Molecular Biology Answers

5. Familial breast cancer and ovarian cancer (BC) are diagnosed in almost every 10th woman in Europe. Approximately 5-10% of breast cancer is hereditary. Mapped and identified two genes - oncosuppressor –BRCA –1 and BRCA – 2, mutations in which are the cause of familial breast cancer and ovaries. In which human chromosome are the BRCA – 1 and BRCA – 2 genes localized?

    - Complete the quest with:

·               · Online Mendelian Inheritance in Man (OMIM)

·        Human Genome Mutation Database (HGMD)

. Phenylketonuria is one of the most common autosomal recessive diseases caused by a hereditary defect in the PAH gene, which controls the synthesis of the hepatic enzyme phenylalanine hydroxylase. The incidence of diseases in Kazakhstan ranges from 1 in 6,000 to 10,000 newborns. The most common type of mutation is single nucleotide substitutions (missense, nonsense, and splice site mutations). The major mutation in PKU is R408W. Determine the location of the PAH gene and the R408W gene mutation in the human chromosome.

  - Complete the quest with:

• Online Mendelian Inheritance in Man (OMIM)
• Human Genome Mutation Database (HGMD)

3. Cystic fibrosis (cystic fibrosis of the pancreas) is the most common monogenic hereditary disease in the white race. The protein product of the gene, the cystic fibrosis transmembrane regulatory protein, CFTR, is a channel in the apical membranes of epithelial cells, through which chlorine ions are actively transported. According to the literature, the most major (diagnostically significant) mutations in CF patients are the following: delF508, CFTRdel21kb, 2143delT, 3737delA, 2184insA, 394delTT, W1282X, G542X, N1303K. Determine the location of the CFTR gene and the following mutations: delF508, CFTRdel21kb, 2143delT, 3737delA, 2184insA, 394delTT, W1282X, G542X, N1303K in the human chromosome.

    - Complete tasks with:

• Online Mendelian Inheritance in Man (OMIM)
• Human Genome Mutation Database (HGMD)

2. Hemophilia A is a sex-linked disease caused by mutations in the coagulation factor VIII gene. The F8C gene is one of the largest human genes: it contains 26 exons. On which chromosome is the F8C gene located in humans?

   - Complete the quest with:

      • Online Mendelian Inheritance in Man (OMIM)

1. Mutation of the NF1 gene in humans causes a serious genetic disease, type 1 neurofibromatosis (neurofibromatosis, type1). On which chromosome is the NF1 gene located in humans?

   - Complete the quest with:

      • Online Mendelian Inheritance in Man (OMIM)

    A DNA molecule with a length of 5000 base pairs (bp). treated separately with restriction enzymes A and B.

Restrictase A cut DNA into 4 fragments of 2100, 1400, 1000, and 500 bp. Restrictase B gave 3 fragments: 2500, 1300, and 1200 bp.

       Processing of the studied fragment simultaneously with two restriction enzymes gave 6 fragments: 1900, 1000, 800, 600, 500, 200 bp.

      A restriction map of this DNA fragment is presented. Using the restriction data of enzymes A and B, simulate restriction mapping by matching the restriction map of the DNA fragment to this map.    

A patient Marina, 27 years old, was diagnosed with cancer of the right breast with metastases in the lymph nodes (stage II). Marina told the doctor that her sister had osteogenic sarcoma for 17 years, and her brother had acute leukemia at the age of 5 years. Marina's mother died of breast cancer several years ago. Marina's estrogen level is within normal limits. It was taken Marina’s blood for the study of leukocyte DNA.

Questions for discussion:

1. What is the possible cause of tumor development?

2. What type of apoptosis failure leads to breast cancer and other cancers?

3. What type of mutation is the most likely for Marina?

a) mutation of the bcl-2 gene

b) mutation of the bcl-x gene

c) mutation of the p53 gene

d) mutation of the gene encoding the epidermal growth factor receptor

e) mutation of the transforming growth factor gene

4. Find the localization of this gene using the OMIM database.

5. What apoptosis genes are under impact of transcription factor p53?

. A bacterium having a genome size of 3.6 million base pairs would yield a replicon of how many base pairs and why

) When so much damage occurs in DNA that during excision reparation the cell does not have time to completely eliminate them. As a result, after replication of this DNA the daughter chain has “gaps” that are formed at the site of damage of the mother DNA chain,.

1. What type of reparation corrects such damage?

2. What are the molecular mechanisms the cause of this disorder?

Q1-Gene therapy research aims to use genetic material (DNA or RNA) to develop

effective new treatments for a range of serious genetic conditions.

(a)

Critically discuss the strategy you would use to develop a gene therapy

treatment for a named monogenic disorder. Your answer should include

details of the therapeutic genetic material, how you would deliver this to

the affected cells, and the reasons for your choice.

(b)

Evaluate the regulatory challenges and potential safety issues that would

need to be overcome before your new gene therapy treatment could be

used to treat patients.