Germ Line Cells: Cells that divide to produce eggs in females and sperm in males

Somatic Cells: Cells making up the body and which are usually diploid, that is, they have two sets of genes.

See Fig. 13.2.

Only the germ line cells pass their genes to the next generation. You are descendants of your parents germ line cells, which are haploid.

A somatic cell that gets a mutation early in development will pass the defect on to its descendant cells. Fig. 13.3.

The most important mutations of somatic cells are those that damage the regulatory system controlling cell growth and division. This disruption leads to cancer. See chapter 14.

Recessive Gene: Defective copy of a gene whose properties are not observed because they are masked by a functional copy.

Usually, the detrimental mutation is recessive to the wild type. The single good copy is enough for normal function.

Homozygous: Having two identical alleles of the same gene.

An allele is a particular version of a gene, that is, a particular nucleic acid sequence.

Children from offspring of close relatives have a much higher chance of being homozygous for a hereditary mutation in two recessive genes, and therefore, of expressing this defect. Fig. 13.5.

Fig 13.6. shows the standard symbols for a family tree.

Table 13.1 lists some of the genetic diseases due to a defect of a single gene.

They are either recessive or sex-linked. The recessive ones require both copies of the gene to be defective. The sex-linked ones have the defect on the X chromosome with no corresponding gene on the Y chromosome. In either case, there is no wild type gene to code for the correct protein.

Some are due to interactions of several defective genes: cleft palate, spina bifida, diabetes, some cancers

Others are due to an extra copy of an entire chromosome.

Down Syndrome: Defective development, including mental retardation, resulting from an extra copy of chromosome No. 21.

Extra sex chromosomes are found in about one in 1000 people. Three most common: XXY, XYY, XXX.

Cystic Fibrosis: A disease whose major symptom is the accumulation of fibrous tissue in the lungs.

About 1 in 2000 white children have it.

It is due to a homozygous recessive mutation. Thus, you must inherit a defective copy of the gene from each parent to get the disease.

Carriers: Individuals who have a single defective copy of a gene but who show no clinical symptoms. You can be a carrier for cystic fibrosis but not have symptoms.

See Fig. 13.8 for inheritance pattern.

In cystic fibrosis there is a mutation in the gene that codes for the chloride ion transport protein (Fig. 13.9). The protein does not allow chloride to get into the extracellular space which then does not have enough water. The mucus gets thick. this causes obstruction, infection and scar tissue formation.

The cf gene is on chromosome 7, on the q arm. Only about 2% of the gene is actual coding DNA. See Fig. 13.10.

p arm: The shorter of the two arms of a chromosome.

q arm: The longer of the two arms of a chromosome.

In about 70% of those with cf, there is a deletion of the three bases which code for amino acid no. 508, phenylalanine. The lack results in an abnormal folding of the protein. Figs. 13.11, 13.12. Phosphate must bind to particular site on the protein to allow it to open.

Duchenne Muscular Dystrophy (DMD): One particular form of muscular dystrophy, a group of degenerative muscle diseases.

DMD is sex-linked. See Figs. 13.13, 13.14. If you have a defective gene on a certain portion of the X chromosome of an XY pair, no corresponding gene exists on the Y portion: there is no backup, and symptoms will result.

XX: female

XY: male

YY: you don't exist

dmd gene: Gene which, when defective, causes Duchenne Muscular Dystrophy. Less than one percent of the bases on the dmd gene code for the protein. The protein that is made from the dmd gene is called dystrophin and is large, 4000 amino acids, 10 times as large as the average protein. In most victims the defect is due to alteration of one or a few bases. In about 10%, a chunk of the gene is deleted.

About 2/3's of those with DMD inherit the disease from their mothers and the other 1/3 get it as a result of a new mutation.

One patient had a large enough chunk of DNA deleted to locate the region of the dmd gene under a light microscope. It is located on the P arm of chromosome 15. See Fig. 13.15.

We can do more than counseling. Someone with a family history of cystic fibrosis can be tested to see whether they have the defective gene.

Testing for high-risk diseases can be done for more and more genes.

General approach is to use a hybridization probe or PCR analysis. This will reveal whether a mutant copy of the gene is present.

If both parents test positive for a recessive gene, they can decide whether to try to have children. One in four of their children would get the disease, on average.

Embryos can be examined by drawing amniotic fluid, which contain a few cells from the fetus.

Genetic Engineering: Alteration of an organism by deliberately changing its DNA. The changes will then be inherited.

Gene therapy: The genes are altered in only a body part. Also called genetic surgery. In cystic fibrosis, a wild-type gene can be introduced into the lungs. These changes are not inherited. The person still has defective genes in their germ cells.

Human genetic engineering has not been performed. Genetic engineering has been done on plants and animals, however.

Transgenic Animal or Plant: Individual into which genes from another species have been incorporated. Transgenic animals, ie. transgenic mice, are used in research.

Eugenics: Improving a species by genetic technology. Early human eugenics were based on picking "superior parents."

Napoleonic Wars: Napoleon selected tall men for his army. They had a very high casualty rate. The average height of the French nation decreased significantly in that period.

If we have identified a gene defect and have cloned a good copy of that gene, how to we get it into the body to do its work?

Put the gene into a vector - usually a retrovirus or an adenovirus. Fig. 13.24.

Retroviruses: Class of virus that contains RNA but can convert it back to DNA after infecting the host cell.

Adenoviruses: Class of virus containing DNA that infects many animals.

Lungs are exposed and easy to get at.

The healthy version of the cystic fibrosis gene has been cloned and inserted into a crippled adenovirus (Fig. 13.25). This virus attacks the lining of the respiratory tract and causes colds.

This has been tested in rats and people and has resulted in normal chloride ion movement in some cases.

Mutations in the ada gene cause severe combined immuno-deficiency (SCID): Immune defect due to lack of T- and B- cells. About 20% of inherited SCID cases are due to adenosine deaminase deficiency. Children with SCID must be kept in plastic bubbles. Even a cold can be fatal.

Adenosine Deaminase: An enzyme that converts adenosine to inosine. Its absence indirectly causes a lack of immune T- and B- cells. These are blood lymphocytes which carry out immune surveillance.

Bone narrow cells are taken from the patient and grown in culture so they are rapidly dividing. Fig. 13.28.

They are reinfected with the genetically engineered retrovirus containing the ada gene. Fig. 13.29.

These immune cells now work and are reintroduced into the blood. Fig. 13.29.

Some SCID children have been able to be removed from their bubbles.

Particle Bombardment: Use of micro-projectiles to insert genes into target animals or plants.

We can add genes to fight disease, not simply add genes to replace defective genes. For example, a gene can be added to kill cancer cells.