Allele - Because in all animals and plants chromosomes come in pairs, there are always two versions of each gene. Each of these alternative forms of a gene is called an allele. A single allele for each location on the chromosome is inherited separately from each parent. Alleles can differ or be identical. They produce variations in inherited traits such as blood type and eye color. The impact of an allele on such traits depends on whether it is dominant, recessive, or co-dominant.

Amniocentesis - Amniocentesis is a way to test particular genetic predispositions of a fetus. A hollow tube is inserted through the abdomen into the uterus to withdraw a small amount of fluid from the amniotic sac that surrounds a fetus. Usually conducted towards the end of the first trimester of pregnancy, the test is used to detect chromosomal and genetic disorders like Down's syndrome and Tay-Sachs disease. It also reveals the gender of the fetus. New genetic diseases are continually being added to the list of disorders for which amniocentesis can test.

Women like the one played by Meredith Vieira in Making Better Babies are often advised to undergo amniocentesis, because in mothers over 35 the incidence of Down's syndrome and other genetic problems increases. Women with a family history of certain genetic diseases are also encouraged to be tested.

Bioethics - New medical technologies carry risks along with benefits, and generate new ethical questions. Bioethics is the systematic study of the ethical and moral implications of new biological discoveries and biomedical advances, particularly in genetic engineering and drug research. Bioethicists try to provide ethical guidelines for doctors, patients, and families faced with complex quality-of-life decisions. Their skills apply to a wide range of medical and moral issues like the definition of death, the nature of informed consent, the appropriate use of fetal tissue, genetic engineering, and guidelines for research on human subjects.

Some of the principles central to bioethical thinking are:

• respect for the person (what is best for the individual?);
• fairness (equal access under the law to information and treatment); and
• beneficence (that we do good rather than bad).

Cancer - The general term "cancer" refers to a group of nearly 100 diseases in which abnormal cells divide and grow unchecked. Cancer can arise in many different organs. If the disease spreads uncontrollably, it can be fatal. Cancer is expected to overtake heart disease as the leading cause of death in the United States early in the 21st century. However, nearly half of all cancer patients can expect to be alive and free of symptoms five years after diagnosis. Research into the disease at the molecular level and into the role played by genetics may yield new cancer treatments—even cures.

Cell - Cells are watery, chemical-filled, self-contained, membrane-bound compartments. Bacterial cells contain one complete copy of all the genes needed to code for that type of bacteria, whereas all plants and animals contain two complete copies of the genes.

Chromosome - These are structures in the nucleus of a cell that contain the genes. The human genome is distributed among the 46 chromosomes that a normal cell contains. Chromosomes come in pairs. These 23 sets of chromosomes are made up of 22 pairs of autosomes and one pair of sex chromosomes. (Sex chromosomes specify an organism's gender; all the rest are autosomes.) During reproduction, when sperm meets egg, chromosomes replicate. This means that our full genome is contained along our chromosomes in each of our body's several trillion cells.

Most genetic defects are not structural chromosomal problems, but rather defects that occur when base pairs in the DNA within the chromosome are missing or transposed. However, a small percentage of genetic defects consist of chromosomal inversions, like the one for which the fetus in the Making Better Babies program tests positive. Such structural deformities in the chromosome itself occur when a piece of the chromosome breaks off and flips over, causing mutations at the two points where it reattaches. While chromosomal abnormalities are easier to detect because of their larger scale, the health consequences are not necessarily greater than those of other genetic defects.

Clone - A clone is a group of identical genes, cells, or organisms derived from a single ancestor. Identical twins are clones.

Cloning - This is the process of creating genetically identical copies of an organism. Cloning typically involves a technique called nuclear transfer, in which the nucleus of the recipient egg is sucked out with a needle and replaced by the nucleus of a cell from the future clone. Then the egg is activated via an electrical or chemical signal that mimics fertilization. Cell division begins, generating an embryo whose DNA will be 95 percent identical to the donor's; the other five percent is mitochondrial DNA, which comes from the host, or maternal, cell. Within a few days, the embryo is a mass of cells large enough to implant in the uterus of the surrogate mother.

