1. Explain the five elements of Mendel’s theory. What modern Laws of Heredity were produced from Mendel’s theory?

To explain his results, Mendel proposed a theory that has become the foundation of the science of genetics. His theory has five elements.

1 Parents do not transmit traits directly to their offspring. Rather, they pass on units of information that operate in the offspring to produce the trait. Mendel called these units of information "factors". In modern terminology., Mendel’s factors are called genes. A gene is a segment of a DNA molecule that transmits hereditary information.

2. For each trait, and individual has two factors: one from its mother and one from its father. The two factors may or may not have the same information. If the factors have the same information. If the factors the same information (for example, if both factors have information for purple flowers), the individual is said to be homozygous. If the factors are different (for example, one factor has information for purple flowers and the other has information for white flowers), the individual is said to be heterozygous. Each copy of a factor, or gene, is called an allele.

3. In modern terms, the physical appearance, or phenotype, of an individual is determined by the alleles that code for traits. The set of alleles that an individual has is called its genotype.

4. An individual receives one allele from one parent and the other allele from the other parent. Each allele can be passed on when the individual matures and reproduces.

5. The presence of an allele does not guarantee that a trait will be expressed in the individual that carries it. In heterozygous individuals, only the dominant allele is expressed; the recessive allele is present but unexpressed.

Mendel’s theory brilliantly predicts the results of his crosses and also accounts for the ratios he observed. Similar patterns of heredity have since been observed in countless other organisms. Because of its overwhelming importance, Mendel’s theory is often referred to as the law of segregation. In modern terms, the law of segregation states that the members of each pair of alleles separate when gametes are formed.

Mendel went on to study how different pairs of genes are inherited, such as the genes for flower color and plant height. He found that for the pairs of traits he studied, the inheritance of one trait did not influence the inheritance of any other trait. This observation eventually became known as the law of independent assortment. The law of independent assortment states that pairs of alleles separate independently of one another during gamete formation. We now know that this principle applies only to genes located on different chromosomes or far apart on the same chromosomes.

Mendel’s paper describing his results was published in 1866. Unfortunately, it failed to arouse much interest and was forgotten. In 1900, sixteen years after Mendel’s death, several scientists independently rediscovered the pioneering paper. They had been searching the literature in preparation for publishing their own findings, which were similar to those Mendel had quietly presented more than three decades earlier.

2. Describe the experiments performed by Mendel using garden peas. What would have happened if Mendel would have used snap dragons?

For his experiments, Mendel chose to study the garden pea. The garden pea is a good subject for genetic study for several reasons.

1. Many varieties of P. sativum exist. Mendel initially examined 32 varieties. From these he selected seven pairs of varieties that differed in easily distinguishable forms of various traits, such as flower color, seed color, and seed shape.

2. Mendel knew from earlier experiments that he could expect one of the two forms of each trait to disappear in one generation and then reappear in the next. This gave him something to count.

3. P. sativum is a small, easy-to-grow plan that matures quickly and produces a large number of offspring. Mendel would be able to conduct many experiments and obtain results quickly.

4. The male and female reproductive parts of P. sativum are enclosed within the same flower. When left undisturbed, the flower does not open fully; it simply fertilizes itself through a process called self-pollination. As a result, one individual plant can produce offspring. To cross two pea plants, Mendel first had to remove the anthers (the pollen-producing organs) from a flower of one plant. He could then dust the pistil (the egg-producing organ) with pollen from a flower of a different pea plant. Transferring the pollen from the flower of one plant to the flower of a different plant is called cross-pollination. Scientists use the term cross to refer to the breeding between two flowers from separate plants.

Mendel carried out his experiments with garden peas in three steps.

1. Step 1: Mendel began his experiments by allowing each variety of garden pea to self-pollinate for several generations. This method ensured that each variety was true-breeding for a particular trait, which means that all the offspring would display only one form of a particular trait. For example, a true-breeding, purple-flowering plant produced only plants with purple flowers in subsequent generations. Mendel called these plants the parental generation, or P generation.

