Nucleic Acid Biochemistry

Nucleic Acid Biochemistry Indian Medical PG Question 1: Which type of RNA contains codons for specific amino acids?

• A. Transfer RNA (tRNA)
• B. Messenger RNA (mRNA) (Correct Answer)
• C. Small nuclear RNA (snRNA)
• D. Ribosomal RNA (rRNA)

Nucleic Acid Biochemistry Explanation: ***Messenger RNA (mRNA)*** - **mRNA** carries the genetic information from **DNA** in the nucleus to the **ribosomes** in the cytoplasm. - This information is encoded in sequences of three nucleotides called **codons**, each specifying a particular amino acid. *Transfer RNA (tRNA)* - **tRNA** molecules are responsible for **carrying specific amino acids** to the ribosome during protein synthesis. - Each **tRNA** has an **anticodon** that base-pairs with a complementary **codon** on the **mRNA** strand. *Small nuclear RNA (snRNA)* - **snRNA** is primarily involved in **RNA splicing**, a process that removes introns from pre-mRNA. - It forms part of the **spliceosome** complex, which is crucial for mature mRNA formation but does not contain codons itself. *Ribosomal RNA (rRNA)* - **rRNA** is a major component of **ribosomes**, the cellular machinery responsible for protein synthesis. - While it plays a critical structural and catalytic role in translation, it does not carry genetic code in the form of codons.

Nucleic Acid Biochemistry Indian Medical PG Question 2: Which diagnostic tool is preferred for metabolic disease screening in children?

• A. Urinalysis
• B. Genetic testing
• C. Complete Blood count
• D. Tandem mass spectrometry (Correct Answer)
• E. Plasma amino acid analysis

Nucleic Acid Biochemistry Explanation: ***Tandem mass spectrometry*** - **Tandem mass spectrometry (TMS)** is the preferred method for newborn screening of many **inborn errors of metabolism** because it can simultaneously detect a wide range of metabolites from a single dried blood spot. - This technique rapidly identifies multiple **amino acid disorders**, **fatty acid oxidation disorders**, and **organic acidemias**, allowing for early intervention. *Urinalysis* - While urinalysis can detect some metabolic abnormalities (e.g., **ketones**, **glucose**), it is not a comprehensive screening tool for the broad spectrum of inherited metabolic diseases. - It primarily identifies end-products of metabolism rather than specific enzyme deficiencies or precursor compounds. *Genetic testing* - **Genetic testing** is highly specific for known genetic mutations, but it is typically used for confirmatory diagnosis or targeted screening when a specific condition is suspected, not for broad, universal newborn metabolic screening. - It can be expensive and time-consuming for population-wide screening of hundreds of potential metabolic disorders. *Complete Blood count* - A **complete blood count (CBC)** assesses cellular components of the blood (e.g., **red blood cells**, **white blood cells**, **platelets**) and is useful for detecting hematological disorders. - It does not directly screen for metabolic diseases, although some metabolic disorders can secondarily affect blood cell counts. *Plasma amino acid analysis* - **Plasma amino acid analysis** can detect specific aminoacidopathies (e.g., **phenylketonuria**, **maple syrup urine disease**), but it is limited to amino acid disorders only. - Unlike tandem mass spectrometry, it cannot simultaneously screen for fatty acid oxidation disorders and organic acidemias, making it less comprehensive for broad metabolic screening.

Nucleic Acid Biochemistry Indian Medical PG Question 3: Which of the following is not a component of a nucleotide?

• A. Sugar
• B. Fatty acid (Correct Answer)
• C. Base
• D. Phosphate

Nucleic Acid Biochemistry Explanation: ***Fatty acid*** - A **fatty acid** is a component of **lipids**, such as triglycerides and phospholipids, which are structurally and functionally distinct from **nucleotides**. - **Nucleotides** are the building blocks of nucleic acids (DNA and RNA), whereas fatty acids are essential for cell membranes and energy storage. *Sugar* - A **pentose sugar** (either **deoxyribose** in DNA or **ribose** in RNA) is a fundamental component of every nucleotide. - This sugar forms the backbone of the nucleic acid strand, covalently linked to the phosphate group and the nitrogenous base. *Phosphate* - A **phosphate group** is a crucial component of a nucleotide, providing the negative charge and forming the phosphodiester bonds that link nucleotides together into a nucleic acid chain. - The number of phosphate groups (mono-, di-, or triphosphate) determines the nucleotide's energy state and function. *Base* - A **nitrogenous base** (adenine, guanine, cytosine, thymine, or uracil) is an essential component of a nucleotide, responsible for genetic information storage and pairing. - This base is attached to the pentose sugar and determines the specific identity of the nucleotide within the DNA or RNA sequence.

