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Indian Institute of Science 2008 Ph.D Biology Banglore entrace - Question Paper

Wednesday, 23 January 2013 12:20Web



INDIAN INSTITUTE OF SCIENCE BANGALORE - 560012

ENTRANCE TEST FOR ADMISSIONS - 2008

Day & Date SUNDAY, 27 APRIL 2008

Time

9.00 A.M. TO 12.00 NOON

1.    This paper consists of 100 multiple choice questions and carrics a total of 100 marks, one mark for each question.


2.    Answers to all questions should be marked only on the OMR sheet provided.

3.    For each question, darken (fill) the appropriate bubble on the OMR sheet to indicate your answer.

4.    Use only IIB pencils to darken the bubbles.

5.    Darken only one bubble per question. If you mark more than one bubble to answer a question, it will be evaluated as incorrect.

6.    If you wish to change your answer, please erase the existing mark completely before filling in the other bubble.

7.    There is no negative marking for wrong answers.

8. Candidates are required to fill in the required fields on the answer sheet attached.

i


1.    A nick in a DNA molecule can be detected by which of the following methods?

(A)    Nested PCR

(B)    Primer extension

(C)    RT-PCR

(D)    Karyotyping

2.    The structure of a double-slranded DNA in a palindromic sequence is

(A)    G-quartets

(B)    Triplex DNA

(C)    Hairpin DNA

(D)    Cruciform DNA

3.    The enzyme responsible for indefinite growth of human cancer cells is

(A)    Telomerase

(B)    DNA polymerase I

(C)    RNA polymerase

(D)    Reverse transcriptase

4.    Spontaneous deamination in a DNA stored at -20C will lead to conversion of cytosine into

(A)    Thymine

(B)    Guanine

(C)    Adenine

(D)    Uracil

5.    Which of the following does NOT apply to triplex DNA

(A)    It is triple-stranded DNA

(B)    Requires only Hoogsteen hydrogen bonding

(C)    Requires Watson-Crickhydrogen bonding

(D)    Forms at neutral or acidic pH

6.    The replicative polymerase in E. coli is

(A)    DNA polymerase I

(B)    DNA polymerase II

(C)    DNA polymerase III

(D)    DNA primase

7.    A DNA chip contains a complete set of random hexanucleotide (6-mers) probes. Out of the 46 = 4096 probes, how many will form perfect complementary duplexes with sequences within the 14 nucleotide single-stranded target DNA, 5' -GAACTGCATTGATA-3*?

(A)    20

(B)    9

(C)    6

(D)    3

8.    A major deviation from Mendel s laws occurs because of

(A)    Linkage

(B)    Mutation

(C)    Reversion

(D)    Complementation

9.    A mixture of 50-mer oligonucleotide and free nucleotides was loaded onro a Sephadex G-50 gel filtration column, which of the following results can be expected?

(A)    The oligonucleotide and the nucleotidcs would be retained in the column and they both can bind the resin

(B)    The oligonucleotide would elute fust

(C)    Nucleotide would elute first

(D)    Both co-elute on this column

10.    Mcthylation of glutamate residues is typically associated with

(A)    Chemotaxis in bacteria

(B)    Nuclear translocation in eukaryotes

(C)    Restriction in bacteria

(D)    inter-cellular transport in plants

11.    Solute movement through which channel is mainly responsible for the resting voltage?

(A)    Porin

(B)    Gap junction

(C)    Glucose

(D)    Potassium

12.    Ribonuclease has four disulfide bonds which were reduced by Dithiothreitol in presence of 8M urea. These reagents were removed by dialysis so thal the protein could refold and the disulfide bonds reformed. If the reformation of S-S bonds occurred randomly, the expected recovery of the biological activity would be

(A)    100%

(B)    80%

(C)    0.95%

(D)    95%

13.    Myoglobin has 153 amino acid residues. If it was a continuous <-helix, the length of myoglobin would be

(A)    36 nm

(B)    53 nm

(C)    55 nm

(D)    23 nm

14.    The Vmax of an enzyme was 90 jrnioles/min/mg of protein. If the molecular mass of the enzyme is 20,000 Da, the turnover number (min *') of the enzyme is