2. Step 2: Mendel then cross-pollinated two varieties from the P generation that exhibited contrasting traits such as purple flowers and white flowers. He called the offspring of these plants the first filial generation, or F₁ generation.

3. Step 3: Finally, Mendel allowed the F₁ generation to self-pollinate. He called the offspring of these plants the second filial generation, or F₂ generation. These were the plants that he counted.

For each cross, Mendel obtained F₁ generation plants that had only one form of the crossed traits. The contrasting trait had disappeared. Mendel described the remaining, or expressed trait, as dominant. The trait that was not expressed in the F₁ generation was described as recessive. The table below identifies the dominant and recessive forms of the seven traits that Mendel studied.

When the F₁ generation was allowed to self-pollinate, the recessive trait reappeared in some of the plants in the F₂ generation. At this point Mendel counted each type of plant in the F₂ generation. For example, he counted 705 plants with purple flowers and 224 plants with white flowers. From these data, Mendel calculated a ratio of approximately 3 purple-flowering plants to every 1 white-flowering plant (3:1). For each cross, Mendel obtained the same 3:1 ratio of plants expressing the dominant trait to plants expressing the recessive trait. The Table above lists the numbers of F₂ individuals and the ratios Mendel obtained for each cross.

Mendel’s next question was, will the 3:1 ratios continue in subsequent generations? He found that plants showing the recessive traits were true-breeding, whereas two-thirds were not. For these plants, Mendel observed a 3:1 ratio of dominant to recessive traits. These results suggested that the 3:1 ratio in the F₂ generation was really a disguised 1:2:1 ratio: 1 true-breeding dominant plant to 2 not-true-breeding dominant plants to 1 true-breeding recessive plant.

Dominant and recessive characteristics are not always as clear-cut as in the seven traits studied by Mendel in the pea plant. Some characteristics appear to blend. For instance, as Bateson and Punnett showed in 1906, a cross between a homozygous red-flowering snapdragon (RR) and a homozygous white-flowering snapdragon (rr) produces heterozygous that are pink, a phenotype intermediate between those of the homozygous. Mendel’s observations would have no value if he would have used snap dragons since the two traits are intermediate. This phenomenon is known as incomplete dominance. It is a result of the combined effects of gene products. When the heterozygous pink snapdragons are allowed to self-pollinate, red and white characteristics sort themselves out once again, showing the alleles themselves, as Mendel had asserted, remain discrete and unaltered. A cross between a red and white snapdragon is very much like the cross between a purple and white flowering pea plant. There is a significant difference because in this case neither allele is dominant. The flower of the heterozygote is a blend of the two colors. Mendel, could not recognize between the two traits for his results if he would have used snapdragons.

3. Explain the Laws of Probability.

Probability is a branch of mathematics that deals with the likelihood of observing one of several possible outcomes that can occur in an event. In probability, an event is a single happening—sometimes called a trial—and an outcome is one of the possible results. For example, one toss of a coin is an event, whereas a head or a tail is an outcome. The determination of probabilities is important in many practical activities. For example, manufacturers need to know the likelihood that a randomly selected product is flawed; personnel managers need to know the likelihood that a person hired for a job will succeed; insurance companies need to know the likelihood that a client will have an accident in a given year.

In the 17^th century the Swiss mathematician Jacques Bernoulli showed how to make predictions involving combinations of events with two possible outcomes, as in the tossing of three pennies, with each landing heads or tails. In that century two French mathematicians, Blaise Pascal and Pierre de Fermat, also discussed probability theory as it related to games of chance. In the 18^th century a French mathematician, Abraham De Moivre, studied such games and developed the distribution of possible outcomes known as the bell-shaped curve or normal distribution. This curve was also independently developed in that century by the French mathematician Pierre Simon de Laplace, who applied it to astronomical observations. Adolphe Quetelet, a 19^th- century Belgian scientist, fostered the idea that the curve could be applied in many fields, and in this way introduced the use of probabilistic models into most sciences. In 1929, Russian mathematician A. N. Kolmogorov gave the science of probability a rigorous foundation when he published a set of axioms that could be used to develop theories of probability.

