She is a child of the not-too-distant future. At the same time, clues to health in her genome scan suggest the ideal diet to follow and other interventions that might lower the risk of, or actually prevent, illnesses for which she has inherited susceptibilities. To a biologist, gene has a specific definition -- a sequence of DNA that tells a cell how to assemble amino acids into a particular protein.
To others, "gene" has different meanings: To folksinger Arlo Guthrie, gene means aging without signs of the Huntington disease that claimed his father, legendary folksinger Woody Guthrie. Each of the contributors has been asked to write an account of the position that has been reached in the investigations of a specific topic in one of the branches of human genetics.
It is a storehouse of learning and practical knowledge for anyone interested in environmental policy, biosafety issues, biotechnology processes and associated regulatory constraints. Marcelin Tonye Mahop, Review of European Community and International Environmental Law For bioethicists, legal scholars and regulators struggling with what controls to place on biotechnology, this is required reading.
John Avellanet, Journal of Commercial Biotechnology Biotechnology has prompted a revolution in science and society in the truest sense of the word.
For what superficially appears to be a revolution in biotechnology, in effect touches upon the fundamentals of life and the way in which humans relate to it. This book will make a significant contribution to the debate surrounding the effective regulation of biotechnology. The contributing authors assess how regulatory regimes can accommodate the many different and often conflicting issues to which biotechnology is giving rise to including a very tainted public image.
The book s ultimate aim is to explore ways of designing a regulatory regime that takes heed of these different demands whilst, at the same time, answering to the imperatives of effectiveness and efficiency. These goals collectively serve as the cornerstone of Concepts of Genetics. This pedagogic foundation allows the book to be used in courses with many different approaches and lecture formats. Writing a textbook that achieves these goals and having the opportunity to continually improve on each new edition has been a labor of love for all of us.
The creation of each of the twelve editions is a reflection not only of our passion for teaching genetics, but also of the constructive feedback and encouragement provided by adopters, reviewers, and our students over the past four decades.
New to This Edition New to this edition are four chapters. CRISPR, a genome-editing tool, is a straightforward technique that allows specific, highly accurate modification of DNA sequences within genes and is thus a powerful tool in the world of genetic research and gene therapy.
In addition to this chapter, we call your attention to the introduction to Chapter 1 for an introduction to CRISPR and to also note that we have chosen this gene-editing system as the subject matter illustrated on the cover. Special Topics Chapter 6 illustrates the many of advances that have been made in the study of human neurogenetics. Huntington disease, a monogenic human disorder, has been subjected to analysis for over 40 years using every major approach and technique developed to study molecular genetics, and as such, exemplifies the growing body of information that has accrued regarding its causes, symptoms, and future treatment.
Additional new chapters arise from a major reorganization and expansion of our coverage of regulation of gene expression in eukaryotes, where we have split our previous coverage into three parts: transcriptional regulation Chapter 17 , posttranscriptional regulation Chapter 18 , and epigenetic regulation Chapter This cell is highly simplified. In the breast, epithelial lining cells called lactocytes "milk cells" form tubules, into which they secrete the components of milk.
When the baby suckles, contractile cells squeeze the milk through the tubules and out of holes in the nipples. A Golgi apparatus processes many types of proteins. These products are sorted when they exit the Golgi into different types of vesicles, a little like merchandise leaving a warehouse being packaged into different types of containers, depending upon the destination.
Molecular tags target vesicles to specific locations in the cell, or indicate that the contents are to be released to outside the cell. A type of transport of molecules between cells uses vesicles called exosomes that bud from one cell and then travel to, merge with, and empty their contents into other cells. Exosomes are only 30 to nanometers billionths of a meter in diameter.
They may carry proteins, lipids, and RNA, and have been identified in many cell types. Exosomes remove debris, transport immune system molecules, and provide a vast communication network among cells. Intracellular Digestion—Lysosomes and Peroxisomes Just as clutter and garbage accumulate in an apartment, debris builds up in cells.
Lysosomes are membrane-bounded sacs that contain enzymes that dismantle bacterial remnants, worn-out organelles, and other material such as excess cholesterol figure 2.
