A. Mutations

1. Changes in chromosomes or genes that pass to offspring if they occur in gametes.
        2. Mutations increase the amount of variation among offspring.
        3. Chromosomal mutations include changes in chromosome number and structure.

B. Changes in Chromosomal Structure

1. Environmental factors including radiation, chemicals, and viruses, can cause chromosomes to break; if the broken ends do not rejoin in the same pattern, this causes a change in chromosomal structure.
2. Inversion: a segment that has become separated from the chromosome is reinserted at the same place but in reverse; the position and sequence of genes are altered.

3. Translocation: a chromosomal segment is removed from one chromosome and inserted into another, nonhomologous chromosome. Translocation heterozygotes usually have reduced fertility due to production of abnormal gametes.

4. A deletion is a type of mutation in which an end of a chromosome breaks off or when two simultaneous breaks lead to the loss of a segment.
a. Even if only one member of pair of chromosomes is affected, a deletion can cause abnormalities.

b. Cri du chat syndrome is deletion in which an individual has a small head, is mentally retarded, has facial abnormalities, and abnormal glottis and larynx resulting in a cry resembling that of a cat.

5. A duplication is a doubling of a chromosomal segment.
            a. A broken segment from one chromosome can simply attach to its homologue.
            b. Unequal crossing-over may occur.

6. Multiple copies of genes can mutate differently and provide additional genetic variation for a species.

        1. Human somatic (body) cells have 22 pairs of autosomes, one pair of sex chromosomes; total of 46.
        2. Karyotypes show chromosomes paired according to size, shape, and appearance in metaphase.
            a. To view chromosomes, cells are treated and photographed just prior to dividing.
            b. Chromosomes are then sorted and arranged by homologous pairs, often by computer imaging.
            c. Members of a pair have the same size, shape, and banding pattern.
            d. Chromosomes in a karyotype are aligned from largest to smallest.
            e. A karyotype can be used to diagnose chromosomal abnormalities.
        3. Sex chromosomes of a normal male are X and Y; a normal female has two X chromosomes.
        4. All chromosomes besides X and Y are autosomes.
        5. To view chromosomes of an unborn child, cells must be sampled from an embryo.

A. Predicting Offspring

1. Genetic disorders are medical conditions caused by alleles inherited from parents.
2. Males are designated by squares, females by circles; shaded circles and squares are affected individuals; line between square and circle represents a union; vertical line leads to offspring.
3. A carrier is a heterozygous individual who has no apparent abnormality but can pass on an allele for a recessively inherited genetic disorder.
4. Autosomal dominant and autosomal recessive alleles have different patterns of inheritance.
            a. Characteristics of autosomal dominant disorders
1) Affected children usually have an affected parent.
                2) Heterozygotes are affected. Two affected parents can produce unaffected child; two unaffected parents will not have affected children.
            b. Characteristics of autosomal recessive disorders
                1) Most affected children have normal parents since heterozygotes have a normal phenotype.
                2) Two affected parents always produce and affected child.
                3) Close relatives who reproduce together are more likely to have affected children.
5. Chance has no memory; each child born to heterozygous parents has a 25% chance of having a disorder
regardless of prior siblings' conditions.

Pedigrees help on studying how traits are passed on from generation to generation.

Dominant Disorders

1. Huntington Disease
            a. This is also an autosomal dominant disorder that affects one in 20,000 people.
            b. It leads to progressive degeneration of brain cells, which in turn causes severe muscle spasm,
                personality disorders, and death in 10 -15 years from onset.
            c. Most appear normal until they are of middle age and already have had children who might carry
                the gene; occasionally, first signs of the disease are seen in teenagers or even younger.
            d. The gene for Huntington disease is located on chromosome 4.
            e. Apparently, persons most at risk are those inheriting the gene from their fathers.