In the most straightforward case, probability theory deals with a set of outcomes that are equally likely to occur. For example, if a card is drawn from a deck (a random event), it is equally likely to be a heart, a spade, a diamond, or a club. In this case probability is found by dividing the number of outcomes of a given kind (say hearts) by the total number of possible outcomes. An outcome is called a sample; all possible outcomes are called the sample space.

Probability can also be viewed as the relative frequency of an outcome in a long sequence of events. This view is often called the empirical approach, because probabilities are based on data accumulated from a number of random samples from a defined population. For example, in calculating the probability that, in a group of 20 children, 3 or more have blue eyes, a number of random groups of 20 can be examined. The central limit theorem refers to the fact that sums of large samplings of random, independent variables approximate a normal distribution. The law of large numbers implies that as samplings become larger, observed frequencies of events approach theoretical probabilities.

Probability theory also includes the study of phenomena that evolve randomly in time—as, for example, traffic-flow patterns and waiting lines, or queues. Such an event is called a stochastic process. Recent developments in this field include application of Markov chain theory to computer simulations of "real" events, Markov chains (named for A. A. MARKOV) being stochastic processes that involve only a discrete set of states. Rasch procedures (named for a Danish mathematician, George Rasch) have been used to predict the odds of producing correct answers in psychological tests.

4. Explain the following patterns of heredity.

A. Monohybrid Crosses

B. Dihybrid Crosses

C. Incomplete Dominance

D. Codominance

E. Multiple Alleles

F. Continuos Variation

G. Environmental Influences

A. A cross that provides data about one pair of contrasting traits is called a monohybrid cross. A cross between a pea plant that is true-breeding for tallness and one that is true-breeding for shortness is an example of a monohybrid cross. Biologists can also predict the probable outcome of a cross by using a diagram called a Punnett square, named for its inventor, Reginald Punnett. In the Punnett square of a TT * tt, the genotype of the tall plant and the alleles (TT) it can contribute to its offspring are written, the genotype of the tall plant and the alleles (TT) it can contribute to its offspring are written on the top left side of the square. The genotype of the short plant and the alleles (tt) it can contribute to its offspring are written on the bottom left of the square. The interior of the square is a grid of boxes. Each box is filled with two letter – one letter from the left side of the square and one letter from the top of the square. These letter indicate the possible genotypes of the offspring. In the case of the monohybrid cross, TT * tt, 100% of the offspring are expected to be heterozygous (Tt). Note that by convention, the dominant form of the trait is written first, followed by the lowercase letter for the recessive form of the trait. punnett squares can also be used to predict the outcome of a heterozygous cross. For example, in rabbits the allele for a black coat (B) is dominant over the allele for a brown coat (b). A cross of Bb * Bb, predicts the results of a monohybrid cross between two rabbits that are both heterozygous (Bb) for coat color. As you can see, one-fourth of the offspring would be expected to have the genotype BB, two-fourths (one-half) would be expected to have the genotype Bb, and one-fourth would be expected to have the genotype bb. Since B is dominant over b, three-fourths of the offspring would have a black coat, and one-fourth would have a brown coat. Here you can see the two ratios that Mendel observed in his experiments –1BB:2Bb:1bb (genotype) and 3 black:1 brown (phenotype).

B. A dihybrid cross is a cross that involves two pairs of contrasting traits. Predicting the results of a dihybrid cross is more complicated than predicting the results of a monohybrid cross because you have to consider how the two alleles of each of the two traits from each parent can combine. For example, suppose you want to predict the results of crossing a pea plant that is homozygous for round, yellow seeds (RRYY) with one that is homozygous for wrinkled green seeds (rryy). A RRYY * rryy cross contains 16 boxes. When the alleles from each parent are independently sorted and listed, RY runs along the bottom left side of the Punnett square and ry runs along the top left side. The genotype of all offspring should be RrYy. Therefore, all the offspring should have round, yellow seeds. In guinea pigs the allele for short hair (S) is dominant over the allele for long hair (s), and the allele for black hair (B) is dominant over the allele for brown hair (b). A SsBb * SsBb cross between two individuals heterozygous for both characteristics (SsBb). The offspring are likely to have nine different genotypes that will result in the following four phenotypes:

1. Nine sixteenths (9/16) of the guinea pigs will have short, black hair. These

include individuals with the genotypes SSBB, SsBB, SSBb, and SsBb.