(A)    180

(B)    1800

(C)    90

(D)    18

15.    Which of the following are most likely to be unstable?

(A)    Holocentric chromosomes in C. elegaus

(B)    Melacentric chromosomes in humans

(C)    Dicentric chromosomes in yeast

(D)    Monocentric chromosomes in mice

16.    The peptide bond is not

(A)    apolar

(B)    a partial double bond

(C)    planar

(D)    trans in proteins

17.    The Bohr effect in hemoglobin refers to the

(A)    reduced affinity for O2 at lower pH

(B)    higher pH in actively metabolizing tissues

(C)    increased affinity for O2 at lower pH

(D)    low pH in actively metabolizing tissues

(A)    is found primarily in mucosal secretions

(B)    is one of the less common immunoglobulin types

(C)    has the highest molecular weight of all immunoglobulins

(D)    contains carbohydrate covalently attached to the heavy chain

19.    Which of the following genes is defeciivc in patients suffering from severe combined immunodeficiency syndrome?

(A)    cystic fibrosis transmembrane conductor regulator (CFTR)

(B)    adenosine deaminase

(C)    ribonucleotide reductase

(D)    alpha 2 microglobulin

20.    For which of the following diseases, a recombinant vaccine is available

(A)    Hepatitis A

(B)    Hepatitis C

(C)    Hepatitis B

(D)    Hepatitis E

21.    Which of the following molecules is a poor immunogen in children?

(A)    Bacterial polysaccharides

(B)    Cholera toxoid

(C)    Killed rabies virus

(D)    Live attenuated polio virus

22.    Which of the following proteins is NOT required for the growth of Saccharomyces cerevisiae cells in a medium containing glucose as the sole carbon source?

(A)    Phosphoglyccrate kinase

(B)    GAPDH

(C)    Hexokinase

(D)    Cytochrome C

23.    Incubation of GTP with a protein resulted in the formation of GDP and Pj. The protein is likely to be:

(A)    Ras

(B)    Myc

(C)    Fos

(D)    Myb

24.    FOS, JUN and MYC are:

(A)    proteins expressed on the surface of cancerous cells

(B)    protein kinases that phosphorylate transcription factors regulating expression of cancer genes

(C)    proteins involved in regulation of expression of genes involved in growth promotion

(D)    proteins involved in recombination and DNA repair

25.    Which one of the following staiements i s correct?

(A)    Helper T cells express surface CD8 marker

(B)    Cytotoxic T cells express surface CD4 marker

(C)    Helper T cells express surface immunoglobulin IgG

(D)    Cytotoxic T cells express surface CD8 marker

26.    If secretory IgA protein subjected to SDS-PAGE under reducing conditions, the number of bands one can visualize after staining is:

(A)    1

(B)    2

(C)    3

(D)    4

27.    ATH1 subset of T cells typically secretes

(A)    J5

(B)    IL-13

(C)    IL-4

(D)    IFN-V

28.    Which of the following are examples of primary lyrnphoid organs

(A)    Spleen and lymph node

(B)    Lymph node and Peyer's patches (Q Bone marrow and thymus

(D) Tonsils and liver

29.    Phagocytes kill bacteria using all of the following EXCEPT

(A)    Hydrogen peroxide

(B)    Hydrolytic enzymes

(C)    Low pH

(D)    Sirong reducing agents

30.    Which one of the following sequences in proteins corresponds to N-glycosylalion site? (X indicates any amino acid residue)

(A)    Asn-Ser/Thr

(B)    Asn-X-Ser/Thr

(C)    Asn-X-X-Ser/Thr

(D)    Ser/Thr-Asn

31.    Which of the following secondary metabolites is NOT an anti-cancer drug?

(A)    Paclitaxel

(B)    Podophyllotoxin

(C)    Atropine

(D)    Vincristinc

32.    C3 and C4 plants differ in their photosynthesis, how?

(A)    C4 plants can separate CO2 fixation and Calvin cycle temporally or spatially

(B)    C4 plants can perform the light dependent reactions at night

(C)    C4 plants require less energy for their carbon acquisilion and are, therefore, more efficient

(D)    C3 plants perform the light independent reactions in ihe vascular bundles

33.    If the average molecular weight of one amino acid is 110 Daltons, the molecularweight of a peptide made up of 10 amino acids is expected to be