2. Achondroplasia – dwarfism

3. Hypercholesterolemia –excess cholesterol in blood; heart disease

1. Cystic Fibrosis
            a. This is most common lethal genetic disease in Caucasians in U.S.
            b. About 1 in 20 Caucasians is a carrier, and about 1 in 2,500 births has this disorder.
            c. Involves production of viscous form of mucus in the lungs and pancreatic ducts.
                1) Resultant accumulation of mucus in the respiratory tract interferes with gas exchange.
                2) Digestive enzymes must be mixed with food to supplant the pancreatic juices.
            d. New treatments have raised average life expectancy to 17-28 years.
            e. Chloride ions (Cl-) fail to pass plasma membrane proteins.
            f. Since water normally follows Cl-, lack of water in the lungs causes thick mucus.
            g. Cause is mutated gene on chromosome 7; attempt to insert gene into nasal epithelium has had
                limited success and restores about 25% of Cl- ion transport ability.
            h. Genetic testing for adult carriers and fetuses is possible.
  2. Tay-Sachs Disease
            a. Usually occurs among Jewish people in the U.S. of central and eastern European descent.
            b. Symptoms are not initially apparent; infant's development begins to slow at 48 months, neurological
                and psychomotor difficulties become apparent, child gradually becomes blind and helpless, develops
                seizures, eventually becomes paralyzed, dies by age of three or four.
            c. Results from lack of enzyme hexosaminidase A (Hex A) and subsequent storage of its substrate,
                glycosphingolipid, in lysosomes.
            d. Primary sites of storage are cells of the brain; accounts for progressive deterioration.
            e. No treatment or cure; prenatal diagnosis is by amniocentesis and chorionic villi sampling.
  3. Phenylketonuria (PKU)
            a. PKU occurs 1 in every 5,000 births; it is most common inherited disease of nervous system.
            b. Lack of enzyme needed to metabolize amino acid phenylalanine results in accumulation of the amino
                acid in nerve cells of the brain; this impairs nervous system development.
            c. PKU is caused by a mutated gene on chromosome 12.
            d. Now newborns are routinely tested in hospital for high levels of phenylalanine in the blood.
            e. If infant has PKU, child is placed on diet low in phenylalanine until brain is fully developed near age

4. Albinism – no pigment in skin, hair and eyes

5. Galactosemia – accumulation of galactose in tissues, leads to mental retardation and liver damage

Sickle-cell disease is a blood disorder controlled by incompletely dominant alleles.
            a. Codominance occurs when alleles are equally expressed in a heterozygote.
            b. HbA HbA individuals are normal; HbS HbS have sickle-cell trait. The allele for normal hemoglobin (H^A) is codominant to the sickle cell allele (H^S)

            c. With sickle-cell disease, red blood cells are irregular in shape (sickle-shaped) rather than biconcave,
                due to abnormal hemoglobin that the cells contain.
            d. Due to irregular shape, sickle-shaped red blood cells clog vessels and break down; results in poor
                circulation, anemia, low resistance to infection, hemorrhaging, damage to organs, jaundice, and pain
                of abdomen and joints.
            e. Persons heterozygous for sickle-cell (HbAHbS) are usually asymptomatic unless stressed.

f. Bone marrow transplants pose high risks; other research focuses on fetal hemoglobin, etc.
            g. In malaria regions of Africa, infants heterozygous (HbAHbS) for sickle-cell allele have better chance of surviving; malaria parasite dies as potassium leaks from sickled cells. 1 every 500 African American. It is more common on African descendent people (10% of African American, and as many as 40% of African). Why is this trait so common on those particular populations? People who are carriers for sickle cell are resistant to malaria – better chance of survival!