2. Three-sixteenths (3/16) will have short, brown hair. These

include individuals with genotypes SSbb and Ssbb.

3. Three-sixteenths (3/16) will have long, black hair. These

include individuals with the genotypes ssBB and ssBb.

4. One-sixteenth (1/16) will have long, brown hair.

These include individuals with the genotype ssbb.

C. In some organisms, an individual displays a trait that is intermediate between the two parents, a phenomenon known as incomplete dominance. For example, the inheritance of flower color in snapdragons does not follow Mendel’s idea of dominance. A cross between a snapdragon with red flowers and one with white flowers produces a snapdragon with pink flowers. The flowers appear pink because they have less red pigment than the red flowers.

D. In some cases, two dominant alleles are expressed at the same time, a phenomenon called Codominance. Codominance is different from incomplete dominance because both traits are displayed. An example of Codominance is the roan coat in horses. A cross between a homozygous red horse and a homozygous white horse results in heterozygous offspring with a roan coat, which consists of red hairs and white hairs.

E. Some traits have genes with more than two alleles; these are refereed to as multiple alleles. For example, there are three alleles that can determine human blood type – A, B, and O. The A and B alleles are both dominant over O, which is recessive, but neither is dominant over the other. When A and B are both present in the genotype, they are codominant. The existence of these multiple alleles explain why there are four different blood types – A, B, AB, and O.

F. When several genes influence a trait, such as height or weight, determining the effect of one of these genes is difficult, just as it is difficult to follow the flight of one bee within a swarm. Because the genes that determine a phenotype such as height or weight may segregate independently of one another, slight difference in phenotypes are expressed when many individuals are compared. These traits are said to be exhibiting continuos variation because you see a variety of phenotypes on a continuum from one extreme to another.

G. An individual’s phenotype often depends on conditions in the environment. For example, during the winter, the pigment-producing genes of the arctic fox do not function due to the cold temperature. As a result, the coat of the fox is white, and the animal blends into the snowy background. In summer, the genes function to produce pigments and the coat darkens to a reddish brown, resembling the color of the tundra where the fox lives.

5. Describe at least seven disorders caused by genetic changes in humans.

Cystic fibrosis is a genetic disease of childhood characterized by respiratory and digestive problems. It is always fatal; the average life span of its victims is only about 29 years. The disease is the most common inherited disease among Caucasians, and the faulty gene must be inherited from both parents. Cystic fibrosis apparently causes chloride ions to be unable to cross the specialized epithelial cells of salivary, mucus, and sweat glands, and the pancreas. Patients have heavy production of thick mucus in respiratory tracts, which increases susceptibility to respiratory infections; 90 percent of all patients die of chronic lung disease. Secretions that block pancreatic ducts cause important digestive enzymes to fail to reach the small intestine. Treatment is directed toward relief of symptoms, and no cure is yet known. The gene that causes cystic fibrosis was located in 1989. In 1993, a successful treatment to correct the defective gene used inactivated cold viruses to carry corrective genes to cells in the nose. In 1995 researchers found that daily doses of ibuprofen can slow lung deterioration.

Sickle-cell disease, also called sickle-cell anemia, is a group of genetic disorders characterized by an abnormal form of hemoglobin, the oxygen-carrying protein of red BLOOD cells. Offspring of parents who both carry the gene controlling formation of this sickle-cell hemoglobin (HbS) may inherit SS, the most common type of disease. When HbS unloads oxygen, it forms a gel of polymers that causes the red blood cell to become stiff and distorted into sicklelike shapes. these cells break up easily, leading to anemia. They also damage and clog up blood vessels and impede blood flow, leading to tissue damage and dysfunction of internal organs. Pain attacks are the most common symptom. Infections and lung damage are the leading cause of death.