(A)    1100

(B)    938

(C)    876

(D)    744

34.    A bacterium has 1000 genes. Among the two daughters following replication, there is a probability of 11100 that a gene in either of the daughters has mutated. If a culture of one million cells is raised from one bacterium, the probability that the culture is a true clone (i.e., contains no mutants) is

(A)    about 99 in 100

(B)    about 1 in 100

(C)    about 1 in 10000

(D)    <1X106

iv.    MAPKs

v.    Bad


i. Rho and Rac proteins


d. Apoptotic iactor


e.    activity of


transcription factors


a.

b.    Tumour suppressor gene

c.    GTP-binding proteins


(A)    i-c, ii-a, iii-b, iv-e, v-d

(B)    i-b, ii-a, iii-e, iv-c, v-d

(C)    i-c, ii-d, iii-b, iv-e, v-a

(D)    i-c, ii-b, iii-a, iv-c, v-d

36.    Which of the following is common to the synthesis of all steroid honnones?

(A)    Conversion of testosterone to estradiol

(B)    Cholesterol side chain cleavage

(C)    Isomerization

(D)    Dehydrogenation

37.    Myasthenia Gravis in humans is characterized by increased muscular weakness because of diminishing effects of acetylcholine at neuromuscular junction due to

(A)    Decreased release of acetylcholine at the neuromuscular junction

(B)    Increased activation of acetylcholine receptor

C ) Production of antibodies against acetylcholine receptor

(D) Increased release of inhibitory neurotransmitters at the neuromuscular junction

38.    The posterior pituitary stares and secretes

(A)id FSH

(B)Prolaciin

(C)    ACTHandADH

(D)

(A)    Purines and pyrimidines

(B)    Purines and proteins

(C)    Proteins and lipids

(D)    Pyrimidines and proteins


be labeled in bacterial cells?

(A)    Colcemid

(B)    Adriamycin

(C)    Mimosine

(D)    Hydroxyurea


41.    In which one of the following metabolic reactions is GTP utilized?

(A)    DNA replication

(B)    Fatty acid biosynthesis

(C)    Protein synthesis

(D)    ATP synthesis

42.    Rous Sarcoma virus uses the following enzyme for its replication:

(A)    DNA dependent DNA Polymerase

(B)    RNA dependent RNA Polymerase

(C)    DNA dependent RNA Polymerase

(D)    RNA dependent DNA Polymerase

The protection against Small Pox afforded by prior infection with Cow Pox represents


(A)    Antigenic Specificity

(B)    Antigenic Cross-reactivity

(C)    Viral Super-infection

(D)    Innate Immunity

The antigenic peptides can bind to the T cell receptor when the peptides are only

(A)    in the free form

(B)    when bound by antibody

(C)    when complexed to hapten

(D)    when loaded on to MHC molecules

Which of the following enzymes can be used to radiolabel DNA as well as RNA?

(A)    Klenow fragment of DNA polymerase I

(B)    Polynucleotide kinase

(C)    Reverse transcriptase

(D)    Taq polymerase

46.    Which of the following antibiotics resembles the 3' end of a charged tRNA molecule?

(A)    Puromycin

(B)    Streptomycin

(C)    Tetracycline

(D)    Kananiycin

47.    When heaied, the A26o of DNA sample A increases linearly with temperature, whereas that of DNA sample B increases co-operatively. Which one of the following is correct?

(A)    Both A & B are single stranded

(B)    A is double stranded and B is single stranded

(C)    Both AB are double stranded

(D)    A is single slranded and B is double stranded

48.    Which of the following gases act as signaling moleculcs in eukaryotes?

(A)    Ethylene and Nitrous oxide

(B)    Ethylene and Nitric oxide

(C)    Carbon dioxide and elhylene

(D)    Nitric oxide and oxygen

49.    You dissolve one mole of sodium acetate in 1 L of pure water. The concentration of sodium acetate in this solution is

(A)    .1.0 M

(B)    10.0 M

(C)    <1.0 M

(D)    1.1 M

50.    The secondary structure of a protein can be determined by

(A) NMR spectroscopy,X-ray crystallography and CD speciroscopy

(3) NMR spectroscopy, X-ray crystallography and Fluorescence spectroscopy

(C)    X-ray crystallography, W-visible sp eclroscopy and Fluorcscencc spectroscopy