The first mammal to be cloned was Dolly the sheep, in 1997. The achievement was especially notable because she was created using a non-reproductive cell—in this case, a cell from a mammary gland. Since then, beef and dairy producers have turned to cloning prized animals, conducting the first auction of a cloned dairy cow in 2000.

In popular imagination, the next step tends to be a future full of identical humans and duplicated doggies. But in practice, the failure rate is high. Dolly was preceded by 277 failed attempts. It typically takes 100 tries to clone a live calf, and even in the most efficient animal cloning labs, fewer than five percent of nuclear transfer attempts result in live births. In addition, the long-term health effects of cloning are still unclear.

While cloning humans is technically possible, hundreds of cloned embryos might have to be implanted in order to create a single child with current technology. Ethically, this is a deeply troubling scenario. Nor do we know whether that child would suffer from cloning-related genetic abnormalities. It is important to remember that the clone or child would not be a duplicate of the cell donor. Identical twins, even though they share the same genes and are usually raised in the same environment, exhibit very different abilities, disabilities, and personalities. While opinion polls show that most people oppose the idea of human cloning, many experts think it's only a matter of time until a human clone is produced.

More interesting to many scientists is the promise of "therapeutic cloning." This involves using embryonic stem cells to help people who are severely ill with conditions like Alzheimer's or organ failure. A cell nucleus from the patient is inserted into an emptied donor egg, which then develops into an embryo whose genome is identical to the patient's: a clone. Stem cells, which have the potential to develop into any kind of tissue, could then be "harvested" from the microscopic embryo and transplanted back into the sick person without being rejected. Here too, however, the prospect of generating human embryos for "utilitarian" purposes raises complex ethical questions.

Complex trait - Some traits, like attached earlobes, the ability to curl the tongue, and diseases such as sickle cell anemia and Huntington's disease, are simple. These are controlled by a single gene, which makes them easily identifiable, and they involve no known environmental interaction. Most traits, however, are complex. These include the majority of syndromes that affect our health, like cancers and heart disease; physical attributes like height and weight; and perhaps some social characteristics. Both genes and environment contribute to the expression of complex traits, which makes them extremely difficult to study.

We're beginning to decipher the genetic basis for a number of complex diseases. But although we know which genes contribute to the production of breast cancer, for example, we don't understand what turns them on and why they're active at some times and not others.

DNA - (deoxyribonucleic acid) - DNA is the molecule that encodes genetic information. DNA takes the form of two long strands that twist into a spiral—the famous double helix. The helix is held together by weak bonds between its four chemical components which are paired—adenine (A) in one strand to thymine (T) in the other, and cytosine (C) to guanine (G). Each bond makes up a base pair. When the double helix "unzips," each side becomes a template for the replication of that DNA molecule, a process that occurs an infinite number of times in each human. DNA is found in every human cell, and the human genome contains about 3.1 billion base pairs.

Segments of DNA form instructions that guide cell function. These segments are called genes.

Eugenics - Eugenics, according to Francis Galton, is the science of "improving human stock by giving more suitable races or strains of blood a better chance of prevailing speedily over the less suitable." It was popular around the world during the first half of the 20th century. Negative eugenicists advocated the so-called improvement by preventing, by force or by coercion, unsuitable individuals from reproducing. Positive eugenicists sought eugenic improvements only through breeding what they deemed superior human stock. During the 1920s and '30s approximately 30,000 Americans were sterilized under state eugenic laws, and eugenics was a central part of the practice and dogma of the Third Riech's Nazi doctrine. Changes in biological science coupled with aversion to Nazism led to the downfall of popular eugenics. However it is worth recalling its popularity when considering the potential abuses of genetic engineering and genetic enhancement that we may face in the future.

Founder effect - This is an evolutionary process that occurs when new populations are started by a small number of individuals that have broken off from a larger group. This new population carries lower overall genetic variability of their parent population. The resulting founder effect sometimes concentrates a particular gene in the newly isolated population. This can have harmful effects, because recessive traits are more likely to express themselves in the absence of genetic diversity.

