatedness See Correlation coefficient Cohanim, 11 Cohesin, 237 Coley, William, 341 Collagen disorders of, 214–15, 214–15f, 214t structure of, 214f type X, 385 Collagen gene, 195 Collectin, 328–29, 328t Collins, Francis, 442–43, 449 Colon cancer, 67, 229, 238t, 360–64, 360f, 362t, 364f, 365t, 366f in families, 352 Colony stimulating factor, 332, 333t, 341, 377t Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Color blindness, 68t, 121–23, 122–23f, 124t Common ancestor, 198, 239, 301f, 307, 313 Comparative genomics, 451, 452f Complementary base pairing, 176–77f, 177–78, 310, 311f in replication, 182f, 183 in RNA, 191 in transcription, 193 Complementary DNA (cDNA), 191 Complementary DNA (cDNA) library, 376–77, 376f Complement system, 328–29, 328t, 330f Complete penetrance, 100 Complex trait See Multifactorial trait Concordance, 145–46, 149t Conditional mutation, 227 Cone cells, 122–23 Congenital adrenal hyperplasia, 118, 132, 402t Congenital generalized hypertrichosis, 124t, 125–26, 126f Congenital rubella syndrome, 66–67 Conjoined twins, 61–62, 62f Connective tissue, 20 Connective tissue cells, 33 Consanguinity, 84, 88f, 151, 278 Conservative replication, 178, 180f Constant region, of antibody, 330, 332f Constitutional mutation See Germline mutation Contact inhibition, 355 Contig, 443f, 445 Cooley, Thomas, 213 Copper, 23 Corn bt, 13–14, 378, 419 effect on monarch butterflies, 419, 421, 421f genetically modified, 409t, 413, 419, 419f Starlink, 411 Corneal transplant, 344 Corona radiata, 56–57, 58f Coronary artery disease, 67 Correlation coefficient, 144, 145t, 149t Correns, Karl Franz Joseph Erich, 76 Corticosteroid, 339t Cosmic rays, 219, 219t Cotton, genetically modified, 409t, 411, 414, 419, 419f Coumadin derivatives, 65t Coupling, 107, 107f, 147 Courseaux, Anouk, 308 Cowpox, 339–40 CpG island, 445 Creutzfeldt-Jakob disease (CJD), 42, 226, 279, 377 variant, 42, 203f, 226, 341 Crick, Francis, 175, 175f, 175t, 178, 190, 195–97, 199f, 446 Cri-du-chat syndrome, 252–53, 253f Crigler-Najjar syndrome, 267f, 281t, 282 Cristae, 26, 27f Critical period, 64–65, 64f Crohn disease, 38, 147–48, 238t, 239f Cro-Magnons, 301f, 304 Crop, genetically modified See Plant biotechnology Crossing over, 50f, 52, 52f, 107, 107–8f, 218, 218f inversions and, 256, 257f Crowd disease, 345 Cryoprecipitate, 13 Cryptococcosis, 345t Cryptococcus neoformans, 345t Cultural ages, 303t Cumulina (cloned mouse), 70 Index Curly hair, 82, 97 Cutshall, Cynthia, 391 CXCR4 receptor, 335 Cyanosis, 226 Cyclic AMP (cAMP), 37 Cyclin, 35 Cystic fibrosis (CF), 2–3, 3f, 4t, 8t, 12, 20, 20f, 29, 68t, 81t, 83, 83f, 138f, 202, 216t, 221 allele frequencies, 264, 293–94, 294f Burkholderia cepacia infection and, 143 carrier frequency for, 267, 267t diarrheal disease and, 287t, 289–90 gene therapy in, 395, 396f, 397–98, 398t haplotypes, 110 historical, archaeological, and linguistic correlations of, 293–94, 294f influence of other genes, 99–100 mouse model of, 382 multiple alleles for, 97, 103t preimplantation diagnosis of, 434 treatment of, 324, 324f, 377t, 394, 403 uniparental disomy and, 259, 259f Cystic fibrosis transductance regulator (CFTR), 29, 216t, 289–90 Cytochrome c, 307, 307f Cytogenetic map, 442, 442f Cytogenetics, 108, 236 Cytokine, 324, 328–30, 328t, 332, 333t, 339, 413 therapy with, 341 Cytokinesis, 32f, 33, 34–35f, 50–51f Cytoplasm, 22f, 24 Cytoplasmic donation, 433 Cytosine, 175–76, 176–77f Cytoskeleton, 27–28f, 28–32, 31f Cytotoxic T cells, 328f, 332–33, 333f, 334t, 335 D Dalton, John, 122–23 Danish Adoption Register, 145 DaSilva, Ashanti, 391 Davenport, Charles, 317 DCC gene, 364f Deafness genetic heterogeneity, 102 long-QT syndrome associated with, 29 Deatherage-Newsom, Blaine, 318, 318f Death receptor, 35–36, 36f Deford family, 83 Degeneracy, of genetic code, 198 Deinococcus radiodurans, 227 Delbrück, Max, 178 Deletion, 131, 218f, 221, 221t, 246t, 252, 252f, 258t Dementia, 156 Dendritic cells, 340, 340f Dengue, 286 Density shift experiment, 178–79, 179f Dental caries, 340t Dentin, 205 Dentinogenesis imperfecta, 205 Dentin phosphoprotein, 205, 206f Dentin sialophosphoprotein, 205, 206f Dentin sialoprotein, 205, 206f Deoxyribonucleic acid See DNA Deoxyribose, 174, 176, 176f, 190t, 191f Dependence, drug, 161, 161f Depression, 146f See also Major depressive disorder © The McGraw−Hill Companies, 2003 Dermal ridges, 139, 139f Dermatoglyphics, 139 DES See Diethylstilbestrol Detoxification, 26, 26f Deuteranopia, 123 Development, 36, 38–40, 39f homeobox genes in, 307–10 maturation and aging, 67–69 prenatal See Prenatal development sexual, 116–20 DeVries, Hugo, 76 DHT See Dihydrotestosterone Diabetes insipidus, 68t, 124t Diabetes mellitus, 4t, 8t, 133, 138f, 152, 239f, 396, 396f famine survival and, 290 type I, 238t, 337, 337t, 377, 377t infection and, 143 type II, 2, 3f, 67, 290 Diaminoanisole, 219t Diaminotoluene, 219t Diarrheal disease, cystic fibrosis and, 287t, 289–90 Diastrophic dysplasia, 239f Dicentric chromosome, 256, 257f, 258t Dicot, transgenesis of, 412 Dideoxyribonucleotide, 446–47, 447f Diet-cancer associations, 364–66 Diethylstilbestrol (DES), 64f, 65t Differentiation, 6–7 DiGeorge syndrome, 238t, 239f, 310 Digestion, cellular, 25–26, 25f Dihybrid cross, 85–87, 86f, 106f Dihydrotestosterone (DHT), 117, 118f Dimples, 82f Dinucleotide repeats, 195 Diphenylhydantoin, 65t Diphtheria, 286, 286f Diplococcus pneumoniae, 172, 173f Diploid, 49, 50f Directional gene flow, 278 Discontinuous replication, 183 Disease gene map, 239f Dispersive replication, 178, 180f Distal symphalangism, 83, 89, 89f Distorted tunes test, 145 Dizygotic twins, 59, 62, 145–47 DNA, 2, 6, 8t, 21, 24 ancient, 11, 184t, 311–12, 312f antiparallelism in, 177, 177f bacterial, 172f in chromosome, 4, 178, 179f coding strand of, 190, 191f, 194, 194f, 205 compared to RNA, 190–91, 190t, 191f comparing sequences in different species, 310–12 complementary See Complementary DNA double helix, 175, 175–77f, 177–78 functions of, 172 genomic, 376 junk, 195 methylation of, 129 minisatellite, 219, 228–29 of mitochondria, 26, 71, 103–5, 104f, 104t, 181, 227, 279–80 as molecular clock, 313–16, 315f mutations in See Mutation noncoding, 206–7, 207t palindromic, 217, 218f, 374 polymorphisms in, proof that it is genetic material, 172–74, 173–74f Index I-5 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter DNA—Cont recombinant See Recombinant DNA technology repeated sequences in, 195, 207, 207t, 217–18, 270, 272 replication of See Replication silenced, 129 with sticky ends, 374, 374–75f, 376 structure of, 176–78, 176–77f, 191f deciphering of, 174–75, 175f sugar-phosphate backbone of, 176f, 177 telomeric, 34 template strand of, 190, 191f, 193–94, 194f, 205 transcription of See Transcription x-ray diffraction pattern of, 175, 175f DNA-binding protein, 182f, 183 DNA chip See DNA microarray DNA damage checkpoint, 33, 34f DNA fingerprinting, 268–74, 268f in agriculture, 11 forensic investigations, 269–70, 271f, 272–74, 273f identification of human remains, 181, 181f World Trade Center victims, 272–74, 274f identification of individuals, 11, 269 population statistics to interpret, 269–72, 272–73f procedure for, 271f DNA fragment, polyacrylamide gel electrophoresis of, 269, 269f DNA hybridization, 310, 311f DNA microarray, 2–3, 3f, 6, 14, 87, 150 for cancer diagnosis, 367 in cancer research, 352 development of, 448 DNA polymerase, 182f, 183, 183t proofreading by, 183 Taq polymerase, 185–86 DNA primer, 185–86 DNA probe, 240, 244, 376 DNA repair, 33, 227–31, 238t in cancer cells, 353, 356, 356t disorders of, 228–31, 229f, 229t excision repair, 227–29, 228–29f, 229t mismatch repair, 228–29, 228f, 229t DNase, 173f, 377t DNA sequencing, Sanger method of, 446–47, 447f DNA virus, 41 Dog artificial selection in, 292 Mexican hairless, 96, 96f narcolepsy in, 159 Dolly (cloned sheep), 70, 269 Domain(s) of life, 20–21, 451 Domain of protein, 205 Dominant trait, 7, 8t, 78–79 autosomal, 81–83, 81f, 81t, 83t, 89, 89f codominance, 97–98, 98–99f, 103t Hardy-Weinberg equilibrium for alleles, 264–66, 265t, 266f incomplete dominance, 97–98, 98f, 103t meaning of dominance, 84 X-linked, 124–25t, 125–26, 125–26f Dopamine, 157, 166–67, 166t Dopamine receptor, 157, 161–62, 164f, 166t Dopamine transporter, 166, 166t Double helix, 175, 175–77f, 177–78 Down, Sir John Langdon, 248 Down syndrome, 4t, 9, 139, 160–61, 236, 236f, 238, 243–45, 245f, 245t, 248–49, 248t mosaic, 248 I-6 Index Index risk of, 10, 10f translocation, 247–48, 254, 255f DPC4 gene, 362t Drosophila melanogaster See Fruit fly Drug(s) produced using recombinant DNA technology, 377–78, 377t, 384 production in transgenic plants, 413–14 teratogenic, 65, 65t Drug addiction, 2, 3f, 156, 157t, 161–63, 161–62f, 166t Drug development, 14–15 Drug resistance, 335 to AIDS drugs, 290–91, 290f Dryopithecus, 300, 300f Duchenne muscular dystrophy, 8t, 20f, 48, 68t, 124t, 195, 216–17t, 221, 382, 396, 403 Duffy blood group, 108 Dulbecco, Renato, 448 Dunkers, 281, 281t Duplication, 221t, 246t, 252, 252f, 254f tandem, 221 Dust mite allergy, 338 Dwarfism, 68t, 238t, 377, 396f Dynein, 29–30 Dysautonomia, 283t Dyslexia, 8t Dystrophic epidermolysis bullosa, 214t Dystrophin, 20f, 216t, 220–21, 396, 396f E Earle, Pliny, 87 Eating disorder, 151, 157t, 158, 158f, 166t Ebola virus, 40–41, 41f Ecology, concerns about plant biotechnology, 