(D)    CD spectroscopy, Mass spectroscopy and Fluorescence anisotropy

(1)    Northern blot

(2)    Frederick Sanger


(3)    Ramachandran plot

(4)    Southern Blot

(A)    a-2; b-4; c-3; d-1

(B)    a-3; b-1; c-2; d-4

(C)    a-3; b-4;c-2; d-I

(D)    a-2; b-1; c-3; d-4

52. 500 ml of aqueous solution at pH 2 is mixed with 500 ml of aqueous solution at pH 7. Neither solution is buffered; the resulting pH is closest to

(A)    5

(B)    2

(C)    7

(D)    9

53.    The dimension of a subcellularbody is 1.5A. Its dimension in meters is

(A)    1.5 xlG8

(B)    1.5 x 109

(C)    1.5 x 107

(D)    1.5 xlO10

54.    The approximate total number of red blood cells (RBC) in a human body is 25x1012. About 2x1011 RBCs are pmduced per day. Therefore, the RBC on an average survives for

(A)    12.5 days

(B)    2.5 days

(C)    125 days

(D)    200 days

55.    The molecular weight of IgG is 150 kDa. If the mass ratio of antibody: antigen in an IgG-antigen complex is 1:1, the molecular weight of the antigen is

(A)    75 kDa

(B)    150 kDa

(C)    25 kDa CD)    300 kDa

56.    Amino acid composition analysis revealed that a peptide has 2 Ala, 2 Iys and I Phe. Further, a) Ala is observed at the .N-terminus before and after digestion with chymotrypsin and b) a free Lys is reteased after digestion with trypsin. Identify the sequence of the pcplide?

(A)    Ala-Ala-Phe-Lys-Lys

(B)    Ala-Phe-Lys-Ala-Lys

(C)    Ala-Phe-Lys-Lys-Ala

(D)    Ala-Phe-Ala-Lys-Lys

57.    An oligomeric protein dissociates to its component subunits when exposed to temperature below 0C, whereas high salt concentration has little effect on its dissociation. The quaternary structure of the protein is likely to be stabilized by

(A)    van der Waals interaction

(B)    Electrostatic interaction

(C)    Hydrophobic interaction

(D)    Covalent bonds

5 8. S ignal recognili on particle consists o f:

(A)    A single large RNA

(B)    A multi-protein complex

(C)    A complex of a single RNA and multiple proteins

(D)    A complex of multiple RNAs and multiple proteins

59.-    In influenza virus infected cells, 5' cap-dependent translation of host cell mRNAs is severely impaired. The mechanism involves:

(A)    Stealing of 5 cap of the host cell mRNAby the virus

(B)    Cleavage of an essential initiation factor by viral proteases

(C)    Degradation of host cell mRNA by virus induced nucleases

(D)    Competition with the viral mRNA for the initialing ribosome

60.    Two-hybrid analysis is used for:

(A)    Studying DNA-protein interactions

(B)    Studying protein-protein interactions

(C)    Studying regulatory proteins

(D)    Identification of complementary strands of nucleic acids

61.    When the nerve cells send a message for muscle cells to contract, acetylcholine attaches to the receptor on the muscle cell membrane and a channel is opened allowing the Na1 ions to enter the c e 1 through:

(A)    Diffusion

(B)    Osmosis

(C)    Active transport

(D)    Facilitated diffusion

62.    Mitochondria are involved in all of the following, except

(A)    ATP-production

(B)    Apoptosis

(C)    Tricarboxylic acid cycle

(D)    Fatty acid biosynthesis

63.    Pluripotent cells are normally derived fran

(A)    Foetal tissue

(B)    Inner cell mass of blastocyst

(C)    Trophectoderm of blastocyst

(D)    Foetal gonadal ridge

64.    For embryo cloning by nuclear transfer technology, one would require the following to reconstitute an early cleavage-stage embryo:

(A)    Enucleated somatic cell and oocyte nucleus

(B)    Enucleated oocyte and enucleated somatic cell

(C)    Enucleated oocyte and somatic cell nucleus

(D)    Nucleated oocyte and nucleated somatic cell

65.    Which one of the following organisms does not have telomeres?

(A)    Dictyostelium discoideuni

(B)    Tetrahymena Thermophila

(C)    SaccJiaromyces cerevisiae

(D)    Haemophilus influenzae

66.    End product repression differs from feedback inhibition by regulating

(A)    Enzyme activity

(B)    Enzyme synthesis

(C)    Enzyme stability

(D)    Enzyme folding

67.    What is the [S] for the enzyme catalyzed reaction which has an initial velocity of 12.62 mole/liter/min, maximum velocity of 21.85 mole/Iiler/min, and a Kraof 3.88 mole/liler?