Nucleic Acid Biochemistry Indian Medical PG Question 4: Identify the gene commonly involved in the condition shown in the image?

• A. RAS
• B. RET
• C. BRAF V600E (Correct Answer)
• D. P53

Nucleic Acid Biochemistry Explanation: ***BRAF V600E*** - The image displays cells with **Langerhans cell morphology**, including folded nuclei and abundant pale cytoplasm, which are characteristic of **Langerhans cell histiocytosis (LCH)** [1]. - The **BRAF V600E mutation** is the most common genetic alteration found in LCH, present in about 50-60% of cases and activating the MAPK pathway [1]. *RAS* - **RAS mutations** are frequently seen in various cancers, including colorectal adenocarcinoma, pancreatic adenocarcinoma, and non-small cell lung cancer. - While RAS pathway activation can occur in LCH, a direct RAS mutation is not the most common genetic driver; rather, downstream effectors like BRAF V600E are more prominent [1]. *RET* - **RET mutations** are primarily associated with **medullary thyroid carcinoma** (in both sporadic and inherited forms like MEN 2A and MEN 2B) and can also be found in certain types of lung cancer. - They are not a characteristic genetic alteration for Langerhans cell histiocytosis. *P53* - The **TP53 gene** encodes the tumor suppressor protein p53, and mutations in this gene are among the most frequent genetic alterations across a wide spectrum of human cancers. - Although p53 plays a critical role in cell cycle regulation and apoptosis, it is not a primary or common driver mutation specifically associated with Langerhans cell histiocytosis [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 629-630.

Nucleic Acid Biochemistry Indian Medical PG Question 5: Which of the following correctly describes gene therapy ?

• A. Mapping and isolation of gene sequence
• B. Introduction of gene sequence into a cell (Correct Answer)
• C. Synthesis of DNA probes with specific sequence
• D. Use of polymerase chain reaction technique

Nucleic Acid Biochemistry Explanation: ***Introduction of gene sequence into a cell*** - **Gene therapy** fundamentally involves the **delivery of genetic material** (DNA or RNA) into a patient's cells to treat or prevent disease. - The goal is to correct a **genetic defect**, provide a new therapeutic function, or alter gene expression for a desired outcome. *Mapping and isolation of gene sequence* - While essential steps in understanding and preparing for gene therapy, **mapping and isolation** alone do not constitute the therapy itself. - These processes are preliminary research activities to identify the target gene and its location. *Synthesis of DNA probes with specific sequence* - **DNA probes** are short, single-stranded DNA or RNA sequences used to detect the presence of complementary nucleic acid sequences. - Their synthesis is a technique used in **molecular diagnostics** and research, not gene therapy, which aims to introduce functional genes. *Use of polymerase chain reaction technique* - **PCR** is a molecular biology technique used to amplify a specific segment of DNA, creating many copies. - It is a tool for **diagnosis**, research, and sometimes in the preparation of genetic material for therapy, but it is not gene therapy itself.

Nucleic Acid Biochemistry Indian Medical PG Question 6: Subtelomeric rearrangement of genes is frequently associated with intellectual disability. All of the following techniques can be used to diagnose them except:

• A. MALDI (Correct Answer)
• B. FISH
• C. MAPH
• D. cGH array

Nucleic Acid Biochemistry Explanation: ***MALDI*** - **Matrix-assisted laser desorption/ionization (MALDI)** is a soft ionization technique used in mass spectrometry for analyzing biomolecules like proteins and peptides. - It is not suitable for detecting large-scale chromosomal rearrangements such as **subtelomeric deletions or duplications**. *FISH* - **Fluorescence in situ hybridization (FISH)** uses fluorescent DNA probes that bind to specific target regions on chromosomes, allowing for the detection of deletions or duplications [1]. - **Subtelomeric FISH** specifically targets the ends of chromosomes and is a common method for identifying subtelomeric rearrangements [1]. *MAPH* - **Multiplex amplifiable probe hybridization (MAPH)** is a technique used for detecting copy number variations (CNVs), including deletions and duplications, in specific genomic regions. - It can be applied to **subtelomeric regions** by designing probes specific to those areas, making it useful for diagnosing subtelomeric rearrangements. *CGH array* - **Comparative genomic hybridization array (CGH array)** is a high-resolution method that compares the patient's DNA to a control DNA to detect unbalanced chromosomal abnormalities across the entire genome [1]. - It is highly effective in identifying **copy number changes**, including subtelomeric deletions and duplications, associated with intellectual disability [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 187.