418–19 Economics, concerns about plant biotechnology, 418–19 EcoRI, 374f Ectoderm, 59, 60f Ectopic pregnancy, 429, 429f Edward syndrome See Trisomy 18 Ehlers-Danlos syndrome, 214t, 215, 215f, 220 Ehrlich, Paul, 341 Ejaculation, 48 Ejaculatory duct, 118f Electroporation, 379, 380t, 383, 398, 412 Elementen, 76, 78 Elliptocytosis, 108, 108f Ellis-van Creveld syndrome, 281t, 282f ELSI program, 448 Embryo, 58f, 59, 60f, 130 development of, 59, 60f, 62–64, 62f preimplantation, 433–35, 434f research on “spare” embryos, 435 Embryo adoption, 433 Embryonic induction, 62 Embryonic stem cells, 70, 383, 435 Empiric risk, 10, 142–43, 142t, 149t Endoderm, 59, 60f Endometriosis, 427t, 429, 429f Endometrium, 58f Endoplasmic reticulum (ER), 24–25, 27t rough, 22f, 24–25, 24f smooth, 22f, 24f, 25 Endorphin, 162 Endostatin, 367 Endothelium, site of gene therapy, 396, 396f © The McGraw−Hill Companies, 2003 Energy production, in mitochondria, 26, 27f Enkephalin, 162 Enterococcus faecalis, 345t Entry inhibitor, 335–36 Environment/environmental effect on Alzheimer disease, 10 on body weight, 151–52 cancer and, 360, 360f on gene expression, 9, 71, 71f on illness, 143 on IQ score, 160 multifactorial traits, 137–52 release of genetically modified organisms into, 417–18, 417f on schizophrenia, 165, 165t Enzyme, 21, 176, 204f defects in genetic disorders, 23 extremozyme, 185 lysosomal, 25, 25f peroxisomal, 26, 26f Eosinophils, 339 Epidemic, 345 Epidermal growth factor, 35, 205, 377t Epidermis, 31, 31f Epidermolysis bullosa, 31, 31f, 214t Epididymis, 48, 48f, 118f Epigenesis, 70, 129 Epistasis, 98–99, 99f, 103t, 144f, 145 Epithelium, 20 Epitope, 330 EPO See Erythropoietin Epstein-Barr virus, 357 Equational division See Meiosis II ER See Endoplasmic reticulum erb-B gene, 362t Erythrocytosis, benign, 384 Erythromycin resistance, 287 Erythropoietin (EPO), 377t, 378, 382t, 384, 384f, 401 Eskimo-Aleuts, 316 Esophageal cancer, 360, 360f, 365t EST See Expressed sequence tag Estonian genetic database, 15 Estrogen receptor, 367 Etas of Japan, 304 Ethical issues See Bioethics Ethnic databases, 272 Euchromatin, 237, 237f Eugenics, 89, 167, 316–19, 317t Eugenics Record Office, 317, 317t Eukarya (domain), 20–21 Eukaryote, 21, 21f Euploid, 246 Europeans, exploration of New World, 345 Evolution, 7, 239 concerns about plant biotechnology, 418–19 of gene in primates, 308, 308–9f human, 299–316 molecular, 305–12 Evolutionary tree, 313 Ewing sarcoma, 352 Exaptation, 308 Excision repair, 227–29, 228–29f, 229t base, 228 nucleotide, 227–28 Exon, 194–95, 195f, 205, 206f, 221 Exon shuffling, 205–6, 205f Exonuclease, 183, 183t Expanding mutation, 221t Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Expanding repeat, 222–25, 222f, 225f, 445 Explant, 416 Explosives, bioremediation of, 418 Expressed sequence tag (EST), 373, 420, 448 Expression panel, Expressivity, 99–100, 103t variable, 100 Extremophile, 185 Extremozyme, 185 Ex vivo gene therapy, 394 Eye color, 139–40, 141f, 142 F Fabry disease, 124t, 398 Facial features, 76f Factor IX, 217 Factor VIII, 13, 216t, 222, 377t, 391 in milk of transgenic sheep, 380 Factor XI, 221 Fallopian tube, 49, 49f, 56f, 58f, 116f blocked, 427t, 429, 429f Familial adenomatous polyposis (FAP), 363–64, 364f Familial Mediterranean fever, 239f Familial polyposis of colon, 67 Family, 5f, Family history, 2, 3f, Famine, survival by diabetics, 290 Fanconi anemia, 40t, 229t, 283t, 426 FAP See Familial adenomatous polyposis Fatal familial insomnia, 68t, 158, 226 Fatty acid, very-long-chain, 26 Fava beans, 226 Femaleness, 116 Female reproductive system, 48–49, 49f, 116, 116f Ferritin, 395 Fertility drug, 428–29 Fertilization, 49, 56–57, 56f, 58f, 79f in vitro, 432, 434 Fertilized ovum, 49 Fetal alcohol syndrome, 65–66, 66f Fetal cell(s), in maternal circulation, 242–43, 242f, 337 Fetal cell implant, 63 Fetal cell sorting, 242–43, 242f Fetal hemoglobin, 305, 400, 400f Fetal reduction, 432 Fetus, 63, 63f Fever, 328t, 329, 329f F1 generation See First filial generation F2 generation See Second filial generation Fibrillin, 102, 215, 216t Fibrinogen, 150t Fibroblast growth factor, 305 Fibroid, 429, 429f Fibroin gene, 385 Fibronectin, 205 Field test, release of genetically modified organisms, 417–18, 417f Fingerprint pattern, 139–40, 139f, 142, 144t Finnish people, 280 Fire blight, 412 Fire use, 300f, 303 First filial generation (F1), 79 First messenger, 37, 37f Fish, genetically modified, 419 FISH See Fluorescence in situ hybridization Fisher, Sir Ronald Aylmer, 316 Index Flemming, Walter, 243f Fluorescence-activated cell sorter, 243 Fluorescence in situ hybridization (FISH), 243–45, 243f, 245f, 253, 256f, 307 Folic acid, 143, 149, 318 Follicle cells, 48, 55–57 Follicle stimulating hormone, 377t Food See also Plant biotechnology genetically modified, 12–14, 408–22, 408f Food poisoning, 344, 345t Ford, C E., 243–44 Forensic science DNA fingerprinting, 269–70, 271f, 272–74, 273f fingerprint patterns, 139, 139f identification of human remains, 181, 181f, 184t, 402t identification of individuals, 11 mitochondrial DNA in, 105 uses of polymerase chain reaction, 184t Foré people, 42, 42f Fort Detrick (Maryland), 346 Fossils, 300–303 Founder effect, 280–82, 280–81t, 293 Fragile X mental retardation gene, 224 Fragile X mental retardation protein, 224 Fragile X syndrome, 160–61, 222, 223t, 224, 224f Frameshift mutation, 221, 221t, 222f Franklin, Rosalind, 175, 175f, 175t Fraternal twins See Dizygotic twins Freckles, 82f Free radicals, 228, 365 French Canadians, 280–81 Friedman, Jeffrey, 151 Friedreich ataxia, 223t Fruit fly genome of, 449, 452, 452f homeotic mutants in, 310 “homosexuality” in, 119, 119f linkage map of, 107 white gene of, 119 Fucosidosis, 398 Fucosyltransferase 1, 98 Fungal infection, phenylketonuria and, 289 Furylfuramide, 219t Fusion gene, 222 Fusion inhibitor, 335 Fusion protein, cancer-causing, 357–58 G “Gain of function” disorder, 84, 223 Gajdusek, Carleton, 42 Galactokinase deficiency, 279, 279f, 282 Galactosemia, 402t Gallbladder cancer, 362 Galton, Sir Francis, 160, 316, 317t Gamete, 48 formation of, 49–53 See also Meiosis Gamete intrafallopian transfer (GIFT), 432–33 Gamma-delta T cells, 333, 334t Gamma globin, 400 Gamma radiation, 220 Ganciclovir, 397, 397f Gap phase, 32, 32f Gardner, Eldon, 363 Gardner syndrome, 364 Garrod, Archibald, 101, 125, 172 © The McGraw−Hill Companies, 2003 Gastrin, 356 Gastrula, 59, 59t GATTACA (film), 15 Gaucher disease, 81t, 221–22, 283t, 377t, 396f, 398t Gelsinger, Jesse, 392–93, 392f GenBank, 443 Gender, effects on phenotype, 128–33 Gender identity, 119, 119f, 119t, 132 Gene, 6, 8t, 78–79, 176 atavistic, 126 definition of, 2, 6, 450 effect on health, 4t fusion, 222 highly conserved, 306 homeobox, 307 linked See Linkage minimum set required for life, 451, 452f symbols for, 79–80 thrifty, 151 Genealogy, 89 Gene duplication, 205, 218f, 308, 309f Gene expression, 190 See also Transcription; Translation differential, 38–40, 39f environmental effects on, 9, 71, 71f, 143 Gene family, 238, 305 Gene flow, 264 directional, 278 Gene genealogy, 292–94 Gene gun, 379, 414 Gene mapping, 109–10, 442f Gene number, 204–5, 204–6f Gene pool, 7, 8t, 264 changing, 277–94 Gene products, altering levels of, 414–15, 415f Gene sequencing, technological aspects of, 448–50, 449–50f Gene targeting, 382–85, 383f healthy knockouts, 385 Gene therapy, 12, 14, 403 in adenosine deaminase deficiency, 390–91, 390f bioethical concerns about, 394t in Canavan disease, 393–94, 393f in cancer, 397–98, 398f, 398t clinical trials of, 394t in cystic fibrosis, 395, 396f, 397–98, 398t definition of, 390 gene delivery, 398–400, 398t germline, 395 in hemophilia, 12–13, 391 mechanics of, 394–401 in melanoma, 397–98, 398f in ornithine transcarbamylase deficiency, 392–93, 392f scientific concerns about, 394t in situ, 394 somatic, 395 successes and setbacks, 390–94 suicide, 397 treating the phenotype, 394–95 ex vivo, 394 in vivo, 394 Genetically modified animals, 13 Genetically modified food, 12–14 Genetically modified organisms, release into environment, 417–18, 417f Genetically modified plants See Plant biotechnology Index I-7 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Genetical Theory of Natural Selection, The (Fisher), 316 Genetic code, 190, 196, 199t deciphering of, 196–99, 198t degeneracy of, 198 nonoverlapping nature of, 197–98, 197f punctuation codons in, 198 triplet nature of, 196–97, 196–97f universality of, 198, 372f Genetic counseling, 3, 9, 90, 240, 401–3, 401f in breast cancer, 361–62, 361t nondirective, 402 prenatal, 401 quandaries and challenges, 403 services provided, 401–2, 401f for sickle cell disease, 403 Genetic database, national, 15 Genetic determinism, 9, 156 Genetic discrimination, 4, 230, 319 Genetic disorder, 11–12, 12t age of onset of, 12, 48, 67–69, 84, 100 defects in macromolecules in, 23 preimplantation genetic screening, 433–37, 434f at whole-person and cellular levels, 20f Genetic diversity, 52–53, 419 Genetic drift, 264, 280–84, 291f Genetic engineering, 371–85 See also Gene targeting; Recombinant DNA technology safety concerns about, 13–14, 14f Genetic equity, 14–15 Genetic heterogeneity, 102, 103t Genetic load, 284 Genetic modification, 372 Genetic parent, 430 Genetic privacy, 230, 319 Genetic risk, modified, Genetics, Genetic screening, 12, 