(A)    2.51 mole/liter

(B)    5.3 mole/liter

(C)    0.2 mole/liter

(D)    4.31 mole/liter

68.    The following genotypes are found in a populaiion: AA=70, Aa=50 and aa=20. What are the allele frequencies of A and a?

(A)    A=0.68 and a=0.32

(B)    A=Q.63 and a=0.36

(C)    A=0.36 and a=0.63

(D)    AH3.86 and a=0.14

69.    A parental cross invotvi ng pure tall-round seeded and pure dwarf -wrinkle seeded pea plants produced lal 1-round seeded plants. Upon interbreeding the Fi lall-round seeded plants, a total of 400 F2 plants were produced. How many among them were dwarf-round seeded plants?

(A)    25

(B)    50

(D) 250

70.    The concept 'central dogma of molecular genetics' was modi fied by

(A)    Temin and Baltimore

(B)    Benzer

(C)    Crick

(D)    Beadle and Tatum

71.    How many molecules of ATP are consumed a nd produced for two molecules of glucose in glycolysis?

(A)    2 and 2

(B)    2 and 4

(C)    2 and 8

(D)    4 and 8

72.    A 3.2 kb single copy region was amplified by PCR from human genomic DNA. The human genome size is 3.2x109bp. Prior to PCR, what proportion of the DNA consists of the 3.2 kb target sequence?

(A)    10'6

(B)    10*12

(C)    109

(D)    10

73.    A protein rich in which of the following amino acids would have a higher buffering capacity at physiologic pH?

(A)    Aspartic acid

(B)    Arginine

(C)    Serine

(D)    Histidine

74.    To calculate the membrane potential, which of the following equations is used?

(A)    Einstein-Stokes

(B)    Nemst

(C)    Goldman

(D)    Hodgkin-Huxley

75.    The residues that coordinate to the Zn2+ in Zinc finger proteins are

(A)    Asp and Glu

(B)    Cys and Met

(C)    Cys and His

(D)    His and Ser

76.    If the residues are arranged in the descending order of hydrophobicity, which one the following sequences is correct?

(A)    Asp, Ala, Ser, Val, lie

(B)    He, Val, Ala, Scr, Asp

(C)    Asp, He, Ser, Val, Ala

(D)    Val, Ala, lie, Asp, Ser

77.    There are two concentric circles. The radius of the outer one is twicc the radius of the inner circle. What is the ratio of the area between the circles to that of the inner circle?

(A)    1:1

(B)    2:1

(C)    1:3

(D)    3:1

78.    Cellulose is a polymer of

(A)    -Glu-al, 3 Glu-

(B)    -Glu-Bl, 4 Glu-

(C)    -Glu-al, 4 Gal-

(D)    -Glu-Bl, 3 Gal-

79.    Consider the benzene ring in which the C-C bond length is 1.4 A. What is ihe distance in A between diagonally opposite carbon atoms?

(A)    2.8

(B)    1-4

(C)    0.7

(D)    4.2

80.    Which one of the following molecules is a precursor for synthesis of vitamin C in the liver and the kidney of most mammals except higher primates?

(A)    Glucose

(B)    Phenylalanine

(C)    Squalene

(D)    Linolenic acid

81.    The lysosomal sorting signal is

(A)    N-acetyl-glucosamine

(B)    Ran:GTP

(C)    mannose-6-phosphate

(D)    ribose-6-phosphatc

82.    The average density of a soluble protein is 1.33 g/cm3. Calculate the specific volume of a soluble protein, given that the average molecular weight of an amino acid residue is 120 Daltons.