The fact that founder populations have less heterogeneity in their DNA makes them attractive subjects for genetic studies. As Francis Collins explains in the Genes On Trial program, "from a scientific perspective, it means we have a better chance of finding the answer than if we look at a very outbred group with lots of different genetic contributions coming from lots of places."

Gene - The gene refers to a section of DNA, and is the fundamental unit of heredity. Every living thing, from buffalo to bacteria, has genes, which transmit information from one generation to the next. Each of the human body's approximately 30,000 genes contains the code for building a specific product, typically the proteins that make our bodies function.

"A gene for . . ." - This is the kind of language that gets us in trouble. It's natural for people to want simple answers. Even scientists say things like, "Oh, we've located a gene for alcoholism." But speaking about it in this way is essentially incorrect. There is no gene for alcoholism, nor, in most cases, for cancer. A genetic susceptibility to alcoholism doesn't mean you have a genetic predisposition to drink, but that you have a gene that predisposes you to become addicted to a particular substance—in this case, alcohol. The gene is for the way an individual processes alcohol, not for the behavior of alcoholism. Furthermore, not all alcoholics have this gene; many people drink because of the role it plays in their social or psychological well being. When it comes to heroin, between a third and a fifth of users become addicted within their first couple of tries because of the way their body metabolizes the drug. These people possess a genetic marker for heroin addiction. Others without the marker may well become addicted, but their physiological response is different.

In the case of some conditions, like Huntington's disease and sickle cell anemia, scientists know that the cause is genetic. Because such conditions are single-gene linked, they are more detectable by our rudimentary technologies, which is why we know relatively more about them. But while there are indeed "genes for" this small subcategory of diseases, they represent a tiny minority of traits in which genes play a role. There are not specific "genes for" traits such as obesity or intelligence, because these are the result of layers of interactions between many genes and ever-changing environmental factors.

Gene therapy - Developed in the 1970s, this technology delivers working genes into cells in which a gene is either missing or malfunctioning. There are two types of gene therapy. Somatic therapy targets non-reproductive cells; the engineered cells die with the individual. Germ line therapy is performed on reproductive cells (sperm, egg, gamete, or zygote), which means that the altered gene will be present in every cell of any offspring.

Although gene therapy has yet to deliver on its promise, the possibility of treating inherited diseases at their very roots—by repairing the associated "flaw" in the DNA code—is extremely exciting. Gene therapy is currently in clinical trials to treat AIDS, cancer, heart disease, muscular dystrophy, cystic fibrosis, and metabolic and immune disorders.

The major challenge has been finding a good way to deliver corrective DNA to the appropriate cells. Because a virus can replace a cell's genetic material with its own, scientists have been substituting corrective DNA for the virus's own DNA and dispatching the altered virus into the patient's body. But this delivery mechanism is inexact. A gene replacement or gene surgery technique for human cells has yet to be developed, but scientists hope to accomplish this feat in the not-too-distant future.

Recently, gene therapy celebrated its first major success. At a French hospital, four babies with severe combined immunodeficiency disease (known as the "bubble boy" disease) were provided with a normal copy of the defective gene that impairs development of the immune system. The boys—the disease is inherited on the X chromosome—are living at home and developing normally.

Genes + exposure + time = outcome* - There's something almost comforting about the notion that our fate is written in our genes. But this is seldom the case: much of the difference among individuals has nothing to do with genes. Even identical twins, who share the same complete genome or genotypes, can have varying expressions of these genes—known as their phenotypes. Our differences are rooted in our unique experiences: what we eat; where we live; where we spend our summer vacations. We are the products not of a struggle between nature versus nurture but of interactions between the two: nature and nurture.

By the same token, we are, after all, biological beings, and can never be free of our genetic inheritance. As molecular biologists find new relationships between genes and human characteristics ranging from aging resistance to certain types of diseases, the nature-nurture debate is sure to persist.