401–3 Genetic terminology, 79–80 Genetic test for beryllium sensitivity, 230, 230f for predisposition to cardiovascular disease, 150, 150f preimplantation, 12, 433–37, 434f prenatal See Prenatal test presymptomatic, 12, 402, 402t Genital warts, 341, 377t Genome, 2, 5f, 6, 8t comparing genomes, 305–6 noncoding DNA, 206–7, 207t of pathogens, 344–46 protein-encoding genes, 238 Genome project, 2, 110, 441–52 See also Human genome project information provided by, 450–52 nonhuman, 450–52 questions raised by, 450–52 Genome sequencing, 203–7, 441–52, 442–43f steps in, 448t Genomic DNA, 376 Genomic imprinting, 71, 129–33, 130–32f, 131t, 259 Genomic library, 376, 376f Genomics, 2, 8t, 147 comparative, 451, 452f plant, 420–22 Genotype, 7, 8t, 79 phenotype/genotype correlations, 97 thrifty, 290 Genotype frequency, 264 I-8 Index © The McGraw−Hill Companies, 2003 Index Genotypic diversity, 49 Genotypic ratio, 80 Gentamicin resistance, 287 George III, King of England, 100–102, 100f German measles See Rubella virus Germ layers, primary, 59, 60f, 62 Germline cancer, 354, 354f, 359 Germline gene therapy, 395 Germline mutation, 212 Germ warfare, 345–46 Gestational parent, 430 Gibbon, 300, 308, 308–9f GIFT See Gamete intrafallopian transfer GigAssembler, 449 Gleevec, 358 Glioma, 396f, 397, 397f Global warming, 286 Globin, 202f Globin gene, 212–14, 213f, 218, 385 mutations in, 225–26, 226t Glomerulonephritis, 337t Glucocerebrosidase, 377t, 396f Glucose galactose malabsorption, 239f Glucose-6-phosphate dehydrogenase deficiency, 124t, 226 malaria and, 287t, 289, 289t Glucosinolate, 366, 366f Glutamate, 166, 166t Glutaric aciduria, type I, 281t, 282 Glutathione peroxidase deficiency, 245f Glycolipid, 25 membrane, 27f, 28 Glycoprotein, 25 membrane, 27f, 28 Goat, transgenic, 380, 381f, 382t Gobea, Andrew, 391 Golden rice, 12–13, 14f, 408 Golgi apparatus, 22f, 24f, 25, 27t Gonad, 48 indifferent, 116 Gonadal sex, 119t Gonorrhea, 287, 345 Gorilla, 301f, 305–6, 306t, 308f, 310 Gout, 68t Government regulation, of plant biotechnology, 411 G0 phase, 32–33, 32f G1 phase, 32–33, 32f G2 phase, 32–33, 32f Graf, Steffi, 156, 156f Grafting, apple tree, 409, 409f Graft-versus-host disease (GVHD), 337, 343–44 Grape transgenic, 409 wine grapes, 11, 12f Graves disease, 337t Green color blindness, 123, 124t Green fluorescent protein, 385, 414 Griffith, Frederick, 172, 173f, 175t Growth factor, 35, 37, 356 Growth hormone, 396f in transgenic mice, 381–82 Growth retardation, 65t Guanine, 175–76, 176–77f Guevedoces, 118 Guillain-Barré syndrome, 344 g value, 160 GVHD See Graft-versus-host disease Gypsies, 279, 279f, 282 H HAC See Human artificial chromosome Haemophilus influenzae, 345t genome sequencing, 449 Hair color of, 9, 82, 139, 212, 212f curly, 82, 97 white forelock, 311, 311f Hair follicle, 40, 125–26, 126f Hairiness, 305 Hairy cell leukemia, 377t Hairy ears, 120 Haldane, J B S., 178 Hamer, Dean, 119 Hamerton, J L., 243–44 Hancock family, 324, 324f H antigen, 98–99, 99f Haploid, 49, 50f Haplotype, 110, 110f, 147 Happy puppet syndrome See Angelman syndrome Hardy, Godfrey Harold, 264 Hardy-Weinberg equation, 265, 265t, 267, 272, 273f Hardy-Weinberg equilibrium, 264–66, 265t, 266f applications of, 267–68 Hartsoeker, Niklass, 54f Haw River syndrome, 223t Hay fever, 338 HDL See High-density lipoprotein Head and neck cancer, 362t, 365t Health care, 11–12 Hearing loss, 65t, 103t Heart disease See Cardiovascular disease Heart muscle cell, 38 Heart transplant, 344 Heavy chain, 330, 332f Height, 139–40, 140f, 142, 144, 144t HeLa cells, 354 Helicase, 182–83, 182f, 183t, 229t Helicobacter pylori, 345t Helix-turn-helix motif, 193 Helper T cells, 326–27f, 331f, 332–36, 334t, 335–36f, 339, 390 Hematopoietic stem cell, 40 Hemings, Sally, 11 Hemizygote, 120 Hemochromatosis, 8t, 68t, 81t, 100, 395 Hemodialysis, 384 Hemoglobin, 202f, 382t fetal, 305, 400, 400f sickle cell See Sickle cell disease structure of, 212–13, 213f Hemoglobin C, 226, 226t Hemoglobin Chesapeake, 226t Hemoglobin Constant Spring, 226t Hemoglobin Grady, 226t Hemoglobin Leiden, 226t Hemoglobin M, 226 Hemoglobin McKees Rock, 226t Hemoglobin Wayne, 226t Hemolytic anemia, 226, 245f, 336, 337t Hemophilia, 8t, 13, 68t, 138f, 335, 377t, 394, 396, 396f carriers of, 267 in European royal families, 87 gene therapy in, 12–13 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Hemophilia A, 121–23, 121f, 124t, 128, 216–17t, 222, 380 gene therapy in, 391 in royal families, 121f, 122 Hemophilia B, 124t, 217, 217t Henrich, Christy, 158, 158f Hensel twins, 61–62, 62f Heparin, 338 Hepatitis B vaccine, 340, 340t Hepatitis B virus, 360 infection in pregnancy, 67 Hepatitis virus, 357 Her-2/neu gene, 358, 362t, 367, 367t Herbicide resistance, 412t, 413, 413f Herbicide-resistant plant, 411, 418–19 Herceptin, 341, 358, 367t Hereditary Genius (Galton), 160 Hereditary nonpolyposis colon cancer, 229, 229t Hereditary persistence of fetal hemoglobin, 400 Hereditary spherocytosis, 31–32, 31f Heritability, 144–45, 144f, 144t, 149t broad, 145 of cancer, 355 narrow, 145 Herpesvirus infection in pregnancy, 67 vector in gene therapy, 398t Hershey, Alfred, 172–74, 174f, 175t Heterochromatin, 237, 237f Heterocyclic aromatic amine, 366, 366f Heterogametic sex, 116, 117f Heteroplasmy, 105, 105f, 181, 433 Heterozygote, 79–80, 97 balanced polymorphism, 218, 286–91, 287t manifesting, 128 Heterozygous advantage, 286 Hexoseaminidase A, 289 HGPRT deficiency, 23 High-density lipoprotein (HDL), 150, 150t Hill People of New Guinea, 304 Histamine, 329, 338, 338f Histone, 178, 179f, 225 HIV, 41, 41f mutation in, 335 replication of, 336f tat gene of, 343 transmission to fetus, 66 HIV infection, 334–36, 335–36f detection of HIV in blood, 183 evolution of HIV, 285–86, 285f in hemophiliacs, 13 HIV binding to helper T cell, 335f long term nonprogressors, 336 resistance to, 212, 278, 284, 335–36 stages of, 285–86, 285f treatment of, 286, 335, 343 resistance to AIDS drugs, 290–91, 290f, 335 tuberculosis and, 285 HLA See Human leukocyte antigen hMLH1 gene, 362t hMSH2 gene, 362t Homeobox, 310 Homeobox gene, 307 Homeobox protein, 307–8, 308f Homeodomain, 310 Home pregnancy test, 341 Hominid, 300f, 301 Hominoid, 300–301 © The McGraw−Hill Companies, 2003 Index Homo, 301, 303–4, 303f Homocysteine, 150, 150f, 150t Homocystinuria, 238t, 281t, 402t Homo erectus, 300–301f, 303, 303f, 315 Homogametic sex, 116, 117f Homogentisic acid oxidase, 101f Homo habilis, 301f, 303 Homologous chromosomes, 49, 50f, 51–52, 79f Homologous recombination, 382 Homo sapiens, 300, 301f, 303 Homosexuality, 119, 119f Homozygote, 79–80 Homunculus, 54f Hood, Leroy, 447 Hopi Indians, albinism among, 278 Hormone, 35, 204f Horse, hyperkalemic periodic paralysis in, 29 Hot spot, mutational, 217–18 Hot springs, 185 Housman, David, 445 HOX gene See Homeobox gene hPMS1 gene, 362t hPMS2 gene, 362t Human artificial chromosome (HAC), 241, 241f Human chorionic gonadotropin, 59, 240, 377t, 432 Human cloning, 70–71, 71f Human evolution, 299–316 Human genome, 2, 6–7 protein-encoding genes, 195, 203–5 reconciling gene and protein number in, 204–5, 204–6f Human genome project, 4, 195, 442–52 beginning of, 448 ELSI program of, 448 genome sequencing, 203–7, 442–46, 442–43f impact of information on daily life, 452 technological aspects of, 448–50, 449–50f timeline of, 446 Human genome sequence, 203–7 Human growth hormone, 377, 377t, 382t, 384 Human immunodeficiency virus See HIV Human leukocyte antigen (HLA), 326–27, 326f class I, 327 class II, 327 disease associations, 327 HLA-B7, 398, 398f HLA-B27, 327 HLA typing, 327 matching for transplantation, 343 Human origins, 300–305, 300–304f Human papillomavirus, 358 Human remains, identification of, 11, 105, 181, 181f, 184t, 402t World Trade Center victims, 272–74, 274f Humoral immunity, 327–28f, 328t, 330–32, 331–32f, 332t boosting with monoclonal antibodies, 341, 342f Humphrey, Hubert, 360–61 Humulin, 377 Hungerford, David, 357 Hunter-gatherer lifestyle, 301, 304 Hunter syndrome, 124t Huntingtin, 193, 216t, 222, 381, 445 Huntington disease, 8t, 12, 67, 68t, 81t, 84, 89, 96, 156, 193, 216–17t, 222, 223t, 396f, 397 genomic imprinting and, 130 mouse model of, 381 search for HD gene, 444–45, 444–45f Hutchinson-Gilford syndrome, 69 Hybridoma, 341, 342f Hydatidiform mole, 130, 131t Hydrocephalus, 318 Hydrogen bonds, in DNA, 176–77f, 177 Hydrops fetalis, 326 21-Hydroxylase deficiency, 132 Hydroxyurea therapy, 400–401, 400f Hyperacute rejection reaction, 342–44, 347 Hypercholesterolemia, familial, 8, 23, 68t, 81t, 97, 98f, 100, 103t, 149, 216t, 221, 222f, 396f, 397, 403 Hyperkalemic periodic paralysis, 29 Hyperlipoproteinemia, type I, 150 Hypertension, 8t, 67, 149–50 salt resistant, 238t Hypertrophic cardiomyopathy, familial, 68t, 81t Hypoceruloplasminemia, 245f Hypomania, 163 Hypophosphatemia, 124t Hypothyroidism, congenital, 402t I Icelandic genetic database, 15 Ice Man, 304, 304f Ice-minus bacteria, 417 Ichthyosis, 120–21, 120f, 124t ICSI See Intracytoplasmic sperm injection Identical twins See Monozygotic twins Ideogram, 245, 245f Idiotype, 330 Ig See Immunoglobulin Immune deficiency, 324 inherited, 40t, 334 Immune response adaptive, 327, 328t, 329–33 innate, 327–29, 328t interactions of innate and acquired responses, 333 primary, 330 secondary, 330, 339 Immune system altering immune function, 339–44 