BMB844 Exam 2023 PDF

**BMB844 exam 2023** 1. **Precision medicine** Select the wrong statement a. In precision medicine, cancer patients will receive individual treatments based on the presence or absence of specific biomarkers b. Precision medicine treatments are only feasible if the full genotype of the...

**BMB844 exam 2023** 1. **Precision medicine** Select the wrong statement a. In precision medicine, cancer patients will receive individual treatments based on the presence or absence of specific biomarkers b. Precision medicine treatments are only feasible if the full genotype of the patient is known c. Precision medicine treatment can be dependent on the presence of certain non-coding sequence variations in the patient d. A step in a precision medicine treatment can include ex-vivo manipulation of cells from the patient e. Antisense oligonucleotides can be used in some precision medicine treatments 2. **Next Generation Sequencing** a. Exome sequencing of DNA extracted from the cells employing Illumina Next generation b. Sequencing Whole genome sequencing of DNA extracted from the cells employing Illumina c. Next generation Sequencing RNA-seq of mRNA extracted from the cells employing Illumina d. Next generation Sequencing Oxford nanopore sequencing of DNA extracted from the cells e. Oxford nanopore sequencing of mRNA extracted from the cells 3. **CAR-T treatment** a. Combined autologous recombination b. Chimeric antigen receptor c. Cellular antigen recipient d. Cytotoxic antigen receptor e. Chimeric antibody receptor 4. **CAR-T treatment** a. CAR-T therapies are restricted to be used for blood cancer diseases because they are dependent on T-cells b. CAR-T therapies are restricted to be used for blood cancer diseases because they are dependent on B-cells c. In CAR-T therapy a new gene is inserted in patient cells d. In CAR-T therapy a new gene is deleted in patient cells e. CAR-T therapy is dependent on injection of engineered antibodies into patient blood. 5. **CAR-T treatment** a. Combinatorial antigen sensing CAR T cells could aid in precisely targeting T cells to tumors, preventing off-target toxicity b. Tumor-specific antigens are rare compared to tumor-associated antigens (antigens that are expressed on normal tissue but are more highly expressed on tumors) c. SynNotch receptors may expand the targetable tumorantigen space d. SynNotch receptors are problematic because they are also present on normal cells e. When targeting tumor-specific antigen combinations,it may now be possible to use CAR receptorsdirected toward tumor-associated antigens 6. **Cancer** a. ctDNA is an abbreviation for circulating tumor DNA b. In a large proportion of patients ctDNA analysis can give information on clonal evolution and heterogeneity c. Sufficient ctDNA for analysis is only present in a minority of patients d. ctDNA is usually below 250 bp long e. ctDNA is found in the bloodstream and refers to DNA that comes from cancerous cells and tumors 7. **Cancer** a. Exome sequencing of ctDNA can be used to select individualized treatment of breast cancer patients b. ctDNA can be analyzed with ddPCR to identify ESR1 mutations c. CDK4/6 inhibitors significantly prolong progression-free survival (PFS) in combination with endocrine therapy in ER+ breast cancer d. CDK4/6 inhibitors significantly prolong progression-free survival (PFS) in combination with endocrine therapy in ER-breast cancer e. Clonal evolution resulting from treatment with for instance CDK4/6 inhibitors can be analyzed using patient ctDNA as analysis material 8. **NMD-1** a. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that expressionfrom the other allele in the tumor is lost due to epigenetic silencing b. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that expression from the other allele in the tumor is lost due to a de novo genomic deletion in the tumor c. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that expression from the other allele in the tumor is lost due to a de novo splicing mutation that causes exon 18skipping d. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that activity from the other allele in the tumor is lost due to a de novo missense mutation in exon 7 e. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that activity from the other allele in the tumor is lost due to a de novo 3 bp deletion from c.5250 to c.5252 that removes the R1751 codon 9. **NMD-2 (Removed from test-because of typo with exon 14instead of exon 18in two of the possibilities)** a. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that this allele escapes detection due to a SNP located in the primer binding site of one of the PCR primers used to analyze cDNA. b. This can be explained by the fact that the c.5251C\>T mutation is located in exon 14. If the stop mutation had instead been located in exon 24, there would have been no difference between the results form culturing with or without CHX. c. This can be explained by the fact that the c.5251C\>T mutation is located in exon 14. If the stop mutation had instead been located in exon 8 there would have been no difference between the results form culturing with or without CHX. d. If the c.5251C\>T mutation had instead been a missense mutation we would also expect the results from analysis at position c.5251 in tumor biopsy cells cultured with or without CHX to be different from each other (only C at position c.5251from cells cultured without CHX and heterozygosity for c.5251C\>T from cells cultured with CHX). e. A de novo genomic deletion in the tumorhas removed the c.5251C\>T mutation 10. **NMD-2 (Revised after test-Typos corrected)** a. This is consistent with a situation where the c.5251C\>T mutation is inherited and abolishes activity from one BRCA1 allele and that this allele escapes detection due to a SNP located in the primer binding site of one of the PCR primers used to analyze cDNA. b. This can be explained by the fact that the c.5251C\>T mutation is located in exon 18. If the stop mutation had instead been located in exon 24, there would have been no