1. Genetic Disorders and Gene Therapy
Contemporary Issue – Genetic Disorders and Gene Therapy
Lesson Goals
To understand the nature of genetic diseases.
To differentiate between chromosomal and single gene diseases.
To understand the nature of Down Syndrome and diagnostic methods to detect it.
To understand the important points of heredity including dominant and recessive alleles.
To understand how to predict heredity using a Punnett square.
To understand the nature and heritability of Huntington Disease, Cystic Fibrosis, and Sickle Cell Disease.
To understand the nature of genetic testing and it’s future application to diagnose diseases and the probability of getting genetic diseases.
To understand the nature of gene therapy and it’s future application to cure diseases.
Key Terms;
chromosome chromosomal disease meiosis nondisjunction Down syndrome karyotype amniocentesis autosomal disease gene allele dominant recessive co-dominant widow’s peak genotype phenotype Huntington disease cystic fibrosis sickle cell disease

2. Overview of Lesson Genetic diseases Gene Therapy Chromosomal
Single gene
Gene Therapy
What is it?
How is it done?
Advance Organizer
This lesson will begin with the basics of genetic diseases distinguishing between chromosomal diseases and single gene diseases. Emphasis will be given to patterns of heredity and how to work basic genetic crosses.
The second portion of the lesson will cover genetic testing and discuss how scientists can now identify the presence of genetic diseases using their knowledge of the human genome and proteomics.
The third portion of the lesson will deal with how scientists are learning to treat genetic diseases with gene therapy in which healthy genes are “inserted” into the body of people with genetic diseases.

3. Chromosomal Diseases
Gametes have abnormal chromosome numbers and mutations
Caused by problems with meiosis
Main Idea(s) of This Slide -
There are two types of genetic diseases discussed in this lesson; Chromosomal and Single Gene.
In chromosomal disease, there is an odd number of chromosomes present in the gametes that form the zygote. In normal gametes, there are 23 chromosomes resulting in a zygote with 46 chromosomes after the egg and sperm fuse. For a chromosomal disease to occur, a problem must occur during the meiotic division that forms either the egg or the sperm cell. During meiosis, the chromosomes of a diploid cell (with 46 chromosomes) line up and split to opposite sides of the cell. The resulting gametes from this type of division have only 23 chromosomes. When nondisjunction occurs, two of the chromosomes fail to separate and some of the resulting gametes have one extra copy of a chromosome and others are missing one chromosome entirely. When these gametes are joined with another gamete from the other parent, the resulting zygote has either 45 or 47 chromosomes. This results in developmental abnormalities because the DNA instructions for protein synthesis are flawed.

4. Characteristics of a child with Down Syndrome
-wide, rounded face equal length fingers
-Lower cognitive ability webbed neck
-enlarged tongue
Main Idea(s) of This Slide -
Down Syndrome is a chromosomal disease that results from the presence of an extra chromosome #21. People affected by Down Syndrome have 3 copies of chromosome #21 in each of their cell’s nuclei. Down Syndrome is characterized by a wide, round face, mental retardation, and an enlarged tongue (causing speech difficulty). A karyotype is a visual display of the chromosomes from a cell and can be used to identify if Down Syndrome is present.
Normal female karyotype with 46 chromosomes
Down syndrome karyotype with an extra chromosome 21
Based on: Mader, S., Inquiry Into Life, McGraw-Hill

5. Overview of Lesson Genetic diseases Gene Therapy Chromosomal
Single gene
Gene Therapy
Process
Vectors
Main Idea(s) of This Slide -
In a single gene disease, there is a correct number of chromosomes, but one of the chromosomes contains a gene that is responsible for the disease.

6. Genotype vs Phenotype Genotype refers to the alleles
Phenotype refers to the appearance
Example: Genotype - Phenotype
WW - person has a widow’s peak
Ww - person has a widow’s peak
ww - person has a straight hair line
Main Idea(s) of This Slide -
Genotype is a term that refers to which alleles are found on the chromosomes (WW, Ww, or ww). Phenotype is a term that refers to which expression is seen because of the alleles (widow’s peak or straight hairline).

7. Genetics & Human Diseases
About 4,000 human diseases are thought to be inherited.
Scientists are making good progress figuring out where genes are located on chromosomes.
Genetic diseases are caused by mutations or incorrect sequences, in the normal form of the gene.
Main Idea(s) of This Slide -
Genetic testing involves looking at the genes that code for certain traits. If certain alleles are found that cause diseases, scientists can identify whether a person will have the disease or carry the trait for the disease. There are currently tests for of the diseases that are thought to be inherited. Scientists can identify the “faulty” alleles on the chromosomes very early in development either from cells taken through amniocentesis or by testing cells from embryos intended for implantation through in-vitro fertilization.