cells of, 327f, 334t Immunity abnormal, 334–39 cell-mediated, 327–28f, 328t, 330–33, 333f genetics of, 323–47 genomic view of, 344–46 humoral, 327–28f, 328t, 330–32, 331–32f, 332t Immunoglobulin, 204f Immunoglobulin A (IgA), 332t, 428 Immunoglobulin D (IgD), 332t Immunoglobulin E (IgE), 332t, 338–39 Immunoglobulin G (IgG), 332t Immunoglobulin M (IgM), 332t Immunosuppressive drug, 343–44 Immunotherapy, 341, 341t, 342f Implantation, 57–59, 58f Imprinting, genomic See Genomic imprinting Imprinting center, 133 Inborn error of metabolism, 26, 40t, 84, 97, 101, 101f Incas, 345 Incidence, 142 Incomplete dominance, 97–98, 98f, 103t Incomplete penetrance, 100 Incontinentia pigmenti, 124t, 125, 125f, 127–28 Independent assortment, 52, 52f, 85–87, 85–86f Index I-9 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Indifferent gonad, 116 Indigo, 377–78, 378f Individual, 5f, Induced mutation, 218–19 Infectious disease phenocopies caused by, 102, 103t resurgence of, 286 Infertility, 427–30, 427t female, 427t, 428–30, 429f male, 117, 221, 251, 253, 427–30, 427–28t, 436 Infertility test, 430 Inflammation, 37–38, 328, 328t, 329f Influenza, in pregnancy, 165 Influenza vaccine, 217, 340t Ingram, V M., 212–13 Inhalation anthrax, 346 Inheritance, modes of, 80–84 Inherited predisposition, 402t Initiation complex, 200 Innate immune response, 327–39, 328t Inner cell mass, 58f, 59, 435 Inner membrane, of mitochondria, 26, 27f Insect(s) insecticide-resistant, 419 preserved in amber, 311 Insect resistance, 414 Insertion, 221, 221t In situ gene therapy, 394 In situ hybridization, 244 Insulin, 203 genetically engineered, 377, 377t Integrin, 37–38, 38f, 398 Intelligence, 9, 144t, 145, 160–61, 160f, 160t, 166t definitions of, 160 heritability of, 160, 160t Intelligence quotient (IQ), 160, 160f Intelligence test, 160 Interchromosomal effect, 251 Interferon, 329, 332, 333t, 341, 377t, 378 Interleukin, 327f, 329, 332, 333t, 336 Interleukin-2, 341, 377t Intermediate filament, 28–31, 28f, 31f International travel, 345 Interphase, 32–33, 32f Intersex, 132 Interstitial cells, 117, 118f Intracytoplasmic sperm injection (ICSI), 432, 432f, 436 Intrauterine growth retardation (IUGR), 67 Intron, 104, 194–95, 195f, 205, 206f, 207t, 220–21, 308, 309f Inuit people, 152 Invasiveness, of cancer cells, 355 Inversion, 246t, 252f, 256, 257f, 258t in cancer cells, 357 paracentric, 256, 257f pericentric, 256, 257f In vitro fertilization (IVF), 432 with preimplantation diagnosis, 434 In vivo gene therapy, 394 Ion channel, 28, 204f faulty channels, 29 Ionizing radiation, 220 IQ See Intelligence quotient Irish potato famine, 422 Iron overload, 395 Ishihara’s test, 123f Isochromosome, 258, 258f I-10 Index Index Isograft, 342, 343f Isotretinoin, 64f, 65t, 66 IUGR See Intrauterine growth retardation IVF See In vitro fertilization J Jacob, Franỗois, 192 Jacobs, Patricia, 251 Jacobsen syndrome, 223t Jacobs syndrome, 245t, 250t, 251 Jefferson, Thomas, 11, 141–42 Jeffreys, Sir Alec, 269 Jehovah’s Witnesses, 384 Jenner, Edward, 339–40, 340f Jewish disease screen, 12 Johanson, Donald, 302f Jones, Ronald, 11 Jumping Frenchmen of Maine syndrome, 82 Junk DNA, 195 K Kaposi’s sarcoma, 357 Kartagener syndrome, 30 Karyotype, 5f, 6, 8t, 238–39, 243f in Down syndrome, 236f fetal, 240–43, 242f spectral, 245 Kent, James, 449 Kenyanthropus platyops, 301 Keratin, 31f, 191, 305, 307 Kets, 316 Kidney cancer, 239, 245f, 362t, 377t Kidney cells, 26 Kidney transplant, 342, 344 Kinase, 35 Kinetochore, 237 Klinefelter syndrome, 244, 245t, 250–52, 250t, 435 Knockin, 382–85 Knockout, 382–85, 383f, 450 normal healthy, 385 Knudson, Alfred, 359 Koch, Robert, 284 Köhler, George, 341 Krings, Matthias, 313 Kuru, 42, 42f, 341 L Labia majora, 49f Labia minora, 49f Lacks, Henrietta, 354 Lac operon, 192–93 Lactase, 23 Lactoferrin, 382t Lactose intolerance, 23, 81t lacZ gene, 376 Laetoli footprints, 301 Lake Maracaibo, Venezuela, 444 Land mine, detection of, 418 Landsteiner, Karl, 324 Language skills, 146 Late blight, 422 Lauric oil, 418 Leakey, Mary, 301 © The McGraw−Hill Companies, 2003 Leber’s hereditary optic neuropathy (LHON), 104–5 Lee, Pearl, 213 Leigh syndrome, 105 Lemba population, 11 Leptin, 151, 151f, 152t, 158, 166t Leptin receptor, 151, 152t Leptin transporter, 152t, 166t Lesbian, 119 Lesch-Nyhan syndrome, 23, 124t, 128, 434 Lethal allele, 96, 96f, 103t Leucine zipper, 193 Leukemia, 40t, 240, 310 acute myeloblastic, 354t acute myelogenous, 238t acute promyelocytic, 358 acute T cell, 357 chronic myelogenous, 238–39t chronic myeloid, 354t, 357–58, 358f hairy cell, 377t Leukocyte adhesion, 150t Leukocyte-adhesion deficiency, 37 Leukocyte trafficking, 37 Levan, Albert, 243–44 Levene, Phoebus, 174, 175t Lewis antigen, 326 LHON See Leber’s hereditary optic neuropathy Li-Fraumeni family cancer syndrome, 360–61 Ligand, 28 Ligase, 182f, 183, 183t, 229t Ligase detection reaction, 185 Light chain, 330, 332f Lignin, 414 Limb-girdle muscle dystrophy, 281t Limbic system, 161–62, 161f LINE See Long interspersed element Linguistic clues, to human migrations, 279–80 Linkage, 106–10 in humans, 108–9, 108–9f in pea plants, 106–7, 106f Linkage analysis, 147 Linkage disequilibrium, 109, 147 Linkage map, 107–9, 442–43, 442f for Y chromosome, 116–17, 117f Lipid, 21 defects in genetic disorders, 23 Lipoprotein, 149 Lipoprotein lipase, 150, 150t Liposome, for gene delivery, 379, 380f, 380t, 398 Lissencephaly, 68t Listeria, 345t Lithium, 65t Liver, site of gene therapy, 396–97, 396f Liver cancer, 357, 360, 360f Liver cells, 25–26, 26f Liver transplant, 347 Lkb1 gene, 362t Longevity, 69, 145 Long interspersed element (LINE), 207 Long-QT syndrome, 29 Lorenzo’s Oil (film), 26 Losey, John, 421 “Loss of function” disorder, 84 Low birth weight baby, 65, 67 Low-density lipoprotein (LDL), 150, 150t Low-density lipoprotein (LDL) receptor, 139, 145, 216t, 221, 222f, 396f, 397 Luciferase, 372f Lucy (fossil), 301, 302f Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Lung, site of gene therapy, 396f, 397 Lung cancer, 245f, 354, 354t, 355f, 360, 360f, 362t, 365t Luteinizing hormone, 377t Lyme disease, 345t Lyme disease vaccine, 340t Lymphochip, 4, 352 Lymphocytes, 327 Lymphoma, 240 Burkitt, 357, 357f non-Hodgkins, 40t, 352 Lyon, Mary, 127 Lysosomal storage disease, 25–26, 84, 398 Lysosome, 22f, 25–26, 25f, 27t M McCarty, Maclyn, 172, 173f, 175t McClintock, Barbara, 207 McKusick, Victor, 82 MacLeod, Colin, 172, 173f, 175t Macroevolution, 264 Macromolecule, 21 defects in inherited diseases, 23 Macrophages, 21f, 25, 326–28, 326–28f, 334t Mad cow disease, 42, 203 Major depressive disorder, 157t, 163–64, 163f, 166t Major histocompatibility complex (MHC), 326–27, 326f Malaria, 218, 226, 226t glucose-6-phosphate dehydrogenase deficiency and, 287t, 289, 289t sickle cell disease and, 286–89, 287t, 288f Maleness, 116–17 Male pseudohermaphroditism, 118, 118f Male reproductive system, 48, 48f, 116–17, 116f, 118f Malnutrition, prenatal, 66–67 Mammary gland, 24f Mammogram, 365 Mammoth cloning of, 312 DNA of, 311–12, 312f Mandrill, 309f Manic depression See Bipolar affective disorder Manifesting heterozygote, 128 Maple syrup urine disease, 23, 81t, 281t, 282, 402t Map unit, 108 Marfan syndrome, 68t, 81t, 102, 215, 216–17t Marijuana, 162 Marker test, 110 Mast cells, 329, 334t, 338, 338f Maternal age, 426–27, 429 advanced, 240 Down syndrome and, 10, 10f, 249 Maternal circulation, fetal cells in, 242–43, 242f, 337 Maternal inheritance, 103–5, 103f Maternal serum marker test, 240 Mate selection, 278 Mating, nonrandom, 264, 278, 291f Maturation, 67–69 M cells, 340, 340f MDR1 gene, 290–91, 290f Measles vaccine, 340 Medical genetics, 317–19 Megalocornea, 124t Meiosis, 49–53, 50–52f comparison to mitosis, 51 errors in, 57, 247, 247f, 250t Index Meiosis I, 50–51f, 53–56, 53f, 85f, 247f, 248, 250t Meiosis II, 50–52f, 53, 55, 247f, 248, 250t Melanin, 101f, 127, 140–42 Melanocortin-4, 166t Melanocortin-4 receptor, 151, 152t, 158 Melanocytes, 140–41 Melanoma, 355f, 362, 396f, 397–98, 398f MELAS, 104–5 Melon, genetically modified, 409t Membrane, 21 Memory cells, 327–28f, 328t, 330, 331f Mendel, Gregor, biographical information about, 76 experiments with pea plants, 76–79, 77–78f, 80t, 85–86, 86f Mendelian Inheritance in Man, Mendelian trait, 7–9, 8t, 80–84, 81t Mendel’s laws exceptions to, 95–110 independent assortment, 52, 52f, 85–87, 85–86f law of segregation, 78–79, 79f, 80t pedigrees that display, 89–90, 89–90f Meningitis, 345t Menkes disease, 68t, 124t Mennonites, 267f, 281–82, 281t Menopause, 56 Menstrual cycle, 49, 56 irregular, 428 Mental retardation, 64 See also Eugenics in fetal alcohol syndrome, 65–66, 66f in fragile X syndrome, 224, 224f in Lesch-Nyhan syndrome, 23 mild, 160 severe, 160 Meselson, Matthew, 178, 180 Mesenchymal stem cells, 40 Mesoderm, 59, 60f Mesolithic Age, 303t Messenger RNA (mRNA), 24, 24f, 191, 192t See also Transcription 5′ cap on, 194, 195f cDNA library made from, 376–77, 376f leader sequence, 200, 200f poly A tail on, 194, 195f proofreading of, 195 RNA processing, 194–95, 195f alternate splicing, 195 in translation, 199–201, 200–201f Metacentric chromosome, 238, 240f Metachromatic leukodystrophy, 281t Metaphase meiosis I, 50f, 52, 52f, 85f meiosis II, 51f, 53 mitotic, 33, 34–35f Metaphase chromosome, 33, 179f Metastasis, 356 Methanococcus jannaschii genome, 451 