The enzymes also break down some digested nutrients into forms that the cell can use. Lysosomes fuse with vesicles carrying debris from outside or within the cell, and the lysosomal enzymes then degrade the contents. These enzymes require a highly acidic environment to function.
A loaded lysosome moves toward the plasma membrane and fuses with it, releasing its digested contents to the outside. Lysosomes maintain the highly acidic environment that their enzymes require to function, without harming other cell parts that acids could destroy. Cells differ in their number of lysosomes. Cells called macrophages that move about and engulf bacteria have many lysosomes. Liver cells require many lysosomes to break down cholesterol, toxins, and drugs. All lysosomes contain forty-three types of digestive enzymes, which must be maintained in balance.
In Tay-Sachs disease, for example, an enzyme is deficient that normally breaks down lipids in the cells that surround nerve cells.
As the nervous system becomes buried in lipid, the infant begins to lose skills, such as sight, hearing, and mobility. Even before birth, the lysosomes of affected cells swell. These diseases affect about 10, people worldwide. Peroxisomes are sacs with single outer membranes that are studded with several types of proteins and that house enzymes that perform a variety of functions.
The enzymes catalyze reactions that break down certain lipids and rare biochemicals, synthesize bile acids used in fat digestion, and detoxify compounds that result from exposure to oxygen free radicals. Peroxisomes are large and abundant in liver and kidney cells, which handle toxins.
Early symptoms of ALD include low blood sugar, skin darkening, muscle weakness, visual loss, altered behavior and cognition, and irregular heartbeat. The patient eventually loses control over the limbs and usually dies within a few years.
Lorenzo lived 30 years, which may have been due to the oil, or to the excellent supportive care that he received.
Providing a functional copy of the gene, called gene therapy, can halt progression of the disease. Gene therapy for ALD is being tested on newborns who have the disease. Chapter 20 discusses gene therapy. Cristae Outer membrane Inner membrane Energy Production—Mitochondria Cells require continual energy to power the chemical reactions of life.
Organelles called mitochondria provide energy by breaking the chemical bonds that hold together the nutrient molecules in food. A mitochondrion has an outer membrane similar to those in the ER and Golgi apparatus and an inner membrane that forms folds called cristae figure 2.
These folds hold enzymes that catalyze the biochemical reactions that release energy from nutrient molecules. The freed energy is captured and stored in the bonds that hold together a molecule called adenosine triphosphate ATP. In this way, ATP functions a little like an energy debit card. A cell may have a few hundred to tens of thousands of mitochondria, depending upon activity level.
A typical liver cell has about 1, mitochondria, but a muscle cell, with its very high energy requirements, may have 10, A major symptom of diseases that affect mitochondria is fatigue.
Chapter 5 discusses mitochondrial inheritance and disease, and chapter 16 describes how mitochondrial genes provide insights into early human migrations. Biological Membranes Just as the character of a community is molded by the people who enter and leave it, the special characteristics of different cell types are shaped in part by the substances that enter and 0.
Cristae, which are infoldings of the inner membrane of a mitochondrion, increase the available surface area containing enzymes for energy reactions. The plasma membrane completely surrounds the cell and monitors the movements of molecules in and out.
How the chemicals that comprise the plasma membrane associate with each other determines which substances can enter or leave the cell. Membrane Structure A biological membrane has a distinctive structure. It is a double layer bilayer of molecules called phospholipids. A phospholipid is a fat molecule with attached phosphate groups. A phosphate group PO4 is a phosphorus atom bonded to four oxygen atoms. A phospholipid is depicted as a head with two parallel tails, shown in the inset to figure 2.
The tendency of lipid molecules to self-assemble into sheets makes the formation of biological membranes possible. Because of these forces, phospholipid molecules in water spontaneously form bilayers. Their hydrophilic surfaces are exposed to the watery exterior and interior of the cell. The hydrophobic surfaces face each other on the inside of the bilayer, away from water, and block entry and exit to most substances that dissolve in water.