Scientists think that people may have genes that predispose them to be susceptible to any number of things in the environment. This accounts for the fact that some develop lung cancer after exposure to secondhand smoke alone, while some heavy smokers never develop lung disease. As the tests for such susceptibilities grow in number and sophistication, sooner or later, everyone will fail a genetic test. That's why understanding the complex reaction between gene and environment is so important.

Because we have considerable control over our environment, we can help shape many outcomes. We know, for example, that a low-fat, high-fiber diet reduces the risk of colon cancer. Nutrition can also make us taller, and early childhood education help us make the most of cognitive abilities.

* The title of this section comes from the article "Environmental Health and Genomics: Visions and Implications" by Samuel Wilson and Ken Oden published in Nature Reviews Genetics 1, 149 - 153 (01 Nov 2000).

Genetic counselor - Genetic counselors are specially trained health professionals who provide information and support to families who may be at risk for a range of genetic disorders or birth defects. Counseling is typically short-term and involves a discussion of reproductive choices, including risks and options and the potential consequences of testing. The genetic counselor's job is to explain what kind of information you can expect from such tests; to make sure you have enough information to formulate a truly informed consent; to help you and your family interpret and adjust to the results; and to arrange whatever prevention and screening measures are appropriate. People enter the field from a variety of disciplines, including biology, genetics, nursing, psychology, public health, and social work.

Genetic discrimination - This takes place when individuals are in some way persecuted or singled out because of their genotype (the entire genetic makeup) or phenotype (the observable characteristics displayed by a cell or organism, such as eye color or a genetic disease). Many different groups are interested in regulating the use that insurers and other parties may make of genetic information. Some form of legislation against genetic discrimination is on the books in approximately forty states, although no comprehensive federal legislation yet exists. Such laws would prohibit discrimination against individuals and their family members based on genetic information or the desire to undergo genetic testing.

Genetic enhancement - In 1972 geneticists figured out how to insert DNA from one organism into another, making it capable of generating new substances or performing new functions. Since then, genetic engineering techniques have been applied to many organisms, creating vitamin-enhanced rice, bacteria that gobble up oil slicks, and biological therapies like insulin. They have given rise to the promising field of gene therapy, in which working genes are delivered into cells to treat disease at its very roots.

But from the very beginning these technologies have fueled dreams of manipulating DNA not just to improve human health, but to create stronger, faster, longer-lived humans. This is genetic enhancement, defined by bioethicist David Rothman as "efforts to make individuals better than well, optimizing their capabilities by taking them from standard levels of performance to peak performance." Possible future enhancements include a decreased need for sleep, better memory, reduced susceptibilities to many common diseases, and features like eye and hair color.

"Designer babies" now belong to the realm of science fiction, but parents may some day be able to modify their embryos so that their children possess specified features. Modifications could have unanticipated negative effects, and ethical concerns abound. If diseases can be cured by altering an individual's genetic makeup, why not "fix" conditions like myopia, short stature, and left-handedness? Would prejudice against people who are obese, short, or mentally disabled increase? Would inequality grow between those who could and could not afford genetic enhancements? Or could access be regulated so that everyone might benefit from these new technologies? No one knows the answers. But few motivators are more powerful than the desire to give your child every possible advantage.

Genetic marker - Also known as a molecular marker, this is a segment of DNA with an identifiable physical location on a chromosome that shows genetic variability between individuals. (It can be part of a gene, or a section of DNA with no known function.) Because DNA is inherited, genetic markers can be used to track patterns of inheritance. This makes genetic markers one of the basic tools of the geneticist. Markers help them to narrow down the possible location of new genes, and to discover the associations between genetic mutations and disease. The presence or absence of genetic markers associated with certain diseases can be used to determine whether someone is at increased risk for developing that disease.

Genetic risk - In many ways, genetics is the study of probability. Genetic tests are often referred to as predictive genetic tests because that's what they do: predict. If you do possess a genetic mutation, the chance that you will contract the disease still depends on a number of factors. (See Genes + exposure + time = outcome.)