Methotrexate, 65t Methylation, of DNA, 129 Mexican hairless dog, 96, 96f MHC See Major histocompatibility complex Mibridization, 415t Microbe, thermophilic, 185 Microchimerism, 337 Microcosm experiment, release of genetically modified organisms, 417 Microdeletion, 253 Microevolution, 264, 291f © The McGraw−Hill Companies, 2003 Microfilaments, 22f, 27–28f, 28–29, 31, 33 Microinjection, of DNA, 379, 380f, 380t, 383, 398, 412 Micrometastasis, 367 Micropenis, 132 Microsatellite DNA, 228–29 Microtubules, 22f, 28–31, 28f, 33 Midlife motherhood, 426 Miescher, Friedrich, 172, 175t Migraine, 8t Migration, 264, 291f, 293, 293f geographical and linguistic clues to, 279–80 historical clues to, 279, 279f of Homo, 315 Milk foreign genes expressed in, 13 secretion of milk proteins, 24, 24f transgenic pharming from, 379–82, 381–82f, 382t yield in cattle, 129 Millirem, 220 Milstein, Cesar, 341 Minerals, 21 defects in genetic disorders, 23 Minisatellite DNA, 219, 228–29 Miocene ape, 300–301 Miscarriage See Abortion, spontaneous Mismatch repair, 228–29, 228f, 229t Missense mutation, 220–21, 221t, 222f Mitochondria, 22f, 26, 27f, 27t DNA of, 26, 71, 103–5, 104f, 104t, 181, 227, 279–80 as molecular clock, 313–16, 315f Mitochondrial disorder, 26, 104–5 heteroplasmy and, 105, 105f Mitochondrial Eve, 314–15 Mitochondrial inheritance, 103–5, 103f heteroplasmy, 105, 105f Mitochondrial myopathy, 104 Mitosis, 32–33, 32f, 34f, 36 abnormal, 248 comparison to meiosis, 51t MN blood type, 281t, 326 Moa, 312f Modified genetic risk, Molecular clock, 313–16, 313–15f mitochondrial DNA as, 313–16, 315f Neanderthals, 313 Y chromosome as, 313–16, 315f Molecular evolution, 305–12 comparing chromosomes, 306–7, 306f, 306t comparing DNA sequences, 310–12 comparing genomes, 305–6 comparing protein sequences, 307–10, 307f, 310f Molecular genetics, Monarch butterfly-bt corn controversy, 419, 421, 421f Mongolians, migration to America, 316 Monoamine oxidase A, 164, 164f, 166t, 167 Monoclonal antibody, 341, 342f Monocot, transgenesis of, 412 Monod, Jacques, 192, 446 Monohybrid cross, 78, 78f, 80, 83f Monosomy, 246t, 247, 247f, 255f Monozygotic twins, 59–60, 60f, 62, 145–47 Mood disorder, 156, 157t, 163–64, 163–64f Morgan, Thomas Hunt, 107 Mormons, 89 Morphogen, 30 Morquio syndrome, 245f, 281t Morton, Holmes, 282 Morula, 57, 58f, 59t Index I-11 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Mosaic, 127f, 248 Motif, 193 Motor molecule, 28 Mouse chromosomes of, 306t gene targeting in, 382–85, 383f transgenic, 381 mRNA See Messenger RNA MTS1 gene, 362t Müllerian duct, 116, 116f Mullis, Kary, 183–85 Multifactorial trait, 4t, 8–9, 8t, 137–52 adoption studies of, 145, 147 in agriculture, 145 association studies of, 147–48, 148f, 149t empiric risk of recurrence, 142–43, 142t, 149t heritability of, 144–45, 144f, 144t, 149t methods to investigate, 142–48 twin studies of, 145–46, 146f Multigene family, 238, 305 Multiple alleles, 96–97, 103t Multiple endocrine neoplasia, 68t Multiple sclerosis, 38, 139, 341, 377t, 378 Multiregional hypothesis of human origins, 314–15 Multitoed cat, 292f Mumps vaccine, 340 Munitions dump, bioremediation of, 418 Muscle, site of gene therapy, 396, 396f Muscle cells, 20, 26, 191 Muscle dysmorphia, 158 Muscular dystrophy, 20, 280 Becker, 124t, 220 Duchenne, 8t, 20f, 48, 68t, 124t, 195, 216–17t, 221, 382, 396, 403 limb-girdle, 281t Mutagen, 219t, 366, 366f accidental exposure to, 219 natural exposure to, 219–20, 219t Mutagenesis, site-directed, 219 Mutant, 79, 212 Mutant selection, 411, 415t Mutation, 6, 8t, 23, 79, 236, 264, 291f allele frequency and, 284 in cancer, 356, 356t conditional, 227 constitutional See Mutation, germline definition of, 212 deletion See Deletion effect on proteins, 212–15, 216t evolution of gene in primates, 308 expanding, 221t, 222–25, 222f, 225f, 445 factors that lessen effects of, 227 frameshift, 221, 221t, 222f germline, 212 induced, 218–19 insertion See Insertion missense, 220–21, 221t, 222f molecular evolution, 305–12 nonsense, 221, 221t, 222f point, 220–21 position in gene, 225–26 somatic, 4t, 71, 212, 354, 354f, 359 spontaneous, 216–18, 217f types of, 220–25, 221t in viruses, 217 Mutational hot spot, 217–18 Mutation rate, 284, 313–14 spontaneous, 216–17, 217t I-12 Index © The McGraw−Hill Companies, 2003 Index Myasthenia gravis, 337t Mycobacterium tuberculosis See Tuberculosis myc gene, 362t Mycoplasma genitalium genome, 451, 452t Myelin, 162f, 163, 166t, 393–94, 393f myl gene, 358 Myoglobin, 203f Myosin, 191 Myotonic dystrophy, 81t, 222–25, 223f, 223t, 225f, 239f, 445 N Nadene people, 316 Nahon, Jean-Louis, 308 Nail-patella syndrome, 108–9, 109f Nama tribe of South Africa, 279 Narcolepsy, 158 Narcolepsy with cataplexy, 158 Narrow heritability, 145 Nash family, 426, 426f Native Americans diseases from European explorers, 345 origin of, 315–16, 315f Natural-resistance-associated macrophage protein 1, 324 Natural selection, 264, 284–91, 291f Nature-versus-nurture controversy, 69, 145–47 Naura (Western Samoa) people, 151 Naylor, Ashley Elizabeth, 252, 252f N-CAM See Neural cellular adhesion molecule Neanderthals, 301f, 303–4, 313 Negative eugenics, 316 Neisseria meningitidis, 345t NEMO gene, 125 Neocentromere, 237, 241 Neolithic Age, 303t Nervous tissue, 20 site of gene therapy, 397 Neural cellular adhesion molecule (N-CAM), 161, 166t Neural tube, 62–63 Neural tube defect (NTD), 8t, 63, 142–43, 318, 318f Neuroblastoma, 40t, 352 Neurofibrillary tangle, 69 Neurofibromatosis, 8t, 205 type 1, 37, 81t, 216, 216–17t, 383–84, 383f type 2, 239f Neurofibromin, 205, 206f, 216t, 384 Neuron, 156 Neuropeptide Y, 151, 152t, 158, 166t Neurotransmitter, 156, 161f, 162 Neutrophils, 328 Newborn, HIV-positive, 66 Newborn screening, 401, 402t, 403 New World monkey, 308, 308–9f NF1 gene, 362t NF-kB, 125 Nicholas II, Tsar of Russia, 181, 181f Nickel-contaminated soil, bioremediation of, 418 Nicotine, 161f Niemann-Pick disease, 283t Nile region, 279–80 Nirenberg, Marshall, 196, 198 Nitrilase, 411 Nitrogenous base, 6, 174, 176, 176f tautomeric forms of, 216, 217f NOD2 gene, 147–48 Node cells, 30 Nolan triplets, 62 Nondisjunction, 247–49, 247f, 250t, 259, 436 Non-Hodgkins lymphoma, 40t, 352 Nonrandom mating, 264, 278, 291f Nonsense mutation, 221, 221t, 222f Norepinephrine, 163, 166t, 167 Norrie disease, 124t Notochord, 62 Nowell, Peter, 357 NTD See Neural tube defect Nuclear envelope, 21, 22f, 24f, 50–51f, 53 Nuclear membrane, 33, 34–35f Nuclear pore, 21, 22f, 24f Nuclear waste, 418 Nucleic acid, 21 See also DNA; RNA defects in genetic disorders, 23 of viruses, 40–41, 41f Nuclein, 172, 175t Nucleoid, 21 Nucleolar organizing region, 238 Nucleolus, 22f, 24, 33, 238 Nucleoplasm, 24 Nucleosome, 178, 179f, 225 Nucleotide, 6, 176, 176f Nucleotide excision repair, 227–28 Nucleus, 21, 22f, 24, 24f, 27t Nucleus accumbens, 161f, 162 Nutrient, excess, teratogenic effects of, 66 Nutritional value, of genetically modified plants, 413 O Oak ape, 300, 300f Obesity, 151–52, 151f, 152t Obsessive compulsive disorder, 157t Occupational teratogens, 66 Ochratoxin A, 289 Odone, Lorenzo, 26 Odorant receptor gene, 305–6 Oil spill, bioremediation of, 418 Okazaki fragments, 182f, 183 Old World monkey, 308, 308–9f Oligodendrocytes, 393–94, 393f Oligospermia, 428, 436 OMIM See Online Mendelian Inheritance in Man Oncogene, 220, 352, 356–58, 356t, 362f, 362t, 363 Online Mendelian Inheritance in Man (OMIM), 7, 80, 82 Oocyte, 48–49, 56–57, 120f, 127 age of, 426 banking and donation of, 426, 429, 433, 433f development of, 49–53, 55–56, 55–56f primary, 55, 55–56f secondary, 55, 55–56f Oogenesis, 55–56, 55–56f Oogonium, 55, 55f Ooplasmic transfer, 105 Open reading frame, 195 Operon, 192–93 Opium, 162 Opsin, 122–23 Opsin gene, 122–23 Orangutan, 306, 306t, 308f, 310 Organ, 6–7, 20 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Organelle, 21–26, 22f Organogenesis, 62 Organ system, 20 Orgasm, 48–49 Origin of replication, 183, 241 Ornithine transcarbamylase deficiency, 124t, 392–93, 392f Oroticaciduria, 245f Osteoarthritis, 214t Osteogenesis imperfecta, 8t, 67, 68f, 68t, 214t, 217t Otitis media, 345t Ötzi (Ice Man), 304, 304f Ouranopithecus macedoniensis, 301 Outer membrane, of mitochondria, 26, 27f “Out of Africa” view, 314–15 Ovarian cancer, 361–62, 362t Ovary, 48, 49f, 56f, 116f Ovulation, 56, 56f, 58f, 427t, 428 Ovulation predictor test, 428 Ovum, 55–56f blighted, 56 fertilized, 49 Oxidase, 334 P p53 gene, 359–61, 360f, 362t, 363–64, 363–64f p53 protein, 228 Painter, Theophilus, 243–44 Paleolithic Age, 303t Palindrome, 217, 218f, 374 Pancreas, infection of, 143 Pancreatic cancer, 356, 362, 362t Panic disorder, 157t Paper products, from genetically modified plants, 409t, 414 PAR See Pseudoautosomal region Paracentric inversion, 256, 257f Paralysis, hyperkalemic periodic, 29 Parathyroid cancer, 357 Parental, 107, 107–8f Parental generation, 79 Parent-of-origin effect See Genomic imprinting Parkinson disease, 8, 70, 223, 396f, 397 p arm, 237f Parsimony analysis, 313, 313f Parthenogenesis, 57 Partial parthenogenote, 57, 57f Particle bombardment, 379, 380t, 398, 412 Patau syndrome, 249 translocation, 254 Patents, regarding DNA and transgenic organisms, 373, 404, 419 Paternity test, 11, 402t Pathogen, 324 genomes of, 344, 345t Pattern baldness, 48, 68t, 129, 129f Pauling, Linus, 212 Paxil, 163 PCB contamination, 