Mendelism and Chromosomes

A. Chromosomal Theory of Inheritance

        1. Genes are located on chromosomes; behavior of chromosomes during mitosis was described in
            1875 and for meiosis, in 1890's.
        2. Chromosome theory independently proposed in 1902 by Theodor Boveri and Walter S. Sutton.
        3. Accounts for the similarity of chromosomal behavior during meiosis and fertilization.
        4. Theory is supported by the following observations:
            a. Both chromosomes and factors (now called alleles) are paired in diploid cells.
            b. Chromosomes and alleles of each pair separate during meiosis so gametes have one-half.
            c. Chromosomes and alleles of separate independently; gametes contain all combinations.
            d. Fertilization restores diploid chromosome number and paired condition for alleles in zygote.

B. Sex Chromosomes

        1. In most animal species, chromosomes can be categorized as two types:
            a. Autosomes are non-sex chromosomes that are the same number and kind between sexes.
            b. Sex chromosomes determine if the individual is male or female.
        2. Sex chromosomes in the human female are XX; those of the male are XY.
        3. Males produce X-containing and Y-containing gametes; therefore males determine the sex of offspring.
        4. Besides genes that determine sex, sex chromosomes carry many genes for traits unrelated to sex.
        5. X-linked gene is any gene located on X chromosome; used to describe genes on X chromosome that
            are missing on the Y chromosome.

C. X-Linked Alleles

** Thomas Hunt Morgan American geneticist of the early 1900’s.

        1. Work with fruit flies by Thomas Hunt Morgan (Columbia University) confirmed genes were on chromosomes.
            a. Fruit flies are cheaply raised in common laboratory glassware.
            b. Females only mate once and lay hundreds of eggs.
            c. Fruit fly generation time is short, allowing rapid experiments.
        2. Experiments involved fruit flies with XY system similar to human system.
            a. Newly discovered mutant male fruit fly had white eyes.
            b. Cross of white-eyed male with dominant red-eyed female yield expected 3:1 red-to-white ratio;
                however, all white-eyed flies were males!
            c. An allele for eye color on the X but not Y chromosome supports the results of the cross.
            d. Behavior of allele corresponds to chromosome, confirming chromosomal theory of inheritance.
        3. X-Linked Problems
            a. X-linked alleles are designated as superscripts to X chromosome.
            b. Heterozygous females are carriers; they do not show the trait but can pass it on.
            c. Males are never carriers but express the one allele on the X chromosome.
            d. One form of color-blindness is X-linked recessive.

Sex-linked Genetic Disorders

A. Sex Chromosomes

        1. Traits controlled by alleles on sex chromosomes are sex-linked.
        2. Since Y chromosome is smaller, most sex-linked genes are on the X chromosome.

B. X-Linked Recessive Disorders

        1. Males receive X-linked traits from mother, source of male's only X chromosome.
        2. If female shows a recessive sex-linked trait, her father must have it and her mother is carrier.

C. Thomas Hunt Morgan studied sex-linked traits in fruit flies (Drosophila)

 

		White eyed male (Xr Y)
		Xr	Y
XR	XR Xr	XR Y
XR	XR Xr	XR Y

F1 = 2 male and 2 females red eyed

 

		Red eyed male (XR Y)
		XR	Y
XR	XR XR	XR Y
Xr	XR Xr	Xr Y

F2 = 2 female red eyed, 1 male red eyed, 1 male white eyed

Every time this experiment was run, the male only came up with white eyes.

To make sure that this was a sex-linked gene Morgan cross a white-eyed male with a red-eyed female from the F1 generation (X^R X^r):

 

		White eyed male (Xr Y)
		Xr	Y
XR	XR Xr	XR Y
Xr	Xr Xr	Xr Y

1 male and female red eyed, 1 male and female white-eyed

D. Some Disorders Are X-Linked

        1. Color Blindness
  a. Can X-linked recessive disorder involving mutations of genes coding for green or red sensitive cone cells, resulting in inability to perceive green or red, respectively.
       b. The possible genotypes for color blindness are as follows:
                1) X^C X^C = a female who has normal color vision;
                2) X^CX^c = a carrier female who has normal color vision;
                3) X^cX^c = a female who is color blind;
                4) X^CY = a male who has normal color vision; and
                5) X^cY = a male who is color blind.

