Genes And Disease/immune System

Front 1

Genes and Disease

Back 1

Genes

Front 2

Asthma is what is known as a complex heritable disease. True/false

Back 2

True. This means that there are a number of genes that contribute toward a persons susceptibility to a disease, and in the case of asthma, chromosomes 5, 6, 11, 14, and 12 have all been implicated.
Chromosome 5 appears to be the most investigated.

Front 3

Why is chromosome 5 the most studied?

Back 3

It is known that this region is rich in genes coding for key molecules in the inflammatory response, seen in asthma, including cytokines, growth factors and growth factor receptors.

Front 4

What are the first signs of Ataxia telangiectasia?They usually appear in the second year of life as a lack of balance and slurred speech.

Back 4

They usually appear in the second year of life as a lack of balance and slurred speech. It is a progressive, degenerative disease characterized by cerebellar degeneration, immunodeficiency, radiosensitivity (X-ray) and a predisposition to cancer.

Front 5

Where has the gene been mapped?

Back 5

On chromosome 11. It was 7 more years before the human ATM gene was cloned.

Front 6

The diverse symptoms seen in A-T reflect the main role of ATM, which is to induce several cellular responses to DNA damage. TRUE/FALSE

Back 6

TRUE. When the ATM gene is mutated, these signaling networks are impaired, and so the cell does not respond to minimize the damage.

Front 7

Is it true that some of the signaling pathways are found in yeast?

Back 7

Yes.Because these pathways appear to be conserved throughout evolution, they are likely to be central to the DNA damage response.
Yeast genetics might very well help advance the knowledge of this disease, which allows more rapid and systematic study of the pathways affected by an ATM mutation.

Front 8

What is Autoimmune polyglandular syndrome type 1(APS1)?

Back 8

It is a rare autosomal recessive disorder that maps to human chromosome 21. A novel gene called AIRE (autoimmune regulator) was identified in 1997. Mutations in this gene are responsible for the pathogenesisi of APS1.

Front 9

Autoimmune disease affecting one organ ultimately results in its destruction in APS. True/False

Back 9

True. Other glands may be affected as well.

Front 10

What is Burkitt's lymphoma?

Back 10

BL is a rare form of cancer predominantly affecting young children in Central Africa, but has been reported elsewhere.

Front 11

Is BL associated with a vrus?

Back 11

yes. The form seen in Africa is associated with the Epstein-Barr virus, although the pathogenic mechanisn is unclear.

Front 12

BL results from chromosome translocations that involve the Myc gene. True/False

Back 12

True.

Front 13

What is a chromosome translocation?

Back 13

This means that a chromosome is broken, which allows it to associate with other parts of chromosomes. The typical one seen in BL, involves chromosome 8, the site of the Myc gene. Myc's expression is changed, thereby disrupting its usual function in controlling cell growth and proliferation.

Front 14

What is Diabetes?

Back 14

It is a chronic metabolic disorder that adversely affects the body's ability to manufacture and use insulin, a hormone necessary for the conversion of food into energy.

Front 15

Why is Diabetes type 1 known as a complex trait/

Back 15

This means that mutations in several genes likely contribute to the disease.

Front 16

Give an example of the last stated answer.

Back 16

It is now known that the IDDM1 locus on chromosome 6 may harbor at least one susceptibility gene for type 1 diabetes. How a mutation at this locus adds to patient risk is not clear. A gene maps to this region of chromosome 6 that also has genes for antigens.

Front 17

In type 1 diabetes , does the body mount an immune assault on its own insulin and the pancreatic cells that manufacture it. True/False

Back 17

True. About 10 loci in the human genome have now been found that seem to confer to susceptibility to type 1 diabetes.

Front 18

What are some of these loci?

Back 18

Among these are: 1.- a gene at the locus IDDM2 on chromosome 11 and 2, the gene for glucokinase(GCK), an enzyme that is key to glucose metabolism which helps modulate insulin secretion, on chromosome 7.

Front 19

What is Di George syndrome?

Back 19

It is a rare congenital(at birth) disease whose symptoms vary greatly between individuals, but commonly include a history of recurrent infection, heart defects and characteristic facial features.

Front 20

What is the cause of DiGeorge syndrome?

Back 20

It is caused by a large deletion from chromosome 22, produced by an error in recombination at meiosis (the process that creates germ cells and ensures genetic variation in offspring).
Several genes from this region are not present in DG syndrome patients.

Front 21

The loss of immune system T cells(produced by the thymus) is a more challenging concern than the oftentimes seen cardiac and speech problems. True/False

Back 21

True.

Front 22

Familial Mediterranean fever occurs most commonly in people of non Ashkenazi Jewish, armenian, Arab and Turkish background. True/False

Back 22

True. FMF is an inherited disorder usually given by recurrent episodes of fever and peritonitis.

Front 23

Where is the gene found in FMF?

Back 23

It is found on chromosome 16. It codes for a protein that is found almost entirely in granulocytes.

Front 24

What does this gene protein normally assist in?