Some membrane proteins form channels for ions atoms or molecules with electrical charge. For example, figure 1. Another type of channelopathy can cause either extreme pain in response to no apparent stimulus, or lack of pain. A famous case involved a boy who became a performer, walking on hot coals and stabbing himself to entertain crowds in Pakistan.
Researchers are invesHydrophilic tigating these pain syndromes to develop head new painkillers. Hydrophobic Proteins are embedded in the tail phospholipid bilayer of biological membranes. Some proteins traverse the entire structure, while others extend from one or both faces figure 2. The phospholipid bilayer is oily, and some proteins move within it like ships on a sea. The molecule that binds to the receptor, called the ligand, may set into motion a cascade of chemical reactions inside the cell that carries out a particular activity, such as dividing.
In a different process called cellular adhesion, the plasma membrane helps cells attach to certain other cells. These cell-to-cell connections are important in forming tissues. Faulty signal transduction or cellular adhesion can harm health. Cancer cells also have abnormal cellular adhesion, which enables them to invade healthy tissue. The proteins of the cytoskeleton are continually broken down and built up as a cell performs specific activities.
Some cytoskeletal elements function as rails that transport cellular contents; other parts, called motor molecules, power the movement of organelles along these rails as they convert chemical energy into mechanical energy. Mobile proteins are embedded throughout a phospholipid bilayer. The inset left shows a phospholipid molecule. The three major components of the cytoskeleton are microtubules, intermediate filaments, and microfilaments. Using special stains, the cytoskeletons in the cells in the inset appear orange under the microscope.
The abbreviation nm stands for nanometer, which is a billionth of a meter. They are distinguished by protein type, diameter, and how they aggregate into larger structures. Long, hollow microtubules provide many cellular movements. A microtubule is composed of pairs dimers of a protein, called tubulin, assembled into a hollow tube.
Adding or removing tubulin molecules changes the length of the microtubule. Cells contain both formed microtubules and individual tubulin molecules. When the cell requires microtubules to carry out a specific function—cell division, for example—free tubulin dimers self-assemble into more microtubules. Cells perpetually build up and break down microtubules. Microtubules maintain cellular organization and enable transport of substances within the cell.
Abnormal microtubules cause several neurodegenerative diseases. For example, they may prevent neurotransmitters from reaching the synapses between neurons or between neurons and muscle cells. Cilia are of two types: motile cilia that move, and primary cilia that do not move but serve a sensory function.
Motile cilia have one more pair of microtubules than primary microtubules. Coordinated movement of motile cilia generates a wave that moves the cell or propels substances along its surface. Similarly, motile cilia pass inhaled particles up and out of respiratory tubules and move egg cells in the female reproductive tract. Because motile cilia are so widespread, defects in them can cause multiple symptoms. There are several types of Bardet-Biedl syndrome, and the condition affects both motile and primary cilia.
Many types of cells have primary cilia, which do not move and serve as antennae, sensing signals from outside cells and passing them to specific locations inside cells. Primary cilia sense light entering the eyes, urine leaving the kidney tubules, blood flowing from vessels in the heart, and pressure on cartilage. Although these cilia do not move, they stimulate some cells to move, such as those that form organs in an embryo, and cells that help wounds to heal.
Absence of primary cilia can harm health, such as in polycystic kidney disease. Cells may have many motile cilia but usually have only one cilium that does not move. Microfilaments are long, thin rods composed of many molecules of the protein actin. They are solid and narrower than microtubules, enable cells to withstand stretching and compression, and help anchor one cell to another. Microfilaments provide many other functions in the cell through proteins that interact with actin.
When any of these proteins is Mucus Cilia Epithelial cells Figure 2. Motile cilia move secretions such as mucus on the cell surfaces of the respiratory tubes. In contrast, primary cilia do not move, functioning like antennae to sense changes. This figure shows only motile cilia. In her neurons, different types of intermediate filament proteins accumulate, swelling the long nerve extensions axons that send messages to her muscles. Hannah is one of a few dozen people in the world known to have giant axonal neuropathy GAN.