 

		Colorblind male (Xc Y)
		Xc	Y
XC	XC Xc	XC Y
XC	XC Xc	XC Y

ALL NORMAL

 

		Normal male (XC Y)
		XC	Y
XC	XC XC	XC Y
Xc	XC Xc	Xc Y

1 male colorblinded

        2. Duchenne Muscular Dystrophy
a. Duchenne muscular dystrophy is most common form; characterized by wasting away of muscles, eventually leading to death; it affects one out of every 3,600 male births.
b. X-linked recessive disease involves a mutant gene that fails to produce protein dystrophin.
c. Symptoms (e.g., waddling gait, toe walking, frequent falls, difficulty in rising) soon appear.
d. Muscle weakens until individual is confined to wheelchair; death usually occurs by age 20.
e. Affected males are rarely fathers; the gene passes from carrier mother to carrier daughter.
f. Lack of dystrophin caused calcium ions to leak into muscle cells; this promotes action of an enzyme that dissolves muscle fibers.
g. As body attempts to repair tissue, fibrous tissue forms and cuts off blood supply.
h. Test detects carriers of Duchenne muscular dystrophy; treatments are under research.
        3. Hemophilia
a. About one in 10,000 males is a hemophiliac with impaired ability of blood to clot.

b. Hemophilia has two types: Hemophilia A is due to absence of clotting factor IX; Hemophilia B is due to absence of clotting factor VIII.
c. Hemophiliacs bleed externally after an injury and also suffer internal bleeding around joints.
d. Hemorrhages stop with transfusions of blood (or plasma) or concentrates of clotting protein.
e. Hemophiliacs were at high risk of AIDS if receiving blood or using blood concentrate to replace clotting factors.

f. Factor VIII is now available as a genetic engineering product.
g. Of Queen Victoria's 26 offspring, 5 grandsons had hemophilia, 4 granddaughters were carriers.

 

		Male with hemophilia (Xh Y)
		Xh	Y
XH	XH Xh	XH Y
XH	XH Xh	XH Y

ALL NORMAL

 

		Normal male (XH Y)
		XH	Y
XH	XH Xh	XH Y
Xh	XH Xh	Xh Y

1 male with hemophilia

E. Some Traits are Sex-influenced

        1. Some genes not located on the X or Y chromosome are expressed differently in the two sexes.
        2. Male pattern baldness is caused by an autosomal allele that is dominant in males and due to presence of testosterone.

F. Changes in Chromosome Number

1. Monosomy occurs when and individual has only one of a particular type of chromosome.
2. Trisomy occurs when and individual has three of a particular type of chromosome.
3. Nondisjunction is the failure of chromosomes to separate; it is more common during meiosis I than meiosis II; it can occur in mitosis.
4. Monosomy and trisomy occur in plants and animals; in autosomes of animals, it is generally lethal.
5. Nonlethal human monosomies and trisomies include the following:

a. Turner (XO) syndrome: monosomy where females have only one sex chromosome, and X. Turner females are short, have broad chest and webbed neck. Ovaries of Turner females never become functional; therefore, do not undergo puberty.   

b. Down syndrome is most common autosomal trisomy, involves chromosome 21.
Most often, Down syndrome results in three copies of chromosome 21 due to nondisjunction during gametogenesis. In 23% of cases, the sperm had the extra chromosome 21. In 5% of cases, there is translocation with chromosome 21 attached to chromosome 14; this translocation could have occurred generations earlier and is not age-related. Chances of a woman having Down syndrome child increase with age. Chorionic villi sampling testing or amniocentesis and karyotyping detects a Down syndrome child. Down syndrome child has tendency for leukemia, cataracts, faster aging, and mental retardation. Gart gene, located on bottom third of chromosome 21, leads to high level of purines and is associated with mental retardation; future research may lead to suppression of this gene.