418 PCP, 166 PCR See Polymerase chain reaction PDGF gene, 362t Pea plants linkage in, 106–7, 106f Mendel’s experiments with, 76–79, 77–78f, 80t, 85–86, 86f Index Pedigree analysis, 7, 8t, 87–90, 401 of autosomal dominant trait, 89, 89f, 159 of autosomal recessive trait, 89, 89f display of Mendel’s laws, 89–90, 89–90f haplotypes, 110f inconclusive, 89–90, 90f of mitochondrial inheritance, 103, 103f predictions from, 90, 90f of royal families, 87–89, 88f symbols used in, 87, 88f of X-linked dominant trait, 126f of X-linked recessive trait, 120f Pekingese, 292 Pelvic inflammatory disease, 429 Penetrance, 99–100, 103t complete, 100 incomplete, 100 Penicillamine, 23, 65t Penicillin resistance, 287 Penis, 48, 48f, 116f, 118, 118f, 132 Pennington, Robert, 347 Pepper, genetically modified, 409t Peptide bond, 200 Perforin, 332, 333f Pericentric inversion, 256, 257f period gene, 159 Periodontitis, 345t Pernicious anemia, 337t Peroxisome, 22f, 25–26, 26f, 27t Pesticide, Pesticide resistance, 412, 412t Peutz-Jeghers syndrome, 362t P-glycoprotein, resistance to AIDS drugs and, 290–91, 290f Phagocytes, 36f, 328, 329f Phagocytosis, 328, 328t Pharming, transgenic, 379–82, 381–82f, 382t Phenocopy, 102, 103t Phenotype, 7, 8t, 79 gender effects on, 128–33 mutant, 212 phenotype/genotype correlations, 97 Phenotypic frequency, 264 Phenotypic ratio, 80 Phenotypic sex, 119t Phenylalanine hydroxylase, 293 p-Phenylenediamine, 219t Phenylketonuria (PKU), 68t, 81t, 97, 402t, 403 frequency in various populations, 264, 264t fungal infection and, 289 historical, archaeological, and linguistic correlations of, 292–93, 293f spontaneous abortion and, 287t, 289 Philadelphia chromosome, 357–58, 358f Phipps, James, 339–40 Phobia, 156, 157t Phocomelia, 64–65, 102 Phosphate group, 176, 176f Phospholipid, in cell membrane, 27–28, 27f Phosphorus, in pig manure, 372, 372f Photolyase, 227 Photopigment, 122–23 Photoreactivation, 227 Physical barriers, to pathogens, 327–29, 328f, 328t Physical map, 442f Phytase, 372 Phytate, 372 Phytohemagglutinin, 244 © The McGraw−Hill Companies, 2003 Pig genetically modified manure, 372, 372f transgenic, 382t xenografts from, 347, 347f Pig cell implant, 344 Pima Indians, 152, 290 Pineapple, genetically modified, 409t Pingelapese blindness, 283 Pingelapese people, 283 Pituitary dwarfism, 68t PKU See Phenylketonuria Placenta, 37, 59, 129–30, 131t Plague, 345–46 Plains Indians, tuberculosis in, 284 Plant-based vaccine, 340–41, 340f, 340t, 413 Plant biotechnology, 12–14, 407–22 altering levels of gene products, 414–15, 415f altering plants at cellular level, 415–16, 415t, 416f altering plants at gene level, 412–15, 412t, 413–15f benefits of, 420t compared to traditional plant breeding, 409–11, 409f drug production in transgenic plants, 413–14 economic, ecological, and evolutionary concerns, 418–19 government regulation of crops, 411 impact of genomics on, 420–22 release of genetically modified organisms into environment, 417–18, 417f risks of, 408, 420t steps in, 409–11, 410f traits modified, 408t Plant breeding, traditional, 409–11, 409f Plasma cells, 327–28f, 330, 331f, 338f Plasma proteins, 109 Plasmid, 287 as cloning vector, 375–76, 375f, 375t Ti, 378, 412 vector for gene transfer, 412 Plasminogen, 205 Pleiotropy, 100–102, 100–101f, 103t Pleistocene epoch, 300 Plomin, Robert, 145–46 Pluripotent cell, 39–40, 39f PMCHL genes, 308, 309f Point mutation, 220–21 Poisson distribution, 359 Polani, P E., 250 Polar body, 55–56, 55f, 58f fertilized, 56–57 Polar body biopsy, 435–36, 435f, 436t Polio vaccine, 340, 340t Pollen, of bt corn, 421 Pollen allergy, 338, 338f Polyacrylamide gel electrophoresis, of DNA fragments, 269, 269f Polycystic kidney disease, 67, 68t, 81t, 217t, 238t, 239f Polydactyly, 9, 68t, 81t, 88f, 100, 103t, 282 Polyethylene glycol, use in gene transfer, 378–79 Polygenic trait, 138–39, 142, 384–85 Polygln diseases, 223 Poly-hydroxybutyrate, 414 Polymerase chain reaction (PCR), 183–86, 184f, 184t, 270, 272, 273f quantitative, 245 uses of, 183, 184t Polymorphism, 6–7, 8t, 268–69, 269f, 450 balanced, 218, 286–91, 287t Index I-13 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Polyp, colonic, 363 Polyploidy, 49, 246, 246f, 246t, 258t Pomato, 415 Poplar tree, genetically modified, 414 Population, 5f, 7, 264 Population bottleneck, 282–84, 282f Population genetics, 7, 264 Population statistics, interpretation of DNA fingerprint data, 269–72, 272–73f Population study, 364–65 Porcine endogenous retrovirus, 347 Porphyria, 68t Porphyria variegata, 81t, 100–102, 100f, 103t, 282 Porphyromonas gingivalis, 345t Positional cloning, 443, 449 Positive eugenics, 316 Positive selection, 331 Postanesthetic apnea, 245f Post-traumatic stress disorder, 157t Postural drainage, 20f Potassium channel, abnormal, 29 Potato functional genomic project, 420, 422 genetically modified, 409t, 411, 415 Irish potato famine, 422 Poush, James, 83 Prader-Willi syndrome, 131–33, 131f, 131t, 259 PRAD1 gene, 362t Preeclampsia, 129–30, 131t Prefrontal cortex, 161f, 162 Pregnancy See also Prenatal development ectopic, 429, 429f Rh incompatibility in, 325–26, 325f Pregnancy test, 59, 341 Preimplantation embryo, 433–35, 434f Preimplantation genetic screening, 12, 433–37, 434f Preinitiation complex, 193 Premature infant, 65, 67 Pre-mRNA, 194 Premutation, 224 Prenatal development, 56–64, 59t birth defects See Birth defect cleavage and implantation, 57–59, 58f embryo formation, 59, 60f embryonic development, 62–64, 62f, 130 evolution and, 305 fetal period, 63, 63f of multiples, 59–62, 61f of reproductive system, 116, 116f in situs inversus, 30 supportive structures, 59 X inactivation, 126–28, 127–28f Prenatal test, 4, 12, 59, 401, 402t for chromosome abnormalities, 240–43, 242f for neural tube defects, 318 for pseudohermaphroditism, 118–19 Presenilin 1, 215, 215f Presymptomatic test, 12, 402, 402t Prevalence, 152 Primaquine, 226 Primary germ layers, 59, 60f, 62 Primary immune response, 330 Primary oocyte, 55, 55–56f Primary spermatocyte, 53, 53–54f Primary structure, of protein, 202, 202f Primase, 182f, 183 Primate, evolution of gene in, 308, 308–9f Primitive streak, 62 I-14 Index © The McGraw−Hill Companies, 2003 Index Prion, 41–42, 41–42f, 203 Prion disease, 341 susceptibility to, 226 Prion protein, 41f, 42, 226 Probability, 86, 87f Procollagen, 214–15, 214f, 214t Product rule, 86–87, 90, 123, 272, 273f Proflavine, 219t Progenitor cell, 39, 39f Progeria, 68t, 69, 69f Proinsulin, 203 Prokaryote, 21, 21f Prolactin, 428 Promoter, 193, 193–94f, 207t Pronucleus, 57 Proofreading of mRNA and tRNA, 195 of replicated DNA, 183 Prophase meiosis I, 50f, 51 meiosis II, 51f, 53 mitotic, 33, 34–35f Propionicacidemia, 245f Propliopithecus, 300 ProSAP2 gene, 255 Prosimian, 308, 308f Prospective study, 365 Prostaglandin, 48 Prostate cancer, 205, 238t, 362 Prostate gland, 48, 48f, 116f, 118f Prostate specific antigen (PSA), 205, 206f, 365 Protamine, 343 Protanopia, 123 Protease, 173f Protease inhibitor, 335 Protein, 21 in cell membrane, 27f, 28 comparing protein sequences, 307–10, 307f, 310f defects in genetic disorders, 23 domains of, 205 effect of mutations on, 212–15, 216t folding of, 25, 201–3, 201–3f errors in, 202, 222–25, 222f, 225f functions of, 204f highly conserved, 306 homeobox, 307–8, 308f malfunctioning or inactive, 176 meaning of dominance and recessiveness, 84 primary structure of, 202, 202f quaternary structure of, 202, 202f secondary structure of, 202, 202f secretion of, 24–25, 24f synthesis of See Translation tertiary structure of, 202, 202f Protein-encoding genes, 203–5, 238 Protein number, 204–5, 204–6f Proteome, 21 Proteomics, 203–4, 204f, 449, 451 Proto-oncogene, 356–57 Protoplast, 378, 379f Protoplast fusion, 415, 415t Prozac, 163 PSA See Prostate specific antigen PSA-linked molecule, 205, 206f Pseudoautosomal region, 117, 117f, 126 Pseudogene, 206–7, 207t, 222, 238, 305 Pseudohermaphroditism, 118 male, 118, 118f Pseudomonas aeruginosa, 143 P site, on ribosome, 200 Psychosis, 156 5p– syndrome See Cri-du-chat syndrome Ptolemy dynasty, 88f Puberty, female, 56 Pufferfish genome, 305 Pugdog, 292 Punnett, R C., 106 Punnett square, 80–81, 80–81f, 83f, 86–87, 86–87f Purine, 176, 176–77f Pygmies of Africa, 304 Pyrimidine, 176, 176–77f, 190 Pyrimidine dimer, 227, 228f Pythagoras, 226 Q q arm, 237f 22q13.3 deletion syndrome, 255 QTL See Quantitative trait loci Quadruple repeat disorder, 224–25, 225f Quagga, 312f Quantitative PCR, 245 Quantitative trait loci (QTL), 139 Quaternary structure, of protein, 202, 202f R Rabbit, transgenic, 382f, 382t Rabies vaccine, 417 Race, definition of, 141–42 Radiation, mutagenic, 219 Radiation poisoning, 219 Radiation therapy, 365, 367t Radioactive isotope, 220 Radon, 219 Randell, Max, 393f, 395 Ransome, Joseph, 122 Rape suspect, 269–70, 271f ras gene, 362t, 364f Rat, transgenic, 382t RB gene, 359–60, 362t Reactive oxygen species, 428 Reading disability, 146f Reading frame, 197 Reagan, Ronald, 68f Receptor, 28, 204f See also specific types of receptors in signal transduction, 36–37, 37f Recessive trait, 7, 78–79 autosomal, 81t, 83–84, 83f, 84t, 89, 89f Hardy-Weinberg equilibrium for alleles, 264–66, 265t, 266f meaning of recessiveness, 84 X-linked, 120–23, 120t, 124t Reciprocal translocation, 254–55, 256f Recombinant, 107–8, 107–8f Recombinant DNA technology, 185, 