8. Huntington’s Disease
Results in a loss of muscle control and mental function.
The symptoms usually do not appear until after 30 years old.
1 in 10,000 people.
Main Idea(s) of This Slide -
Huntington Disease is a neuromuscular genetic disease that is caused by a dominant allele. Huntington Disease is characterized by loss of psychomotor control (usually in adulthood). This particular disease is especially problematic because people do not know they are affected until after they have reached their reproductive years and have quite possibly passed on the trait to their offspring. In this case the alleles will be “H” = Huntington disease and “h” = normal neuromuscular physiology.
Caused by a dominant allele

9. Sickle cell disease (sickle cell anemia)
Can be fatal.
Possible cure: bone-marrow transplants
The sickle cell trait can prevent Malaria

10. Sickle Cell Disease- recessive allele
Red blood cells are sickle shaped, issues with circulation causing anemia and pain
Main Idea(s) of This Slide -
Sickle cell disease is a disease in which the hemoglobin of red blood cells is irregularly shaped causing sickle shaped red blood cells and problems with circulation. The normal allele for proper hemoglobin production is designated (N) for normal. The alternate allele for sickle cell hemoglobin is designated (n) for Sickle. If a person has both alleles that are normal (NN) he will have normally functioning red blood cells and will not have sickle cell disease or sickle cell trait. If the person has both alleles for sickle cell (nn) then he will have sickle cell disease. If the person has one of each allele (Nn), then he will have sickle cell trait but will be phenotypically normal.
Background Information for Teachers
Sickle Cell Trait and Malaria
Having one allele for sickle cell hemoglobin can actually be beneficial to some people.
Malaria is caused by a protozoan parasite called Plasmodium that invades red blood cells and destroys hemoglobin molecules. Plasmodium cannot survive as easily in sickle cell red blood cells and so a person who has sickle cell trait is actually more resistant to this infection than a person who does not have sickle cell trait.
It is interesting to point out to students that sickle cell disease and sickle cell trait is much more common in certain ethnic groups who originate from areas in the world where malaria is a problem (ie. African Americans). In a later lesson malaria will be discussed and it is good to tie that lesson back to this one.
Based on: Harvard Family Health Guide, 1999

11. Hemophilia
A disorder in which a person’s blood does not clot properly.
It is a recessive sex-linked, X-chromosome disorder.
1 in 10,000 males born are afflicted.

12. Overview of Lesson Genetic diseases Gene Therapy Chromosomal
Single gene
Gene Therapy
What is it?
How is it done?
Advanced Organizer
This portion of the lesson will finish up discussing gene therapy. In gene therapy, the genetic disease may be “cured” by inserting a gene with the “healthy” allele.

13. What is Gene Therapy?
Gene therapy is a treatment or cure for disorders caused by mutated genes.
It involves adding a normally functioning copy of the gene(s) to enough affected cells to restore normal function.
Gene therapy is a treatment or cure for diseases caused by defective genes.

14. Gene Therapy Successes
Although no gene therapies have been approved by the FDA for sale, some diseases have been experimentally successful:
Melanoma (skin cancer)
Severe Combined Immunodeficiencies
Hereditary Blindness
Sickle Cell Anemia

16. How is it done? Viral Vector Carrying Healthy Gene
Cell with mutated gene(s)
Vector inserts healthy gene into cell
New gene in the cell along with original genes
Functional proteins are created from the therapeutic gene causing the cell to return to a normal state.

17. Gene Therapy
To design and carry out a gene therapy treatment, a researcher must:
Identify the gene(s) responsible for the disorder.
Make copies of the normal gene.
Insert the copies into vectors.
“Infect” the affected cells with the vectors.
Activate the gene so that transcription and translation take place.

18. Viruses as Vectors Replicate by inserting their DNA into a host cell
Gene therapy can use this to insert genes that encode for a desired protein to create the desired trait
Four different types
Adenovirus
Adeno-Associated Virus (AAV)
Retrovirus
Herpes Simplex Virus (HSV)

20. Research: Building a better Vector
Adenovirus shell delivers genes
HSV-like virus protein tethers DNA to chromosome to keep genes in cell without integration
Instead of giving a drug to fight a disease, you give a cell a healthy or protective gene.
An adenovirus shell is very efficient at delivering DNA to a cell.
An Epstein-Barr virus is very efficient at keeping its DNA inside the cells it infects without causing problems in the infected cells.