In the United States, sickle-cell disease primarily affects African Americans, but it also occurs in some individuals of Mediterranean, Middle Eastern, and Asian Indian descent. An estimated 60,000 Americans suffer from the disease, and about 2.5 million have the sickle-cell trait (AS) and are healthy carriers of the HbS gene. People with sickle-cell trait do not have the common symptoms of the disease but rarely may have bleeding from the kidney. Prospective parents can be tested to determine if they carry the sickle-cell gene or other related abnormal genes which can lead to SS or other types of sickle-cell disease in offspring.

Treatment is largely symptomatic and includes pain relievers, antibiotics, and blood transfusions. Bone-marrow transplants have been successful in curing the disease, but also have a high degree of risk. Hydroxyurea has been shown to decrease the frequency of pain attacks and need for blood transfusion in adult patients. Studies in children are under way. New drugs are being tested that interfere with the structure of HbS, preventing it from forming polymers. Genetically engineered mice that produce human HbS have been produced. They are currently being used in studying the effects and treatment of the disease.

Tay-Sachs disease is a rare genetic disease in which the lack of the enzyme hexosaminidase A, involved in the metabolism of brain lipids, causes a fatty substance called ganglioside to accumulate in nerve cells of the brain. The disease develops during infancy, primarily in Jewish babies, and leads to blindness, dementia, convulsions, extensive paralysis, and death, usually in 2 to 4 years. The Tay-Sachs gene, carried by 4 percent of American Jews of European heritage, must be present in both parents for the child to develop the disease. Prenatal tests such as amniocentesis and chorionic villus sampling allow detection of the disease before birth.

Phenylketonuria (PKU) is a genetic disease that, if undetected at birth, affects brain maturation and results in mental retardation; however, most cases are identified at birth with a mandatory heel-prick screening test. The disease is caused by defective activity of the enzyme phenylalanine hydroxylase, which results in a higher-than-normal blood level of the amino acid phenylalanine. An infant identified with PKU is placed on a special low-protein, formula-based diet that severely limits phenylalanine intake and allows normal, healthy development. The child stays on this diet through adolescence, and in some cases into adulthood. Women with PKU must stay on the restrictive diet when pregnant, since abnormal amounts of phenylalanine can injure a fetus. If left untreated, accumulation of this amino acid can produce neurological problems that prevent walking and talking, seizures, and extreme hyperactivity. The IQ of an untreated child with PKU rarely rises above 70. The incidence of PKU in the United States is about 1 in 14,000 births. One person in 60 carries one gene for PKU, and the child of two carriers has a 25-percent chance of developing the disease. In 1983 a genetic-marker technique was introduced to detect carriers and affected fetuses in families that have a history of PKU.

Hemophilia is a sex-linked genetic disease that results in deficient blood coagulation. The disease causes excessive bleeding, which occurs spontaneously or upon slight injury; bleeding may be external or internal in joints, the abdominal cavity, the brain, and other organs. If untreated, some bleeding episodes can be fatal.

In normal blood coagulation, or clotting, a complex interaction of plasma proteins, called clotting factor, results in a gelatinous, fibrillar plug that seals leaks in damaged blood vessels. One of these plasma proteins, factor VIII, is lacking in persons with hemophilia A (the most common form), retarding the clotting process. The second most common form, hemophilia B, called Christmas disease, occurs when factor IX is lacking.

The gene for hemophilia is located on the female sex (X) chromosome. Females have two X chromosomes; males have an X and a Y chromosome, the latter containing little genetic information. Although the hemophilia gene is recessive, males who inherit the gene on their X chromosome have the disease. Females with the hemophilia gene on one X chromosome and a normal gene on the other can transmit the disease to their male offspring but do not get the disease. Each daughter of a carrier mother has a 50 percent chance of being a carrier, and each son has a 50 percent chance of having hemophilia. Although affected males cannot transmit the disease to their sons, their daughters will inherit the gene and be carriers. Genetic tests for most kinds of hemophilia now exist, and hemophilia A can usually be determined before birth.