When Hannah was born on March 5, , her parents and sisters were charmed that her hair was kinky while theirs was stick-straight. All seemed well until Hannah was 2 years, 5 months old, and her grandmother noticed her left arch rolling inward. Doctors thought she would outgrow it, but by her third birthday, both arches were involved and her gait had become awkward.
Still physicians were not alarmed. With the idea of muscular dystrophy mentioned to the pediatrician, Hannah finally had genetic testing for the more common inherited childhood neurological conditions, but results were all normal. Lori and Matt were devastated when a genetic counselor told them that there were no treatments and no research on the extremely rare disease. The actin part of the cytoskeleton is abnormal in Alzheimer disease and in some diseases of heart muscle.
Intermediate filaments have diameters intermediate between those of microtubules and microfilaments, and unlike those other components of the cytoskeleton, intermediate filaments are composed of different types of proteins in different cell types.
However, all intermediate filaments consist of paired proteins entwined to form nested coiled rods. Intermediate filaments are scarce in many cell types but are abundant in nerve cells and skin cells. Her beautiful curls are one of the symptoms, but she prefers today to straighten her hair. Courtesy, Lori Sames. Wendy Josephs Hannah received functional gigaxonin genes just after her twelfth birthday.
By that time, she was using a wheelchair and beginning to have trouble speaking and seeing. If all goes well, the gene therapy will halt the progression of the disease. Meanwhile, Hannah is working hard to strengthen her muscles. Gene therapy into the spinal cord may be developed to treat other, more common conditions, and perhaps spinal cord injuries.
Questions for Discussion 1. Why is the experimental gene therapy for GAN important, even though only a few people have this disease? What is unusual about intermediate filaments, compared to microtubules and microfilaments? Did the pediatric neurologist base his diagnosis of Hannah on her genotype or on her phenotype?
Distinguish prokaryotic from eukaryotic cells. List the chemical constituents of cells. Explain the general functions of organelles. Describe the organelles that interact as a cell secretes, degrades debris, and acquires energy. Explain how the structure of the plasma membrane enables its functions. List the components of the cytoskeleton and describe some cytoskeletal functions. In a human body, new cells form as old ones die, at different rates in different tissues.
Growth, development, maintaining health, and healing from disease or injury require an intricate interplay between the rates of mitosis and cytokinesis, which divide the DNA and the rest of the cell, respectively, and apoptosis, a form of cell death.
An adult human body consists of about 30 trillion cells, and billions are replaced daily. Cells must die as part of normal development, molding organs much as a sculptor carefully removes clay to shape the desired object. Interphase is divided into two gap G1 and G2 phases and one synthesis S phase. In addition, a cell can exit the cell cycle at G1 to enter a quiet phase called G0. A cell in G0 is alive and maintains its specialized characteristics but does not replicate its DNA or divide.
From G0, a cell may also proceed to mitosis and divide, or die. A series of events called the cell cycle describes the sequence of activities as a cell prepares for and undergoes division. Cell cycle rate varies in different tissues at different times. A cell in the deepest skin layer may divide as long as a person lives, and even divide a few times after a person dies! Frequent mitosis enables the embryo and fetus to grow rapidly.
By birth, the mitotic rate slows dramatically. Later, mitosis maintains the numbers and positions of specialized cells in tissues and organs. The cell cycle is continual, but we describe it with stages. The two major stages are interphase not dividing and mitosis dividing figure 2.
In mitosis, a cell duplicates its chromosomes, then in cytokinesis it apportions one set of chromosomes, along with organelles, into each of two resulting cells, called daughter cells.
Mitosis maintains the set of 23 chromosome pairs characteristic of a human somatic cell. Another form of cell division, meiosis, produces sperm or eggs, which have half the amount of genetic material that somatic cells do or 23 single chromosomes, comprising one copy of the genome. Chapter 3 discusses meiosis in the context of development. Inter pha se 2. In syndactyly, apoptosis fails to carve digits, and webbing persists, as it does in these hands.