c. Klinefelter syndrome males have one Y chromosome and two or more X chromosomes. Affected individuals are sterile males; testes and prostate are underdeveloped. Individuals have large hands and feet and long arms and legs.

d. Triplo-X females have three or more X chromosomes. There is no increased femininity; most lack any physical abnormalities. There is an increased risk of having triplo-X daughters of XXY sons. May experience menstrual irregularities, including early onset of menopause.
e. XYY males with Jacob syndrome have two Y-chromosomes instead of one. Results from nondisjunction during meiosis II. Usually taller than average; suffer from persistent acne; tend to have lower intelligence. Earlier claims that XYY individuals were likely to be aggressive are not correct.
6. Polyploidy: offspring end up with more than two complete sets of chromosomes.
a. Terms indicate how many sets of chromosomes are present (triploids [3n], tetraploids [4n]).
b. Polyploidy does not increase variation in animals; judging from trisomies, it would be lethal.
c. Polyploidy is a major evolutionary mechanism in plants; probably involved in 47% of flowering plants including major crops.
d. Hybridization in plants can result in doubled number of chromosomes; an even number of chromosomes can undergo synapsis during meiosis; successful polyploidy results in a new species.

The Human Genome

A. The Human Genome Project will map the location of human genes on all chromosomes.

        1. Initial funding was by the U.S. government; increasingly funded by pharmaceutical industry.
B. Second goal is to construct a base sequence map of the 3 billion base pairs in human genome.

        1. This would require 200 volumes with 1,000 pages per volume to write out.
        2. Anticipated completion date: 2004

Chorionic villus biopsy is the removal of embryotic cells directly from the embryo. Faster results. It is linked with some birth defects if test is done before the 10 week of pregnancy.

Amniocentesis is the removal of a small amount of liquid from the sac surrounding the embryo. The cells are harvest and a karyotype is made to display the chromosomes. Today, more than 100 genetic disorders can be detected using this technique.

Ultrasound Ultrasounds are used to detect: number of fetuses; any enlargement or underdevelopment of the fetus’s organs; the size of the fetus

 

Analyzing DNA

1. An entire genome of an individual can be subjected to DNA fingerprinting.
2. DNA fingerprinting is the technique of using DNA fragments lengths, resulting from restriction enzyme cleavage, to identify particular individuals.
            a. DNA is treated with restriction enzymes to cut it into fragments.
            b. Each organism's DNA results in different-sized restriction fragment length polymorphisms (RFLP's).
            c. During gel electrophoresis, fragments separate according to length, resulting in a pattern of bands.
            d. Radioactive probes allow specific sequences to be separated from all other fragments, and the resulting pattern to be recorded on X-ray film (autoradiography).
            e. DNA fingerprinting can identify deceased individuals from skeletal remains, perpetrators of crimes from blood or semen samples, and genetic makeup of long-dead individuals or extinct organisms

Here's a look at one DNA testing procedure:
1. Evidence: DNA is extracted from blood, hair, semen or other body tissue.
2. Fragmentation: Using an enzyme, scientists cut the DNA into fragments. The fragments vary in length depending on an individual's genetic code.
3. Separation: The fragments are placed in a tray containing special gel. An electrical current pulls the fragments along the gel. Heavier fragments move a short distance; lighter fragments go farther. As a result, the fragments may be separated according to size.
4. X-ray: The separated DNA is transfered to a nylon membrane and radioactively treated. Radiactive genetic material or "probes" search out and lock onto various parts of the DNA. An X-ray is made of the fragment patterns on the membrane.
5. Autorad: The X-ray, called an autoradiograph or autorad, is developed, producing a pattern of bands that look like a bar code. This DNA "fingerprint" is compared with others for matches.

Genes, which are carried on chromosomes, are the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions on how to make proteins. Although genes get a lot of attention, it’s the proteins that perform most life functions and even make up the majority of cellular structures. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result.