372–78, 384 applications of, 377–78, 377t, 378f constructing recombinant DNA molecules, 374–76, 374–75f, 375t isolating gene of interest, 376–77 selecting recombinant DNA molecules, 376 Recombination, homologous, 382 Recombination mapping, 109, 109f Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Red blood cells See also Blood type membrane of, 31, 31f sickled See Sickle cell disease Red color blindness, 123, 124t Reduction division See Meiosis I Regeneration, of plants, 411 Regenerative medicine, 6–7, 40 Regulator, in signal transduction, 37, 37f Reimer twins, 132 Rejection reaction hyperacute, 342–43, 347 in transplantation, 342–44 Relative risk, 9–10, 10f Release factor, 201f Renin inhibitor, 377t Rennin, 377 Replacement hypothesis, of human origins, 314–15 Replication, 33, 33f, 178–83, 190f conservative, 178, 180f density shift experiment, 178–79, 179f direction of, 182f, 183 discontinuous, 183 dispersive, 178, 180f errors in, 182f, 216, 217f, 227 lagging strand, 182f leading strand, 182f PCR See Polymerase chain reaction semiconservative, 178–80, 180f steps and participants in, 180–83, 182f, 183t in thermophilic microbes, 185 Replication fork, 183 Reproductive choice, 316–17 Reproductive cloning, 70–71 Reproductive system female, 48–49, 49f, 116, 116f male, 48, 48f, 116–17, 116f, 118f prenatal, 63, 116, 116f Reproductive technology, 425–37 Repulsion, 107, 107f, 147 Restriction enzyme, 268–69, 269f, 271f, 374–75, 374–75f Restriction fragment length polymorphism (RFLP), 268–69, 269f, 444 Retinal, 122–23 Retinitis pigmentosa (RP), 102, 124t, 282 Retinoblastoma, 217t, 359–60, 359f, 382 Retinoic acid, 367 Retinoic acid receptor, 358 Retinoids, 358 Retinoschisis, 124t RET gene, 362t Retrotransposon, 308 Retrovirus, 41, 380t vector in gene therapy, 398t Rett syndrome, 124t Reunion Island residents, 99 Reuptake transporter, 162 Reverse transcriptase, 41, 41f, 336f, 376, 376f Reverse transcriptase inhibitor, 335 RFLP See Restriction fragment length polymorphism Rhabdomyosarcoma, 352 Rh blood type, 108, 108f, 280, 281t Rheumatic fever, 337 Rheumatic heart disease, 337t Rh factor, 325–26, 325f Rhizosecretion, 413–14, 414f Rh-null disease, 245f Rhodopsin, 102, 123 Index RhoGAM, 325f, 326 Ribonucleic acid See RNA Ribose, 174, 190t, 191f Ribosomal protein genes, 238 Ribosomal RNA (rRNA), 191–92, 192t Ribosomal RNA (rRNA) genes, 206–7, 207t, 238 Ribosome, 21, 22f, 24–25, 27t, 192, 192f A site on, 200 P site on, 200 subunits of, 192, 192f in translation, 199–201, 200–201f Ribozyme, 192, 194, 200 Rice genetically modified, 409t genome sequence for, 420 golden, 12–13, 14f, 408 Rickets, 68t Rickettsia prowazekii, 345t Ring chromosome, 258, 258t Risk, 401 absolute, 9–10, 10f empiric, 10, 142–43, 143t, 149t relative, 9–10, 10f statistical representation of, 9–10, 10f Risk factor, 9–10 RNA, 6, 8t, 21, 24 compared to DNA, 190–91, 190t, 191f conformations of, 191 messenger See Messenger RNA noncoding, 206–7, 207t ribosomal See Ribosomal RNA structure of, 190–92, 191f synthesis of See Transcription transfer See Transfer RNA types of, 190–92, 192t RNA polymerase, 190, 193, 193–94f RNA primer, 183 RNA processing, 194–95, 195f RNA tie club, 199, 199f RNA virus, 41 Robertsonian translocation, 253–54, 255f Rodman, Toby, 343, 343f Romanov family, 181, 181f Rough endoplasmic reticulum, 22f, 24–25, 24f Rowley, Janet, 357 Royal families hemophilia A in, 121f, 122 pedigree analysis of, 87–89, 88f porphyria variegata in, 100–102, 100f RP See Retinitis pigmentosa Rubella vaccine, 340 Rubella virus, teratogenic effects of, 66 S Saccharomyces cerevisiae genome, 451 Saint Bernard dog, 292 Salivary gland cancer, 362t San (bushman), 304 Sanger method, of DNA sequencing, 446–47, 447f Sanitaria, 285, 285f Sardinian population, 278 Satellite, chromosomal, 238 Satellite DNA, 241, 241f Scaffold, 443, 443f Scaffold protein, 178 Schizophrenia, 8t, 146f, 157t, 164–67, 165f, 165–66t, 238t © The McGraw−Hill Companies, 2003 Schneider, Linda, 104–5 Schwarz, Stefan, 252 SCID See Severe combined immune deficiency Scleroderma, 337, 337f, 337t Scrapie, 41f, 42, 203, 203f, 226 Scrotum, 48, 48f, 118f Scurvy, 66 Secondary immune response, 330, 339 Secondary oocyte, 55, 55–56f Secondary spermatocyte, 53, 53–54f Secondary structure, of protein, 202, 202f Second filial generation (F2), 79 Second messenger, 37, 37f Secretion, 24–25, 24f Secretor gene, 326 Seed artificial, 415t, 416f drug production in transgenic plants, 413–14 suicide, 419 Segregation, law of, 78–79, 79f, 80t Seizure, 23 Seizure disorder, 8t Selectin, 37, 38f Selective serotonin reuptake inhibitor (SSRI), 163, 163f Self-destructive behavior, 23 Semen, transgenic pharming from, 379–82, 381–82f, 382t Semiconservative replication, 178–80, 180f Seminal fluid, 48, 48f Seminal vesicles, 48, 48f, 118f Seminiferous tubules, 48, 48f, 54, 54f Sensitization, 339t Sequence map, 442f Sequence tagged site (STS), 443, 443f Serotonin, 119, 163–64, 163–64f, 166t, 167 Serotonin transporter, 163–64, 164f Severe combined immune deficiency (SCID), 124t, 239f, 334, 383, 390–91, 390f, 396f, 403 Sex chromosome, 6, 8t, 116–17 aneuploid, 249–51, 250t traits inherited on, 120–26 Sex determination, 63, 120f Sex-influenced trait, 129, 129f Sex-limited trait, 129 Sex reassignment surgery, 132 Sex selection, 434–35 Sexual development, 116–20, 250 Sheep, transgenic, 379–80, 382t Shelton, Anthony, 421 Short interspersed element (SINE), 207 Short tandem repeat (STR), 272 Siamese twins See Conjoined twins Sickle cell disease, 8t, 10, 20, 20f, 40t, 68t, 81t, 84, 90, 90f, 220, 226, 226t, 385, 402t genetic counseling and, 403 malaria and, 286–89, 287t, 288f mutation in beta globin gene, 212–14, 213f treatment of, 398t, 400–401, 400f Siemens, Hermann, 145 Signal transduction, 28, 36–37, 37f, 152, 162 SINE See Short interspersed element Single-celled organism, 20 Single-gene disorder, 4t, 7, 138 Single-gene inheritance, 80–84 Single nucleotide polymorphism (SNP), 4t, 6, 15, 110, 158 Single nucleotide polymorphism (SNP) analysis, 185 Index I-15 Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Single nucleotide polymorphism (SNP) mapping, 147, 148f Sinsheimer, Robert, 448 Sister chromatids, 33f, 51f Site-directed mutagenesis, 219 Situs inversus, 30, 30f Skin color of, 139–42, 141f intermediate filaments in, 31, 31f site of gene therapy, 396, 396f Skin cancer, 229, 229f, 355, 355f, 360, 364 Skin cells, 191 Slave trade, 282 Sleep, 158–59 Sleep-wake cycle, 159 Small nuclear ribonucleoprotein (snRNP), 194, 207t Small nucleolar RNA (snoRNA), 206, 207t Smallpox, 339–40, 340f, 345–46, 346f Smallpox vaccine, 340 Smallpox virus, 41 Small round blue-cell tumor, 352 Smell, sense of, 305 Smoking, 65, 354, 365t Smooth endoplasmic reticulum, 22f, 24f Snapdragon, flower color in, 97 snoRNA See Small nucleolar RNA SNP See Single nucleotide polymorphism snRNP See Small nuclear ribonucleoprotein Sodium channel, abnormal, 29 Sodium nitrite, 219t Somatic cell(s), 32, 49, 411 Somatic cell hybridization, 444–45, 444f Somatic embryo, 416, 416f Somatic gene therapy, 395 sites of, 395–98, 396–98f Somatic mutation, 4t, 71, 212, 354, 354f, 359 Somatostatin, 377t Somatotropin, 384 Somoclonal variant, 415t, 416, 416f Soybean, genetically modified, 413, 419f Spare embryo, 435–37 Specialized cells, 20, 20f, 32, 38–40, 39f Spectral karyotype, 245 Spectrin, 31–32, 31f Sperm, 48–49, 53–54f, 54, 56–57, 120f antibodies against, 427t artificial insemination, 430, 430t development of, 49–55, 53–54f with hampered mobility, 427t, 428, 428f structure of, 54, 54f Spermatid, 53f, 54, 436 Spermatocyte primary, 53, 53–54f secondary, 53, 53–54f Spermatogenesis, 53–55, 53–54f, 343, 428 Spermatogonium, 53, 53f Spermatozoa See Sperm Sperm bank, 430 Sperm cell concentrate, 428 Sperm count, 427t, 428 S phase, 32–33, 32–33f Spherocytosis, hereditary, 31–32, 31f Spidroin gene, 385 Spina bifida, 318 Spinal and bulbar muscular atrophy, 223t Spinal cord injury, 70 Spinal muscular atrophy, 239f Spindle, 33, 34–35f, 50–51f, 51–52, 237 I-16 Index Index Spindle assembly checkpoint, 33, 34f Spinocerebellar ataxia, 223t Spleen, 327, 327f Splenic cancer, 360f Spliceosome, 194–95 Spontaneous mutation, 216–18, 217f SRY gene, 63, 116–17, 117f SSRI See Selective serotonin reuptake inhibitor Stahl, Franklin, 178, 180 Stain, chromosomal, 243–44 Staphylococcus aureus, 345t Start codon, 198, 200, 200f Startle reflex, 82 Statin, 4, 8, 149 Statistics, representation of risk, 9–10, 10f Stem cells, 6, 38–40, 39f, 59, 70 bioethics of stem cell technology, 40, 70–71 hematopoietic, 40 Stent, Gunther, 178 Sterilization, forced, 317, 317t Steroid 5-alpha reductase, 239f Stickler syndrome, 214t Stillbirth, 65–66, 246f, 256 Stomach cancer, 354t, 362, 362t, 365 Stop codon, 198, 200, 201f, 221 STR See Short tandem repeat Streptococcus pneumoniae, 344, 345t Streptokinase, 378 Streptomycin resistance, 287 Stress resistance, in plants, 414–15 Stroke, 67 STS See Sequence tagged site Sturtevant, Alfred, 107–8 Subfertility, 427–30, 427t Submetacentric chromosome, 238, 240f Substantial equivalence requirement, 411 Subtelomere, 238, 239f Sucrose intolerance, 245f Sugar beet, genetically modified, 412 Sugarcane, genetically modified, 412 Sugar-phosphate backbone, 176f, 177 Suicide gene therapy, 397 Suicide seed, 419 Superovulation, 428–29, 432 Superoxide dismutase, 