Back 24

This protein is likely to normally assist in keeping inflammation under control by deactivating the immune response. Without this brake, an inappropriate full blown inflammatory reaction occurs.

Front 25

Discovery of the gene mutations will allow for the development of a simple diagnostic blood test for FMF. TRUE/FALSE

Back 25

TRUE. It might be easier to identify environmental triggers that lead to attacks and may lead to new treatments.

Front 26

What is immunodeficiency with hyper-IgM syndrome?

Back 26

HIM is a rare primary immunodeficiency characterized by the production of normal to increased amounts of IgM antibody of questionable quality and an inability to produce sufficient quantities of IgA and IgG.

Front 27

What are individuals with HIM susceptible to?

Back 27

They are susceptible to recurrent infections and are at an increased risk of autoimmune disorders and cancer at a premature age.

Front 28

In a normal immune response to a new antigen, B cells first produce IgM antibody. True/False

Back 28

True. Later however, the B cells switch to produce IgG, IgA, and IgE, antibodies that protect tissues and mucosal surfaces more effectively.

Front 29

What happens in the most common form of HIM?

Back 29

There is a defect in the gene, TNFSF5, found on chromosome X at q26. This gene normally produces a CD40 antigen ligand(CD154), a protein on T cells which binds to the CD40 receptor on B and other immune cells. Without CD154, B cells are unable to receive signals from T cells, and thus fail to switch antibody production to IgA andIgG.

Front 30

The absence of CD40 signals between other immune cells makes individuals with HIM susceptible to infections by opportunistic organisms such as Pneumocystis and Cryptosporidium species. True/False

Back 30

True.

Front 31

Is there a treatment for HIM?

Back 31

Treatment mainly consists of regular IV replacement of the missing IgG antibodies and prompt treatment of infections. Long lasting immunity cannot be acheived without a bone marrow transplant.

Front 32

What is chronic myeloid leukemia?

Back 32

CML is a cancer of blood cells, given by replacement of the bone marrow with malignant, leukemic cells. Many of these cells can be found circulating in the blood and may cause enlargement of the spleen, liver and other organs.

Front 33

How is CML usually diagnosed?

Back 33

It is diagnosed by finding a specific chromosomal abnormality called the Philadelphia(Ph) chromosome, named after the city where it was first found.

Front 34

What is the Ph chromosome a result of?

Back 34

It is a result of atranslocation- or exchange of genetic material, between the long arms of chromosomes 9 and 22. This exchange brings together 2 genes.

Front 35

What 2 genes are brought together?

Back 35

The BCR (breakpoint cluster region) gene on chromosome 22, and the proto-oncogene, ABL(Ableson leukemia virus) on chromosome 9.
The resulting hybrid gene BCR-ABL codes for a fusion protein with tyrosine kinase activity, which activates signal transduction pathways, leading to uncontrolled cell growth.

Front 36

A mouse model has been created that develops a CML like disease when given bone marrow cells infected with a virus containing the BCR-ABL gene. TRUE/FALSE

Back 36

TRUE. In other animal models, the fusion proteins have been shown to transform normal blood precursor cells to malignant cells.

Front 37

What is being done to research the human disease?

Back 37

Antisense oligomers (short DNA segments) that block BCR-ABL were developed that specifically suppressed the formation of leukemic cells while not affecting the normal bone marrow cell development.

Front 38

What id Severe Combined Immunodeficiency(SCID)?

Back 38

SCID is a group of rare, sometimes fatal, congenital disorders characterized by little or no immune response. Sometimes referred to as "bubble boy" disease, is a defect in the specialized white blood cells(B and T lymphocytes). Without these, one is aggressively susceptible to infectious diseases and have a higher than normal risk to certain cancers.

Front 39

Are there any positive treatments available?

Back 39

Though invasive, new treatments such as bone marrow transplants and stem cell transplantation may save as many as 80% of SCID patients.

Front 40

Is SCID an inheritable disease?

Back 40

Yes. All forms are inherited, with as many as half of SCID cases linked to the X chromosome, passed on by the mother.

Front 41

X linked SCID results from what?

Back 41

It results from a mutation in the interleukin 2 receptor gamma(IL2RG) gene which produces the common gamma chain subunit, a component of several IL receptors/

Front 42

What is JAK3?

Back 42

A mutation in JAK3, on chromosome 19, can also result in SCID. Defective IL receptors and IL receptor pathways, prevent the proper development of T lymphocytes that play a key role in identifying invading agents as well as activating and regulating other cells of the immune system.

Front 43

Is there another form of SCID?

Back 43

In the other form of SCID, there is a lack of the enzyme adenosine deaminase(ADA) coded for by a gene on chromosome 20. The substrates for this enzyme accumulate in cells.

Front 44

Immature lymphoid cells of the immune system are particularly sensitive to the toxic effects of these unused substrates, so they fail to reach maturity. TRUE/FALSE

Back 44

TRUE.

Front 45

Nervous system genetic disease.

Back 45

Nervous System.