Gene therapy is a technique for correcting defective genes responsible for disease development. Researchers may use one of several approaches for correcting faulty genes:

A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common.

An abnormal gene could be swapped for a normal gene through homologous recombination.

The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function.

The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.

In most gene therapy studies, a "normal" gene is inserted into the genome to replace an "abnormal," disease-causing gene. A carrier molecule called a vector must be used to deliver the therapeutic gene to the patient's target cells. Currently, the most common vector is a virus that has been genetically altered to carry normal human DNA. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes.

Target cells such as the patient's liver or lung cells are infected with the viral vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state.

Besides virus-mediated gene-delivery systems, there are several nonviral options for gene delivery. The simplest method is the direct introduction of therapeutic DNA into target cells. This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA. Another nonviral approach involves the creation of an artificial lipid sphere with an aqueous core. This liposome, which carries the therapeutic DNA, is capable of passing the DNA through the target cell's membrane.

Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This chromosome would exist autonomously alongside the standard 46 --not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the body's immune systems would not attack it. A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell.

The Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale. Current gene therapy is experimental and has not proven very successful in clinical trials. Little progress has been made since the first gene therapy clinical trial began in 1990. In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger. Jesse was participating in a gene therapy trial for ornithine transcarboxylase deficiency (OTCD). He died from multiple organ failures 4 days after starting the treatment. His death is believed to have been triggered by a severe immune response to the adenovirus carrier.

Another major blow came in January 2003, when the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. FDA took this action after it learned that a second child treated in a French gene therapy trial had developed a leukemia-like condition. Both this child and another who had developed a similar condition in August 2002 had been successfully treated by gene therapy for X-linked severe combined immunodeficiency disease (X-SCID), also known as "bubble baby syndrome."

University of California, Los Angeles, research team gets genes into the brain using liposomes coated in a polymer call polyethylene glycol (PEG). The transfer of genes into the brain is a significant achievement because viral vectors are too big to get across the "blood-brain barrier." This method has potential for treating Parkinson's disease.

RNA interference or gene silencing may be a new way to treat Huntington's. Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced. See Gene therapy may switch off Huntington's at NewScientist.com (March 13, 2003).

New gene therapy approach repairs errors in messenger RNA derived from defective genes. Technique has potential to treat the blood disorder thalassaemia, cystic fibrosis, and some cancers. See Subtle gene therapy tackles blood disorder at NewScientist.com (October 11, 2002).

Gene therapy for treating children with X-SCID (sever combined immunodeficiency) or the "bubble boy" disease is stopped in France when the treatment causes leukemia in one of the patients. See 'Miracle' gene therapy trial halted at NewScientist.com (October 3, 2002).

Sickle cell is successfully treated in mice. See Murine Gene Therapy Corrects Symptoms of Sickle Cell Disease from March 18, 2002, issue of The Scientist.

What is normal and what is a disability or disorder, and who decides? Scientists? Government? Community?

How shall we decide which genes should be transplanted and altered?

Who shall determine whether experiments with genetic engineering should be done?

Are disabilities diseases? Do they need to be cured or prevented?

Does searching for a cure demean the lives of individuals presently affected by disabilities?

Is somatic gene therapy (which is done in the adult cells of persons known to have the disease) more or less ethical than germline gene therapy (which is done in egg and sperm cells and prevents the trait from being passed on to further generations)? In cases of somatic gene therapy, the procedure may have to be repeated in future generations.

Preliminary attempts at gene therapy are exorbitantly expensive. Who will have access to these therapies? Who will pay for their use?

If human cells can be manipulated in this way, should we try to engineer taller people or change the eye color, hair, sex, and blood type?

How should parent react, today, to the news that their child might be born with a serious or fatal genetic disorder?

The answer to such questions cannot be answer by science but only by the human spirit!