Genetic risk also depends on the condition being tested. Some genes express themselves absolutely, some don't, and many fall in between; it's a gradient. If you test positive for the Huntington's disease gene, you will get the disease. If, like Artie, on Who Gets to Know?, you carry the HNPCC abnormality, you will almost certainly develop colon cancer at some point in your life (although many cancers, colon in particular, can be detected, treated, or prevented). Women who carry the BRCA-1 breast cancer susceptibility gene have an 80 percent chance of developing breast cancer by the age of 65; their risk is high but not absolute. Conversely, even family members without the mutation are not home free. Like anyone else, they could develop a genetic mutation during their lifetime that leads to cancer.

Genetic testing - To conduct a genetic test, a laboratory technician examines a blood or tissue sample for specific biochemical, chromosomal, or DNA-based markers that indicate susceptibility to certain diseases. If a genetic test reveals such a susceptibility, the disease may or may not develop. The test can also confirm a diagnosis of a genetic disease. Populations can also be tested in order to identify those at high risk for having or transmitting a specific genetic disorder.

In the United States, newborns are routinely screened for conditions like PKU (phenylketonuria), a metabolic disorder that causes mental retardation if left untreated. Prospective parents are commonly screened to find out if they carry genetic markers for inherited disorders such as cystic fibrosis, sickle cell anemia, or Tay-Sachs disease. Many undergo prenatal testing to see if the fetus is at risk for conditions such as Down's syndrome.

Much attention is now focused on predictive gene testing: tests that identify those at risk of getting a disease, before they experience any symptoms. However, therapies for many such conditions are inadequate or nonexistent, and the knowledge itself can be a great burden to individuals and families.

The number of available genetic tests grows almost daily, but the implications of this information are far from established. We now know that our genetic makeup contributes, along with a strong environmental component, to such common conditions as heart disease and diabetes. But we also know that individual outcomes are far less predictable than a single test result implies. At this point, tests evaluate only the more common mutations, so even a negative test result does not completely rule out the possibility of developing the disease. The gene at work may not be the test gene; for example, only about half of families with hereditary breast cancer test positive for the BRCA-1 gene mutation. Some people with a given genetic marker fall ill while others stay healthy, for reasons we don't understand. (See genetic risk.)

Genetics - Genetics is the branch of biology that deals with heredity: how particular qualities or traits are transmitted from parents to offspring.

Genome - This relatively new term refers to the complete collection of genetic material that is passed down from cell to cell and generation to generation in a given organism. The genome contains the complete set of instructions needed for the development and maintenance of that organism. Except for identical twins, everyone has a unique genome. Yet the differences between one genome and another are, on average, 0.1 percent, which is why we talk about the human genome.

Genomics - Genomics is the study of how all the DNA of a cell, including the full set of genes, interacts to shape physiological traits and evolution.

Human Genome Project - Formally launched in October 1990, the Human Genome Project (HGP) has been called the most ambitious scientific undertaking ever attempted. The goal of this international research project is to discover all the approximately 30,000 human genes (the human genome), make them accessible for further study, and determine the complete sequence of all 3 billion DNA base pairs within it. The first draft of the human genome was completed in 2000, far faster than initially projected, and the consortium is analyzing this information. It's also sequencing the genome of many other model organisms—yeast, over 100 bacterial species, a fly, a worm, a mouse, among others—to help develop the technology and interpret human gene function.

A health-motivated project, the HGP will provide better understanding of human susceptibility to diseases and lead to new ways to treat, prevent, and cure them. It will also establish the evolutionary relationship between humans and other organisms.

Huntington's disease - This is a degenerative brain disorder that typically affects people between ages 30 and 50. Early symptoms include slight, uncontrollable muscular movements, clumsiness, memory lapses, and mood swings. Motor, cognitive, and behavioral problems grow more severe as the disease progresses. It is generally fatal within 20 years.

In 1993, geneticists learned that Huntington's disease (HD) is caused by a faulty gene near the tip of chromosome 4. Each person whose parent has Huntington's disease is born with a 50-50 chance of inheriting the faulty gene. Anyone who inherits the faulty gene will, at some stage, develop the disease. Working primarily with mice, scientists have been able to establish animal models that mimic the effects of HD. They're using these animal models to screen for drugs that may delay or stop the progression of the disease in humans.