Nucleic Acid Biochemistry Indian Medical PG Question 7: Match List-I with List-II and select the correct answer using the code given below the Lists:

• A. A→4 B→1 C→2 D→3 (Correct Answer)
• B. A→3 B→2 C→1 D→4
• C. A→3 B→1 C→2 D→4
• D. A→4 B→2 C→1 D→3

Nucleic Acid Biochemistry Explanation: ***A→4 B→1 C→2 D→3*** - This option correctly matches each carcinoma with its characteristic feature. **Seminoma testis** is **highly radiosensitive** (A→4), making radiation therapy an effective treatment modality with excellent cure rates. **Carcinoma of the prostate** is **hormone-dependent** (B→1), relying on androgens for growth, which is why androgen deprivation therapy is a key treatment [1]. **Basal cell carcinoma** is a locally invasive tumor that **does not significantly spread by lymphatics** (C→2), which contributes to its excellent prognosis despite being the most common skin cancer [2, 4]. **Malignant melanoma** has a prognosis that depends on **Breslow thickness** (D→3), which measures the depth of invasion and is the most important prognostic factor. *A→4 B→2 C→1 D→3* - This option incorrectly states that **carcinoma of the prostate does not spread by lymphatics** (B→2) and that **basal cell carcinoma is hormone-dependent** (C→1). Prostate cancer commonly metastasizes to pelvic lymph nodes via lymphatic spread [1], and BCC is not influenced by hormones. *A→3 B→2 C→1 D→4* - This option incorrectly matches **seminoma testis** with prognosis depending on thickness (A→3) and **malignant melanoma** with being highly radiosensitive (D→4). Seminoma is radiosensitive (not melanoma), and melanoma's prognosis depends on Breslow thickness (not seminoma). *A→3 B→1 C→2 D→4* - This option correctly identifies that **prostate cancer is hormone-dependent** (B→1) and **basal cell carcinoma has limited lymphatic spread** (C→2), but incorrectly associates **seminoma testis** with prognosis depending on thickness (A→3) and **malignant melanoma** with being highly radiosensitive (D→4). These last two matches are reversed. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 993-994. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Skin, pp. 1157-1160. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Disorders Involving Inflammatory And Haemopoietic Cells, pp. 643-644.

Nucleic Acid Biochemistry Indian Medical PG Question 8: Match the following: A) Caplan syndrome- 1) Found first in coal worker B) Asbestosis- 2) Upper lobe predominance C) Mesothelioma- 3) Involves lower lobe D) Sarcoidosis- 4) Pleural effusion is seen

• A. A-3, B-4, C-2, D-1
• B. A-1, B-4, C-3, D-2 (Correct Answer)
• C. A-4, B-2, C-3, D-1
• D. A-2, B-4, C-3, D-1

Nucleic Acid Biochemistry Explanation: **A-1, B-4, C-3, D-2** - **Caplan syndrome** was first described in **coal workers** with **rheumatoid arthritis** and progressive massive fibrosis. - **Asbestosis** is often associated with **pleural effusion**, which can be benign or malignant. - **Mesothelioma** typically involves the **lower lobes** of the lungs, specifically the pleura, and is strongly linked to asbestos exposure. - **Sarcoidosis** is characterized by **non-caseating granulomas**, which have a predilection for the **upper lobes** of the lungs. *A-3, B-4, C-2, D-1* - This option incorrectly states that Caplan syndrome involves the lower lobe; **Caplan syndrome** is defined by the presence of large nodules in the lungs of coal workers with rheumatoid arthritis, and their specific lobar distribution is not a defining characteristic. - This option incorrectly states that Mesothelioma has an upper lobe predominance; **Mesothelioma** is a pleural malignancy and typically involves the **lower lobes**, extending along the pleura. *A-4, B-2, C-3, D-1* - This option incorrectly associates Caplan syndrome with pleural effusion; **Caplan syndrome** manifests as rheumatoid nodules in the lungs, not primarily pleural effusion. - This option incorrectly states that Asbestosis has an upper lobe predominance; **Asbestosis** predominantly affects the **lower lobes** of the lungs, causing interstitial fibrosis. *A-2, B-4, C-3, D-1* - This option incorrectly states that Caplan syndrome has an upper lobe predominance; the defining feature of **Caplan syndrome** is the combination of rheumatoid arthritis and pneumoconiosis, not specific lobar involvement. - This option correctly identifies pleural effusion with asbestosis and lower lobe involvement with mesothelioma, but **Caplan syndrome** is not characterized by upper lobe predominance.