377t Suprachiasmatic nucleus, 159 Surfactant protein, 377t Surrogate motherhood, 426, 431–32 gestational-only, 432 Survivin, 33 Sustentacular cells, 117, 118f SV40, 358 Sweat gland, 127, 127f Sweet pea, genetically modified, 409t Synapsis, 50f, 51–52 Syndrome, 236 Synonymous codon, 198–99, 227 Synpolydactyly, 310, 310f Synteny, 307 Synthesis phase, 32, 32f Syphilis, 345t Systemic lupus erythematosus, 337t T Tabby cat, 292 Tamoxifen, 367, 367t © The McGraw−Hill Companies, 2003 Tandem duplication, 221 Taq polymerase, 185–86 TATA binding protein, 193, 193f TATA box, 193 tat gene, 343 Tau protein, 69 Tautomer, of nitrogen-containing bases, 216, 217f Tay-Sachs disease, 8t, 25–26, 68t, 81t, 84, 97, 268, 283t tuberculosis and, 287t, 289 T cell(s), 326–27, 326f, 328f, 330–33, 334t, 391 cytotoxic, 328f, 332–33, 333f, 334t, 335 defective, 334 gamma-delta, 333, 334t helper, 326–27f, 331f, 332–36, 334t, 335–36f, 339, 390 T cell receptor, 333f Teeth enamel formation, 117f genetic variants in, 82 Telocentric chromosome, 240f Telomerase, 34, 353, 353f, 367 Telomerase RNA, 207t Telomere, 34, 35f, 70, 207, 207t, 237–38, 237f, 241, 241f in cancer cells, 353, 353f Telophase meiosis I, 50f, 52 meiosis II, 51f, 53 mitotic, 33, 34–35f Teratogen, 64–67, 65t, 102 Teratoma, 57, 130 Tertiary structure, of protein, 202, 202f Testis, 48, 48f, 54f, 116f, 117–18, 118f Testosterone, 117–18, 118f, 250, 252 Testosterone receptor, 117–18 Tetanus vaccine, 340t Tetracycline, 65t Tetracycline resistance, 287 Tetrad, 52 Tetrahydrocannabinol, 162 Textiles, from genetically modified plants, 414 Thalassemia, 40t, 213–14, 217–18, 398t Thalassemia major, 213 Thalassemia minor, 214 Thalidomide, 64f, 65, 65t, 102 Therapeutic cloning, 70 Thermophilic microorganism, 185 Thrifty gene, 151 Thrifty genotype, 290 Thrill-seeking behavior, 167, 167f Thrush, 334 Thumb, ability to bend backward or forward, 82f Thymidine kinase, 397, 397f Thymine, 175–76, 176–77f, 190t, 191f Thymine dimer, 227, 228f Thymocytes, 331, 336 Thymus, 331 Thyroid cancer, 219, 352, 360f, 362t Thyroid hormone resistance, 245f Tijo, Joe-Hin, 243–44 Ti plasmid, 378, 412 Tissue, 6–7, 20 Tissue plasminogen activator (t-PA), 205, 377t, 378, 382t in milk of transgenic goats, 380, 381f TNT contamination, bioremediation of, 418 Tobacco, genetically modified, 372f, 414 Tolerance, drug, 161, 161f Lewis: Human Genetics Concepts and Applications, Fifth Edition Back Matter Tomato Flavrsavr, 414, 415f genetically modified, 409t, 412–13 Tool use, 300f, 303, 303t Tortoiseshell cat, 128, 128f Total ridge count, 139, 144t Totipotent cell, 39, 39f Toxic shock syndrome, 345t t-PA See Tissue plasminogen activator Training of the Human Plant, The (Burbank), 316 Transcription, 190–96, 190–91f elongation phase of, 193, 194f initiation of, 193, 193–94f RNA structure and types, 190–92 steps of, 193–94, 193–94f termination of, 193, 194f Transcription factor, 192–93, 193f, 204f, 356, 358, 360, 414 homeobox proteins, 310 SRY, 117 Transfer RNA (tRNA), 24, 192, 192f, 192t proofreading of, 195 in translation, 196f, 199–201, 200–201f Transfer RNA (tRNA) genes, 199, 206, 207t Transformation, microbial, 287 Transforming principle, 172, 173f Transfusion, 324–26, 384 Transgenic animal, 372–73, 378–81, 382f, 382t, 408 Transgenic organism, delivering DNA, 378–79, 379f, 380t Transgenic plant, 12–14, 373, 378, 408, 413–14, 413t transgene transfer from crops to weeds, 418–19 Transition (mutation), 220 Translation, 190, 190f, 196–203, 196f elongation phase of, 200, 201f initiation of, 200, 200f termination of, 200, 201f Translocation, 239, 246t, 253–56, 255–56f, 258t, 403 in cancer cells, 357, 357f reciprocal, 254–55, 256f Robertsonian, 253–54, 255f Translocation carrier, 254–55, 255f Transmissible spongiform encephalopathy, 41–42, 203, 203f, 226 Transmission genetics See Mendelian trait Transmitting male, 224 Transplantation, 324, 339, 342–44 HLA matching in, 327, 343 rejection reactions, 342–44 types of, 342, 343f Transplastomics, 413 Transposition, 308 Transposon, 207, 207t, 222 Trans-splicing, 205 Transversion (mutation), 220 Traveler’s diarrhea vaccine, 340t Tree in bioremediation, 418 genetically modified, 409t, 414, 417–18 Trekboers, 279 Treponema pallidum, 345t Trichothiodystrophy, 226, 228, 229f, 229t Triplet repeat disorder, 203, 222–25, 223t, 225f, 445 Triplets, 62, 146–47 Triploidy, 246, 248 Triplo-X, 250, 250t Tris, 219t Trisomy, 246t, 247, 247f, 259 © The McGraw−Hill Companies, 2003 Index Trisomy 13, 248–49, 248t Trisomy 16, 248 Trisomy 18, 248–49, 248t, 249f Trisomy 21 See Down syndrome tRNA See Transfer RNA Trophoblast, 59, 60f True breeding plant, 76, 78f Tschermak, Seysenegg, 76 Tuberculosis, 146, 345t drug-resistant, 284–86 evolution of, 284–85, 285f HIV infection and, 285 Tay-Sachs disease and, 287t, 289 Tubulin, 28–29, 28f, 33 Tumor, 352 Tumor necrosis factor, 329, 332, 333t, 336, 341 Tumor suppressor gene, 220, 352, 356, 356t, 358–62, 360f, 362t Tumor syndrome, 133 Turner, Henry, 249 Turner syndrome, 244, 245t, 249–50, 250t, 258 risk of disease in adulthood, 250, 251f Twins, 59–62, 61f conjoined, 61–62, 62f dizygotic, 59, 62, 145–47 fraternal See Twins, dizygotic identical See Twins, monozygotic monozygotic, 59–60, 60f, 62, 145–47 vanishing twin phenomenon, 62 Twins Early Development Study, 145–46 Twin study on homosexuality, 119 of multifactorial traits, 145–46, 146f “twins reared apart,” 146–47 Two-hit hypothesis of cancer, 354, 359–60, 359f Tyler family, 76f Typhoid fever, 290 Typhus, 345t Tyrosine hydroxylase, 396f Tyrosine kinase, 357–58 Tyrosinemia, 397 U Ulcerative colitis, 336, 337t Ullman, Emmerich, 347 Ulrich syndrome See Turner syndrome Ultrasound scan, of embryo or fetus, 242f, 243 Ultraviolet radiation, 227 Umbilical cord, 59 Umbilical cord blood, 391 Umbilical cord stem cells, 40, 40t, 334, 426 Uniparental disomy, 133, 259, 259f Universal blood type, 325 Universal donor, 325 Universality, of genetic code, 198, 372f Universal recipient, 325 Uracil, 190, 190t, 191f Urethra, 48, 48–49f, 118f Usher syndrome, 238t Uterus, 49, 49f, 58f, 116f V Vaccine, 339–41, 340f, 340t cancer, 367, 397 plant-based, 340–41, 340f, 340t, 413 types of, 340t Vagina, 49, 49f, 116f Vaginal adenosis, 65t Vaginal cancer, 65t Vanishing twin phenomenon, 62 Variable expressivity, 100 Variable region, of antibody, 330, 332f Vas deferens, 48, 48f, 116f, 118f Vault RNA, 207t Vector, cloning See Cloning vector Vegetables, cancer risk and, 366 Venter, J Craig, 442, 449 Ventral tegmental area, 161f, 162 Very-long-chain acyl-CoA dehydrogenase deficiency, 97 Very-long-chain fatty acid, 26 Vesicle, 24f, 25, 27t Vetter, David, 334 Vibrio cholerae, 345t Victoria, Queen of England, 87, 121f, 122 Violent behavior, 167 Virus, 40–41, 41f cancer and, 356–57 infection during pregnancy, 66–67 mutations in, 217 structure of, 40–41, 41f use in gene transfer, 380t, 398, 398t in xenografts, 347 Vitamin(s), 21 defects in genetic disorders, 23 Vitamin A, 66, 122–23, 408 Vitamin B12, 143 Vitamin C, 66 Vlax Roma gypsies (Bulgaria), 279, 279f von Willebrand disease, 68t W Waardenburg syndrome, 311, 311f Watson, James, 175, 175f, 175t, 178, 190, 199f, 448 Weight See Body weight Weinberg, Wilhelm, 264 Werner syndrome, 69, 229t Wexler, Nancy, 444 Weyers acrodental dysostosis, 281f White, Timothy, 302f White blood cells, 25, 37, 38f, 240 in semen, 428 White forelock, 311, 311f white gene, of fruit fly, 119 Whitehead, Mary Beth, 432 Widow’s peak, 82, 82f Wild type, 79 Wilkins, Maurice, 175, 175t Willard, Huntington, 241 Wilms’ tumor, 358–59 Wilson, Allan, 314 Wilson disease, 23, 68t Wine grapes, 11, 12f Wiskott-Aldrich syndrome, 124t Wobble position, 199 Wolffian duct, 116, 116f Wood products, from genetically modified trees, 414 Woods, Tiger, 141, 141f World Trade Center victims, identification of, 105, 272–74, 274f Index I-17 Lewis: Human Genetics Concepts and Applications, Fifth Edition Wright, Pat, 101 WT1 gene, 362t X X chromosome, 6, 63, 116–17, 117f, 120f abnormal number of, 249–51, 250t homosexuality markers on, 119 inactivation of, 71, 126–28, 127–28f, 250 linkage map of, 108 ring, 258 X-Y homologs, 117 Xenobiotic metabolizing enzyme, 366, 366f Xenograft, 342, 343f, 344, 347, 347f Xeroderma pigmentosum, 68t, 229, 229f, 229t X inactivation center, 126 45,X individual, 248 XIST gene, 126 Xist RNA, 207t XIST site, 258 I-18 Index Back Matter © The McGraw−Hill Companies, 2003 Index X-linked trait, 120 allele frequency for, 267 dominant, 124–25t, 125–26, 125–26f recessive, 120–23, 120, 124t X-ray diffraction pattern, of DNA, 175, 175f X-ray therapy, 220 XX male syndrome, 117 XXX cell, 127f XXXX cell, 127f XY female syndrome, 117 XYY syndrome See Jacobs syndrome Y YAC See Yeast artificial chromosome Yanomami of Brazil, 304 Y chromosome, 6, 63, 116–17, 117f, 120f deletions of, 428 genes unique to, 117 linkage map for, 116–17, 117f as molecular clock, 313–16, 315f pseudoautosomal region of, 117, 117f X-Y homologs, 117 Y-linked trait, 120 Yeast artificial chromosome (YAC), 375t Yeast genome, 451 Yellow fever, 286 Yemenite Jews, 293, 293f Yolk sac, 59, 60f Yunis, Jorge, 244 Z Zellweger syndrome, 26 ZIFT See Zygote intrafallopian transfer Zinc finger, 193 Zoloft, 163 Zona pellucida, 57, 58f Zygote, 57, 58f Zygote intrafallopian transfer (ZIFT), 433 ... 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