Informed consent - This is the process in which a person is given all the relevant information about a health care decision and voluntarily agrees to it. The concept is based on the principle that a physician has a duty to disclose information that allows the patient to be an informed participant in his or her own treatment. An informed consent discussion generally covers the nature of the decision or procedure in question; the risks and benefits of participation vs. non-participation; and any reasonable alternatives. Potential participants should also be informed of the goals of the study, disclosure policies, and financial and time commitments involved. The physician is also generally obligated to provide a recommendation, to share her reasoning, and to make sure the patient understands the full range of possible choices and outcomes.

There is an ongoing debate over how informed consent applies to special populations like children and the mentally ill. It's also not clear how genomic technologies will change the informed consent process because of the way in which genetic information is not necessarily specific to the individual.

In vitro fertilization - In vitro fertilization (IVF) is a technique that enables a human embryo to be conceived outside the mother's body. Normally, fertilization—when egg and sperm join together—occurs within the woman's fallopian tube. In IVF, eggs and sperm are collected and placed in a laboratory dish (the "vitro," or glass, that gives the procedure its name). Several days later, the fertilized and dividing eggs can be transferred to the woman's uterus to continue growing. Louise Brown, the world's first "test-tube" baby, who was born in 1978, now has plenty of healthy company, and IVF has provided a means for many otherwise infertile women to give birth.

Although the IVF procedure itself need not involve genetic manipulation of the embryo, it introduced an unprecedented level of human intervention in the reproductive process. Advances in reproductive technology now make it possible for life to be not just created but altered during the in vitro process, which remains the only way of obtaining an embryo in the very early stages of development. (See pre-implantation diagnosis, repro-genetic technologies.)

Mutation - A mutation has come to be defined as a change in the DNA sequence of an organism. It may have no measurable effect on the organism, or it could be harmful or beneficial. Most mutations are random errors that occur during cellular replication. They and their effects are generally unpredictable. Some mutations in cells die with the organism, while those that affect reproductive cells can be passed between generations.

Nucleus - The nucleus is the central structure inside a cell that contains the chromosomes and governs cell growth, metabolism, and reproduction.

Pre-implantation diagnosis - This is a procedure for screening embryos for a number of inherited disorders, including cystic fibrosis, Tay-Sachs disease, hemophilia, Fragile X syndrome, and rarer conditions such as Barth syndrome and Rett syndrome. Pre-implantation diagnosis is usually requested by prospective parents whose offspring are at a high risk (25-50 percent) for a specific genetic condition because one or both parents are carriers or affected by the disease. It offers an alternative to being tested once pregnancy has occurred, in which case parents face the dilemma of whether to terminate the pregnancy if the fetus indeed carries the genetic disorder. With pre-implantation diagnosis, parents receive the information before the embryo is implanted in the woman.

As in a standard in vitro fertilization (IVF) procedure, eggs and sperm are combined in a laboratory dish and observed until they have reached about the 8-cell level. At this point one or two cells are removed—which does not impair development—and analyzed. Typically, three of the embryos that are free of abnormalities are implanted in the woman's womb, and the others are destroyed. Almost all genetically inherited conditions that are diagnosed in the prenatal period can also be detected in the pre-implantation period. Although it presents a welcome alternative to fetal diagnosis and abortion, the notion of submitting embryos to "quality control" raises ethical issues. These issues are bound to become more problematic as the list of traits that can be screened for grows longer and more nuanced.

Turner syndrome - In the Making Better Babies program, panelists Meredith Vieira and Lee Silver face the hypothetical prospect of giving birth to a child with Turner syndrome. This sex-linked condition occurs when one of the two X chromosomes normally found in females is missing or incomplete. It's one of the most common chromosomal abnormalities, occurring in about 1 out of 2,500 live female births. People with Turner syndrome are almost always short and infertile, and may also suffer from cardiovascular problems, kidney and thyroid problems, skeletal disorders, and hearing and ear disturbances.