Nucleic Acid Biochemistry Indian Medical PG Question 9: Which of the following separates proteins solely on the basis of their molecular size?

• A. Isoelectric focusing
• B. Chromatography on a diethylaminoethyl (DEAE) cellulose column
• C. Gel filtration chromatography (Correct Answer)
• D. Chromatography on a carboxymethyl (CM) cellulose column

Nucleic Acid Biochemistry Explanation: ***Gel filtration chromatography*** - Also known as **size-exclusion chromatography**, this method separates proteins based on their **hydrodynamic volume** (molecular size and shape). - Larger proteins pass through the column more quickly because they are excluded from the pores of the stationary phase, while smaller proteins enter the pores and have a longer, more tortuous path. *Isoelectric focusing* - This technique separates proteins based on their **isoelectric point (pI)**, which is the pH at which the protein has no net electrical charge. - Proteins migrate through a pH gradient until they reach the point where their net charge is zero. *Chromatography on a diethylaminoethyl (DEAE) cellulose column* - **DEAE cellulose** is an **anion-exchange resin**, meaning it binds **negatively charged** proteins. - Separation is based on the **net charge** of the protein at a given pH. *Chromatography on a carboxymethyl (CM) cellulose column* - **CM cellulose** is a **cation-exchange resin**, meaning it binds **positively charged** proteins. - Separation is based on the **net charge** of the protein at a given pH.

Nucleic Acid Biochemistry Indian Medical PG Question 10: Which of the following methods of protein separation is not dependent on molecular size?

• A. Gel filtration chromatography
• B. SDS-PAGE
• C. Ultracentrifugation
• D. Ion-exchange chromatography (Correct Answer)

Nucleic Acid Biochemistry Explanation: ***Ion-exchange chromatography*** - This method separates proteins based on their **net charge** at a specific pH. - Proteins bind to a charged resin based on their charge, independent of their size. *Gel filtration chromatography* - Separates proteins based on their **molecular size** and shape as they pass through a porous matrix. - **Larger molecules** elute first as they cannot enter the pores, while smaller molecules are retained. *SDS-PAGE* - **Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis** separates proteins primarily based on their **molecular weight**. - SDS denatures proteins and confers a uniform negative charge, allowing migration through a gel matrix based on size. *Ultracentrifugation* - Separates macromolecules and particles based on their **sedimentation rate**, which is influenced by **molecular mass**, density, and shape. - While molecular size is a factor, density and shape also play significant roles in the separation process.

Nucleic Acid Biochemistry Flashcard 1 of 10

Question: _____ are small, noncoding RNA molecules that post-transcriptionally regulate protein expressiontheir 3' UTR contains sequences determining their specificity

Answer: microRNAs

Nucleic Acid Biochemistry Flashcard 2 of 10

Question: Denatured DNA shows hyperchromicity at _____nm

Answer: 260

Nucleic Acid Biochemistry Flashcard 3 of 10

Question: In the first step of alternative splicing, the primary transcript (hnRNA) combines with _____ and other proteins to form the spliceosome

Answer: small nuclear ribonucleoproteins (snRNPS)

Nucleic Acid Biochemistry Flashcard 4 of 10

Question: _____ bases cannot be salvaged to their corresponding nucleotides.

Answer: Pyrimidine

Nucleic Acid Biochemistry Flashcard 5 of 10

Question: The _____ is the site where RNA polymerase II and general transcription factors bind to DNA upstream from a gene locus

Answer: promoter

Nucleic Acid Biochemistry Flashcard 6 of 10

Question: One co-transcriptional modification is the addition of a _____ at the 5' end

Answer: 7-methylguanosine cap

Nucleic Acid Biochemistry Flashcard 7 of 10

Question: Polyadenylation of mRNA protects against degradation by _____

Answer: 3 exonucleases

Nucleic Acid Biochemistry Flashcard 8 of 10

Question: Which base excision repair enzymes are responsible for filling and sealing the gap from the excised bases?_____ (filling) and DNA ligase III (sealing)

Answer: DNA polymerase-

Nucleic Acid Biochemistry Flashcard 9 of 10

Question: Guanosine is converted to _____ via the enzyme purine nucleoside phosphorylase (purine salvage)

Answer: guanine

Nucleic Acid Biochemistry Flashcard 10 of 10

Question: Hypoxanthine is converted to _____ via xanthine oxidase

Answer: xanthine