The cell cycle is divided into interphase, when cellular components are replicated, and mitosis, when the cell distributes its contents into two daughter cells. Interphase is divided into G1 and G2, when the cell duplicates specific molecules and structures, and S phase, when it replicates DNA. Mitosis is divided into four stages plus cytokinesis, when the cells separate.
During G1, which follows mitosis, the cell resumes synthesis of proteins, lipids, and carbohydrates. These molecules will contribute to building the extra plasma membrane required to surround the two new cells that form from the original one. G1 is the period of the cell cycle that varies the most in duration among different cell types. Slowly dividing cells, such as those in the liver, may exit at G1 and enter G0, where they remain for years.
In contrast, the rapidly dividing cells in bone marrow speed through G1 in 16 to 24 hours. Cells of the early embryo may skip G1 entirely. During S phase, the cell replicates its entire genome. This happens simultaneously from several starting points, to get the enormous job done.
After DNA replication, each chromosome consists of two copies of the genome joined at an area called the centromere. In most human cells, S phase takes 8 to 10 hours.
Many proteins are also synthesized during this phase, including those that form the mitotic spindle, which will pull the chromosomes apart.
Microtubules form structures called centrioles near the nucleus. Centriole microtubules join with other proteins and are oriented at right angles to each other, forming paired, oblong structures called centrosomes that organize other microtubules into the spindle. G2 occurs after the DNA has been replicated but before mitosis begins. More proteins are synthesized during this phase. Membranes are assembled from molecules made during G1 and are stored as small, empty vesicles beneath the plasma membrane.
These vesicles will merge with the plasma membrane to make enough of a boundary to enclose the two daughter cells. Chromosomes are replicated during S phase, before mitosis begins.
Two genetically identical chromatids of a replicated chromosome join at the centromere a. The photomicrograph b shows a replicated human chromosome. The long strands of chromosomal material in replicated chromosomes are called chromatids, and if attached at a centromere, they are called sister chromatids. The space between sister chromatids is called a furrow figure 2.
This allows its sister chromatids to separate into two individual chromosomes. So a chromosome can be in an unreplicated form, in a replicated form consisting of two sister chromatids, or unwound and not visible when stained. Although the centromere of a replicated chromosome appears as a constriction, its DNA is replicated.
During prophase, the first stage of mitosis, DNA coils tightly. Replicated chromosomes separate and are distributed into two cells from one. In a separate process called cytokinesis, the cytoplasm and other cellular structures distribute and pinch off into two daughter cells. Not all chromosome pairs are depicted. Prophase Condensed chromosomes take up stain.
The spindle assembles, centrioles appear, and the nuclear envelope breaks down. Microtubules assemble from tubulin building blocks in the cytoplasm, forming the spindles. Toward the end of prophase, the nuclear membrane breaks down.
The nucleolus is no longer visible. Metaphase follows prophase. Chromosomes attach to the spindle at their centromeres and align along the center of the cell, which is called the equator. Metaphase chromosomes are under great tension, but they appear motionless because they are pulled with equal force on both sides, like a tug-of-war rope pulled taut. Next, during anaphase, the plasma membrane indents at the center, where the metaphase chromosomes line up. A band of microfilaments forms on the inside face of the plasma membrane, constricting the cell down the middle.
Then the centromeres part, which relieves the tension and releases one chromatid from each pair to move to opposite ends of the cell—like a tug-of-war rope breaking in the middle and the participants falling into two groups. Microtubule movements stretch the dividing cell. Apply Learning Outcome: Which of the following statements is true? Somatic cells are diploid, meaning that they have two copies of the human genome. Somatic cells are haploid, meaning that they have one copy of the human genome.
Sperm and egg cells are diploid, meaning that they have two copies of the human genome. Stem cells are haploid, meaning that they have one copy of the human genome. Which of the following types of components aggregate and interact to form the epithelial, connective, muscle, and nerve tissues in the human body? Prokaryotic cell. Remember Learning Outcome: Prokarya; organelles B. Archaea; ancient organelles C. Eukarya; organelles D.
The major macromolecules that make up cells are A. Organelles protect a cell by A.
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