Before 1965 hemophilia was treated with transfusions of whole blood or freshly frozen plasma. In 1965 a plasma extract called cryoprecipitate became available. By the early 1970s clotting factor became available in freeze-dried or concentrated form, allowing people with hemophilia to administer their treatment at home. However, the clotting factor was derived from the blood of many donors, which led to its contamination with HIV virus. Between 1979 and 1985, more than 60 percent of all people with hemophilia were infected with HIV; the rate of transmission to sexual partners was about 12 percent. Since 1987 no persons with hemophilia have become HIV-positive from clotting factor. Blood donors are screened for risk of HIV, blood is tested for the virus, and blood products are virally inactivated.

Huntington's disease is a hereditary genetic disorder affecting about 1 in every 10,000 persons. The disease develops slowly, with subtle symptoms of slurred speech or unsteady gait often appearing first. Eventually, the early symptoms worsen, and there is a progressive deterioration of mental functioning. Brain damage takes place in the basal ganglia of the cerebrum. Nerve cells die, and two neurotransmitters that the cells produce are depleted in the brain. At the same time, an excess of another neurotransmitter, dopamine, builds up in the basal ganglia. The damage causes alternating periods of excitement and depression, sometimes misdiagnosed as schizophrenia.

If one parent of a child has Huntington's disease and the other does not, the child has a 50 percent chance of inheriting the disease. Once transmitted, it is certain to develop. The first symptoms usually appear between the ages of 35 and 55, but earlier and later occurrences are known. The disease may progress for 10 to 20 years, until the patient dies.

No treatment yet exists for Huntington's disease. Genetic markers, identifiable segments of the DNA molecule that can be used as indicators of the presence of the gene, were discovered in 1983. This enabled researchers to develop a test for people at risk of developing the disease, using the markers and blood samples from many family members, to determine the likely presence of the gene. The markers also enabled researchers to focus on a particular location in searching for the gene. In 1993 researchers located the gene for Huntington's disease. The gene is what is called a "stuttering" gene, one that has a varying number of extra repeats of a protein sequence; this type of gene also causes conditions such as fragile x syndrome . These repeats also play a role in age of onset and severity; the more repeats, the worse the disease and the earlier onset. This finding also makes available a direct blood test for people at risk of developing the disease.

Muscular dystrophy is a term that encompasses several hereditary diseases characterized by progressive weakness and degeneration of skeletal muscle. The most common form was described by the French neurologist Guillaume B. A. Duchenne in 1868. Duchenne muscular dystrophy is inherited as a recessive disorder, the gene for which is carried on the X chromosome. As a result, like hemophilia, the disease is sex-linked, affecting males. Symptoms of weakness begin in early childhood. The muscles--especially those of the calves--become abnormally enlarged. This is partially caused by infiltration of the muscles with fat. Progressive destruction of muscle leads to a wheelchair existence, usually by age 13. Death usually occurs by the late twenties. Female carriers can be detected in many instances by a simple blood test that measures an enzyme known as creatine kinase, and in 1985 detection also became possible through tests for genetic markers indicating the presence of the Duchenne gene. The location of the large gene on the X chromosome was determined in 1986. Before the twentieth gestational week, pregnancies at risk for the disease can be monitored by analyzing fetal blood.

Other forms of muscular dystrophy follow various patterns of inheritance and may affect children and adults of both sexes. Some are less severe and less progressive than the Duchenne form. No cure exists as yet for any form of the disease. In 1987 researchers identified a protein that the abnormal Duchenne gene produces in abnormal form or not at all, and named this protein dystrophin. The protein was later located in the outer membrane of normal muscles. A lack of the protein was shown to lead to Duchenne and other forms of the disease. A therapy developed in 1990 involves transplanting healthy cells into a muscle of a patient with the disease. Early results show that the healthy cells begin making dystrophin and aid in improving muscle weakness. The Muscular Dystrophy Association of America and its affiliated organizations worldwide sponsor research and scientific meetings aimed at learning the cause and treatment of muscular dystrophy.