Genetics Question! Imagine that you are a geneticist at a hospital and you are g

Question

Genetics Question!

Imagine that you are a geneticist at a hospital and you are given a file for a patient whose family has a history of cancer.

The patient, John Doe, is 18 years old and has had a biopsy done on a tumorous growth in his adrenal gland. He has a sister, Jane, and a brother, Bob, who are younger than he is and who are both healthy. His mother, Betty, has a diagnosis of breast cancer. John’s father, Joe, and John’s paternal grandparents have no history of cancer.

Betty is one of four children. Her brother, Tom, and sister, Lucy, have never had cancer or signs of cancer. Both Tom and Lucy are older than Betty. Betty had another brother, Jake, who died very young of leukaemia. Tom has monozygotic twin daughters who are healthy. Betty’s father, Don, died of soft tissue sarcoma in his thirties. Betty’s mother is alive and healthy. Betty’s paternal grandmother, Don’s mother, died of a brain tumor in her thirties. Don had no siblings.

As part of your research, you also consult the OMIM (Online Mendelian Inheritance in Man) database and come up with a short list of candidate genes could mutate to cause John’s tumor.

MULTIPLE ENDOCRINE NEOPLASIA, TYPE I; MEN1

OMIM #13110

• Associated with tumors of the endocrine (hormone producing) glands. Originally known as Wermer syndrome.

• Most common tumors involve parathyroid gland, islet cells of the pancreas, and pituitary gland.

• Other endocrine tumors include adrenal cortical tumors, carcinoid tumors and rare pheochromocytomas, as well as tumors in other parts of the digestive tract.

LYNCH SYNDROME I

OMIM #120435

• Also known as hereditary non-polyposis colorectal cancer (HNPCC).

• Significantly increased risk of developing colorectal cancer.

• Increased risk of developing other types of cancers, such as endometrial (uterine), stomach, breast, ovarian, small bowel (intestinal), pancreatic, prostate, urinary tract, liver, kidney, and bile duct cancers.

LI-FRAUMENI SYNDROME; LFS

OMIM #151623

• Most common types of cancer osteosarcoma (bone cancer), soft-tissue sarcoma, acute leukemia, breast cancer, brain cancer, and adrenal cortical tumors, which is an organ on the top of the kidney.

• Increased risk for melanoma, Wilms' tumor, and cancers of the stomach, colon, pancreas, esophagus, lung, and gonadal germ cells (sex organs) have also been reported.

CARNEY COMPLEX, TYPE 1; CNC1

OMIM #160980

• Associated with spotty skin pigmentation; myxomas, which are benign (noncancerous) connective tissue tumors. Tumors can be benign or cancerous.

• Symptoms develop when a person is in his or her early 20s.

• Other common features are Cushing’s syndrome and multiple thyroid nodules (tumors). Features a combination of weight gain, high blood pressure, diabetes, and easy bruising, caused by the overproduction of the hormone cortisol.

NEUROBLASTOMA, SUSCEPTIBILITY TO

OMIM #256700

• Solid cancerous tumor that begins in the nerve cells outside the brain of infants and young children. It can start in the nerve tissue near the spine in the neck, chest, abdomen, or pelvis, but it most often begins in the adrenal glands.

• Develops most often in infants and children younger than 5.

VON HIPPEL-LINDAU SYNDROME; VHL

OMIM #193300

• Associated with tumors arising in multiple organs. Include hemangioblastomas, spinal cord, and eye.

• Increased risk of developing clear cell renal cell carcinoma, pheochromocytoma, and pancreatic neuroendocrine tumor.

• Other features - kidney cysts, pancreatic cysts, epididymal cystadenomas, and endolymphatic sac tumors.

Later you find out that you have access to a microarray for 10 genes that are associated with John’s type of cancer. The microarray was done comparing normal tissue (control) to cancer samples from six different patients (P1-P6). The results from the microarray are shown below. One of the patients is John.

8. (6) There are three common types of point mutations that can affect the coding sequence of proteins. What are these mutations? How do the mutations change the mRNA sequence and consequently the protein?

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. Andenoviruses are one example that have been used in humans. What is the advantage of using viruses for gene therapy?

11. (2) What are the two main types of gene therapy? How do they differ from each other?

12. (2) What type of gene therapy would your recommend for John and his family? Explain why.

RAS BCLXLCHRB Patient IGF2 P1 P2 P3 TP53 APC DDB1 MRPL48 EGRF1 CTNNB1 P5 P6 Control Red- high expression compared to control Yellow = same expression as control Green low expression compared to control

Explanation / Answer

8)Point mutation also called as small scale mutation effects the normal DNA sequence leading to the mutation of protein sequences .It initiates during the DNA replication at cell cycle stage mitosis and meiosis.

Substitution-It occurs when nomal nucleotide is replaced by different nucleotide resulting in the formation mutation in coding single amino acid.Usualy the mutation happens between A-G or T-C.

Insertion-It occurs when a nucleotide is added to the normal nucleotide resultingin the changes in reading frame of the DNA sequence.It is also regarded as frame shift .

Deletion-A nucleotide is deleted or removed from the DNA sequence causing changes in reading frame of DNA sequences.

Mutation cause alteration in transciption process causing changes in mRNA sequences.While translation mRNA recognise faulty amino acid sequence leading to the formation of mutated polypeptide chain.

9)As per the details given regarding the Joh Doe and his family history, I conclude that the gene reponsible for cancer in the family is X linked.As men inherit one X chromosome from the mother,they are in great risk of the dosorder.Women are usualy carriers or lower in risk of suffering.l,

10)Advantage of using

Adenovirus for gene therapy-

Retrovirus and herpusvirus -Asist in genetic alteration which last long in the cell.

11)Somatic cell gene therapy -The target gene is transfered to somatic cells

Not inhertied to the next generation

Germline gene therapy.-The target gene is transfered to germ cells(eggs and sperm)

Inherited to next generation

12)Somatic cell gene therapy is recommended for the Joe Family.As it is more safe and the cells with cancer can be targeted.With the help of viruses inactive oncogene can be replaced with good gene.

Related Questions

Navigate

• Browse (All)
• Browse G
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.