difference between the results form culturing with or without CHX. c. This can be explained by the fact that the c.5251C\>T mutation is located in exon 18. If the stop mutation had instead been located in exon 8 there would have been no difference between the results form culturing with or without CHX d..If the c.5251C\>T mutation had instead been a missense mutation we would also expect the results from analysis at position c.5251 in tumor biopsy cells cultured with or without CHX to be different from each other (only C at position c.5251from cells cultured without CHX and heterozygosity for c.5251C\>T from cells cultured with CHX). e. A de novo genomic deletion in the tumorhas removed the c.5251C\>T mutation 11. **Spinal Muscular Atrophy (SMA)** a. SMA is usually caused by de novo point mutations that disrupt the SMN2 gene b. SMA is usually caused by de novo point mutations that disrupt the SMN1gene c. The majority of patients with SMA have a homozygous deletion of the SMN1 gene d. The majority of patients with SMA have a homozygous deletion of the SMN2 gene e. The majority of patients with SMA inherited alleles with disease-causing point mutations in the SMN1 gene 12. **Spinal Muscular Atrophy (SMA)** a. Patients with SMA can now be treated by employing an antisense oligonucleotide that improves inclusion of SMN2 exon 7 into the mRNA b. Patients with SMA can now be treated by a small molecule drug that improves inclusion of SMN2 exon 7 into the mRNA c. Patients with SMA can now be treated by gene therapy where a functional SMN1 gene is introduced by an AAV vector into motor neuron cells d. Patients with SMA can now be treated by siRNA that removes defective SMN1 in motor neurons e. In the future it is possible that patients with SMA can be treated by stem cell therapy 13. **Small molecule drugs** a. Risdiplam and other similar small molecule drugs like Branaplambinds to the 5\' splice site in SMN2 pre-mRNA and improves inclusion of exon 7 during splicing b. Risdiplam and other similar small molecule drugs like Branaplam binds to the 3\' splice site in SMN2 pre-mRNA and improves inclusion of exon 7 during splicing c. A significant advantage of Risdiplam and other similar small molecule drugs like Branaplam is that they do not need to be injected into spinal fluid or brain to have effect d. Risdiplam increases production of functional SMN protein, but it\'s effect is mediated by binding to RNA e. Risdiplam increases production of functional SMN protein and it\'s effect is not mediated by binding to DNA 14. **Splicing** a. If an exon has two splice sites it will always be included in the mRNA in the splicing process b. A mutation that disrupts a splicing enhancer motif in an exon will always cause complete skipping of that exon in the splicing process c. Splicing inclusion of an exon is dependent on the overall balance between splicing enhancers and splicing silencers and the strength of the splice sites d. Mutations located in introns can not cause exon skipping in the splicing process e. An antisense oligonucleotide that binds to an intron sequence in the pre-mRNA can not increase inclusion of an exon in the splicing process 15. **Unproductive splicing** The figure above shows an example of \"unproductive splicing\" and that this can be decreased, when a splice switching antisense oligonucleotide (SSO) binds to a pseudoexon in intron 14 of the PCCA gene Select the wrong statement a. The figure indicates that enzyme activity in cells from patients with the pseudoexon activating mutation c.1285-1416A\>G can be increased when treated with SSO2 b. Based on the figure it is likely that the c.1285-1416A\>G mutation creates an Exonic Splicing Silencer (ESS), which causes full inclusion of the pseudoexon c. Based on the figure it is likely that the pseudoexon is also included into a large proportion of PCCA mRNA in normal cells d. The figure is consistent with the fact that SSO based inhibition of unproductive splicing can increase activity from some genes e. It is likely that the PCCA pseudoexon harbors several Exonic Splicing Enhancers (ESE) in the region bound by SSO2 16. **Treatment of Huntington disease (HD)** a. Allele-specific targeting of HTT mRNA employing siRNA\'s could be a promising therapeutic approach in HD b. Frequent (high minor allele frequency) neutral SNPs (silent variants) in exons in the HTT gene may be important when developing therapies for HD c. Introduction of a gene therapy viral vector, which can express a normal functioning HTT cDNA in the affected cells could be a promising therapeutic approach in HD d. It is beneficial for specificity and efficiency if many of the nucleotides in therapeutic siRNA\'s consists of modified RNA e. HD is a trinucleotide expansion disease that shows anticipation 17. **Treatment of Parkinson\'s disease(PD)** a. Parkinson\'s disease (PD) can only be caused by mutations in LRRK2 b. Mutations in LRRK2 are not gain of function mutations c. Employing a splice switching oligonucleotide (SSO) to skip a pseudoexon in LRRK2 mRNA may have therapeutic potential d. Employing a splice switching oligonucleotide (SSO) to include a pseudoexon in LRRK2 mRNA may have therapeutic potential e. Splice switching oligonucleotides(SSO) needs to target the splice sites of LRRK2 exon 41 to have therapeutic potentialfor inherited PD 18. **Allele specific QPCR** a. Allele specific primers should differ at the last nucleotide in their 5\'-end b. Allele specific primers typically differ by a mismatch in the middle of their sequence c. Allele specific primers can discriminate because the DNA polymerase will not elongate from a mismatched nucleotide d. Allele specific primers typically can discriminate because there is a difference in melting temperature between perfectly matched primer: template complexes and primer: template complexes with a single mismatch. Discrimination is therefore based on binding or no binding of the different primers depending on mismatch vs no mismatch e. A proofreading DNA polymerase is well suited for allele specific amplification