Question

90170021 201901/P53 pd 8. (3) Lator you find out that you have access to a microarray for 10 gones that are associated with John's type of cancer. The microarray was done comparing normal tissue the microarray are shown below. One of the patients is John sequence of proteins. What are these mutations? How do the mutations change the 9. (2) If you were to suggest gene therapy to the family. how you describe what the main goal of this therapy is? 10. (2) Different virus have been used as vectors for gene therapy Andenovinuses are for gene therapy? 11. (2) What are the two main types of gene therapy? How do they ditfer from each that have been used in humans. What is the advantage of using viruses 12. (2) What type of gene therapy would your recommend for John and his famiy? 0 O Type here to search

Answer 1

Answers:

1. The pedigree chart for the family is as follows:

John as the propositus is indicated by an arrow in the IV generation.

2. The mode of inheritance from the pedigree chart can be observed to be autosomal dominant.

It is autosomal because both males and females are affected. This chart an almost 1:1 ratio of males to females affected. X-linked occurs only when most of the males in the chart are affected.

It is dominant trait because in each generation, one of the parents is affected resulting in offspring being affected. For a trait to be recessive, the parents can be heterozygous carriers and need not be affected by the disease. This means that the trait can skip a generation. As this is not the case in the above chart, the trait is a dominant one.

3. Based on the data from the OMIM database, John is likely to have Li-Fraumeni syndrome.

John has a tumor in his adrenal gland. John's mother has breast cancer and his uncle Jake who died had leukemia. John;s maternal grandfather had soft tissue sarcoma and his great grandmother on the maternal side had brain tumor. Li-Fraumeni syndrome is associated with all these tumors as listed in the OMIM database information. Thus, the mutations in the genes responsible for this syndrome is being passed from generation to generation in this family.

4.  CHEK2 and TP53 are the genes that are associated with the Li-Fraumeni syndrome.

Most of the times families inheriting this syndrome have mutations in the TP53 gene which codes for the p53 tumor suppressor protein. CHEK2 mutations are also found in some cases. This involves defects in the checkpoint kinase 2 protein produced by this gene which is involved in regulation of uncontrolled cell division.

5. There is a chance that John's sister Jane might develop cancer at a later stage. This is because the trait is autosomal dominant. Thus, half of the offsprings are likely to be affected by the allele. Also, there is 50:50 chance of males and females to be affected when one of the parent is affected in this type of inheritance. Thus, Jane is at a risk of developing cancer.

6. Genetic testing is used to confirm mutations associated with a syndrome. In this case, the entire TP53 coding region is sequenced and the presence of mutations including frameshift, missense or nonsense mutations is checked.

For TP53 mutation testing, blood or bone marrow is usually used.