Genetic Disorders

and
Gene Therapy
Overview of Lesson
• Genetic diseases
– Chromosomal
– Single gene
• Gene Therapy
– What is it?
– How is it done?
Chromosomal Diseases
• Gametes have abnormal
chromosome numbers and
mutations

• Offspring inherit extra

chromosome or are missing a
chromosome

• Caused by problems with

meiosis
Nondisjunction of chromosomes during meiosis

Based on: Brooks/Cole – Thomson Learning

 Characteristics of a child with Down
Syndrome
-wide, rounded face -equal length fingers
-Lower cognitive ability -webbed neck
-enlarged tongue

Normal female Down syndrome

karyotype with 46 karyotype with an extra
chromosomes chromosome 21

Based on: Mader, S., Inquiry Into Life, McGraw-Hill

Overview of Lesson
• Genetic diseases
– Chromosomal
– Single gene
• Gene Therapy
– Process
– Vectors
Important Points about Inheritance

•Genes have different forms, called

alleles

•Each trait is controlled by effects of

two alleles

•Some alleles are:

• dominant/recessive
• other alleles are co-dominant
 Hairline Traits
•Allele for Widow’s Peak •Allele for Straight Hairline
is dominant is recessive
•A person with WW or Ww •A person with ww will have
will have Widow’s Peak a Straight Hairline

http://images.google.com/
 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
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.
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.

Caused by a dominant
allele
 Cystic Fibrosis
Mucus in bronchi is thick,
interfering with lung function

1 in 25 are carriers

One of the first disorders to be

actively studied for gene therapy.

Most lethal autosomal recessive

disorder in U.S.
Sickle Cell Disease- recessive allele
•Red blood cells are sickle shaped, issues with circulation
causing anemia and pain

Based on: Harvard Family Health Guide, 1999

Sickle cell disease
(sickle cell anemia)

• Codominant disorder found in

African Americans.
– 1 in 400 African Americans
• Can be fatal.
• Possible cure: bone-marrow
transplants
• The sickle cell trait can prevent
Malaria
 Hemophilia
• A disorder in which
a person’s blood
does not clot
properly.
• It is a recessive sex-
linked, X-
chromosome
disorder.
“Royalty Disease” • 1 in 10,000 males
born are afflicted.
Adenoside Deaminase (ADA) Deficiency
ADA-deficient persons are affected by
severe immunodeficiency, with recurrent
infections that might be life-threatening.

First disease approved for gene therapy.

Autosomal recessive disorder.

The drug exists but is very

expensive, needs to be injected
in vein for life.
Overview of Lesson
• Genetic diseases
– Chromosomal
– Single gene
• Gene Therapy
– What is it?
– How is it done?
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.
 What is Gene Therapy
• Germline gene therapy would be the
permanent transfer of a gene into
sperm or egg cells.
– Future generations would be “cured”.
• Somatic cell (body cell) gene therapy
is ideally only the transfer of genes
to the affected cells.
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
 How is it done?
Viral Vector Carrying Healthy Gene

Cell with mutated Vector inserts New gene in the

gene(s) healthy gene into cell along with
cell original genes
Functional proteins are created from the therapeutic gene
causing the cell to return to a state.
 Gene Therapy
To design and carry out a gene therapy
treatment, a researcher must:
1. Identify the gene(s) responsible for the
disorder.
2. Make copies of the normal gene.
3. Insert the copies into vectors.
4. “Infect” the affected cells with the vectors.
5. Activate the gene so that transcription and
translation take place.
 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)
Vector Advantages and Disadvantages
• Adenovirus
+ Infects many cell types
− Does not integrate into host genome and can be lost.
• Retrovirus
+ Integrates into host genome and cannot be lost
− Integrates into host genome and can cause cancer
• Adeno-Associated Virus (AAV)
+ Integrates into host genome and cannot be lost
− Difficult to work with.
• Herpes Simplex Virus (HSV)
+ DNA stays in nucleus without integrating into host
genome.
− Only infects cells of the nervous system.
 Gene Therapy
Disappointments
• In 1999 a boy died due to an
immune response to an adenovirus
gene therapy vector.
• Four children have developed
cancer due to a retrovirus gene
therapy vector
My Research: Building a better Vector

Adenovirus
HSV-like virus
shell delivers
protein tethers DNA
genes
to chromosome to
keep genes in cell
without integration