Breeding Strategies

o Because we are not satisfied with the world around us, we are always trying to "improve it". By selecting the most productive plants or animals we can produce the next generation with more productivity.

o Selective breeding: the oldest way of improving a species. L. Burbank was the most famous selective breeder (250 new fruits, potato, flower). A few individuals are selected to be the parents according to wanted characteristics. Use to improve yield of a crop, increase milk production, flower color.

· Inbreeding: is used to maintain a stock of similar organisms. Risks: chances of receiving recessive genetic defects.

· Hybridization: involves the crossing of members of different (but related) species. All commercial corns are hybrids.

Biotechnology Products

        1. Genetically engineered organisms can produce biotechnology products.
        2. Free-living organisms that have had a foreign gene inserted into them are transgenic.

A. Transgenic Bacteria

        1. Bacteria are grown in large vats.
            a. When foreign genes are inserted, much product can be harvested.
            b. Products on the market include: insulin, hepatitis B vaccine, t-PA and human growth hormone.
        2. Transgenic bacteria have been produced to protect and improve the health of plants.
            a. Frost-minus bacteria protect the vegetative parts of plants from frost damage.
            b. Root-colonizing bacteria receive genes from bacteria with insect toxin, protecting the roots.
            c. Bacteria that colonize corn roots can be endowed with genes for insect toxin.
        3. Transgenic bacteria degrade substances.
            a. Bacteria selected for ability to degrade oil can be improved by genetic engineering.
            b. Bacteria can be bio-filters to prevent airborne chemical pollutants from being vented into the air.
            c. Bacteria can also remove sulfur from coal before it is burned and help clean up toxic dumps.
        4. Transgenic bacteria produce chemical products.
            a. We can manipulate genes coding for enzymes to catalyze synthesis of valuable chemicals.
            b. Phenylalanine used in aspartame sweetener can be grown by engineered bacteria.
        5. Transgenic bacteria process minerals.
            a. Many major mining companies already use bacteria to obtain various metals.
            b. Genetically engineered "bio-leaching" bacteria extract copper, uranium, gold from low-grade ore.

B. Transgenic Plants

        1. Plant cells that have had the cell wall removed are called protoplasts.
        2. Electric current makes tiny holes in a plasma membrane through which genetic material enters.
        3. Foreign genes now give cotton, corn and potato strains ability to produce insects toxin.
        4. In 1999, 70 million acres were planted to transgenic crops; this will triple in five years.
        5. Transgenic improvements in wheat and rice will be needed to avoid food shortages in 2020.
        6. Stomata leaf openings could be altered to boost CO2 intake or reduce water loss.
        7. Introducing C4 cycle into rice would increase photosynthetic efficiency.
        8. Mouse-eared cress has been engineered to produce a biodegradable plastic in cell granules.
        9. Plant-produced human hormones would be cheap and lack pathogens that could infect people.

C. Transgenic Animals

        1. Animal use requires methods to insert genes into eggs of animals.
            a. It is possible to micro-inject foreign genes into eggs by hand.
            b. Using this technique, many types of animal eggs have been injected with bovine growth hormone (bGH) to produce larger fishes, cows, pigs, rabbits, and sheep.
        2. Gene pharming is the use of transgenic farm animals to produce pharmaceuticals; the product is obtainable from the milk of females.
            a. Genes for therapeutic proteins are inserted into animal's DNA; animal's milk produces proteins.
            b. Drugs obtained through gene pharming are planned for the treatment of cystic fibrosis, cancer, blood diseases, and other disorders.
            c. Testing is underway for antithrombin III to prevent blood clots during surgery.
            d. Producing the gene product in urine instead of milk uses whole herd from birth and it is easier to extract proteins from urine.

D. Cloning Transgenic Animals

        1. Sexual reproduction dilutes the genes of a genetically-altered animal; asexual reproduction only uses the genes of the parent.
        2. Cloning of mammals involves injecting a 2n nucleus adult cell into a enucleated egg.
        3. Cloning of humans violates a Presidential order in the U.S. but may be done elsewhere.

See article about the religious and ethical debates!