(A)    0.50 mL/g

(B)    0.75 mL/g

(C)    0.33 mL/g

(D)    1.00 mL/g

S3. A guinea pig was given a single injection of 24NaCI. Periodically, blood samples were withdrawn and analyzed immediately for radioactivity. The data are shown below. Calculate ihe biological half-life of MNa in the blood stream

Ti me of injection (hr)

3604

2908

2376

1412

756

329


2

5

10

16

24


84.    Which of the following features of transposons is responsible for genetic polarity?

(A)    The presence of a translation stop signal in ihe transposon

(B)    The inversion of base sequence in iransposon

(C)    The presence of a transcription stop signal in the transposon

(D)    The deletion of base sequence in transposon

85.    The pKa values for adenine (N-l) and guanine (N-7) are 4.2 and 3.2,respectively.

At pH 7, the percentage ofprotonated forms of these groups are:

(A)    0.2 % of adenine and 0.02 % of guanine

(B)    100 % of adenine and 0 % of guanine

(C)    0 % of adenine and 100 % of guanine

(D)    0.02 % of adenine and 0.2 % of guanine

86.    Which of the following amino acids would you expect to find inside of a typical globular protein at pH 7?

(A)    Arg, Lys, Thr, Phe

(B)    Ser, Glu, Asn, Lys

(C)    Val, lie, Phe, Mer

(D)    Ser, Met, Asp, Thr

87.    Which one of the following reagents should be used to selectively inhibit RN A polymerase

II mediated transcription in mammalian cells?

(A)    Alpha-amanitin

(B)    Colchicine

(C)    Puromycin

(D)    Fucomycin

88.    Electrophoresis of a purified protein called X in the presence of sodium dodecyl sulfate and bela-mercaptoethanol shows a single band of 60 kDa. ]h a gel filtraiion experiment, protein X elutes between alcohol dehydrogenase(160 kDa) and pamylase (190 kDa). How many identical subunits protein X is composed of?

(A)    One

(B)    Two

(C)    Five

(D)    Three

89.    When bacteria develop resistance to an antibiotic, the explanation on the basis of natural selection is that

(A)    Resistant bacteria preexisted which were selected by the presence of the antibiotic

(B)    Exposure to the antibiotic induced the resisiance

(C)    The antibiotic is mutagenic

(D)    Resistance is a natural and non-genetic process

90.    Removal of gene activity A from a linear pathway results in higher than normal levels of transcripts from gene B. A reasonable hypothesis would be that

(A)    Gene B must act upstream of gene A

(B)    Gene A has no relation to transcripts of Gene B

(C)    Gene B acts downstream of gene A and is regulated by A directly or indirectly

(D)    The increase in transcript B abundance is an experimental error

91.    The following plant hormone is synthesized from an amino acid precursor

(A)    Ethylene

(B)    Abscisic acid

(C)    Cytokinin

(D)    Auxin

92.    Which enzyme is the target of drugs used to treat disease caused by influenza virus?

(A)    Collagenase

(B)    Hyaluronidase

(C)    Neuraminidase

(D)    Proteinase

93.    Which enzyme complex is responsible for majority of the ATP-dependent degradation of cytosolic proteins?

(A)    26S proteasomes

(B)    Cathepsins

(C)    20S proteasomes

(D)    Calpains

94.    Which family of transcription factors is dircclly activated by Interferons?

(A)    NF-kappa B

(B)    NFAT

(C)    AP-1

(D)    STAT

95.    von Willebrand disease is due to deficiency of a factor involved in

(A)    T cell activation

(B)    Platelet adhesion

(C)    NK cell killing

(D)    Differentiation of B cells

96.    WTiat is the principal characteristic of all oxidizing agents?

(A)    Electron donor

(B)    Removes charge from electrons

(C)    Electron recep tor

(D)    Bums electrons

97.    A cross between two true breeding lines one with dark blue flowers and one with bright white flowers produces FI offspring that are light blue. When the FI progeny are selfed, a 1:2:1 ratio of dark blue to light blue to white flowers is observed. What genetic phenomenon is consistent with these results?

(A)    Epistasis

(B)    Incomplete dominance

(C)    Codominance

(D)    Inbreeding depression

98.    Which of the following compounds would have the highest boiling point?

(A)    CH3CH2CH2CH3

(B)    CH3NH2

(C)    CH3OH

(D)    CH2F2

99.    Which of the following molecules was most likely to have been synthesized in the smooth endoplasmic reticulum?

(A)    Protein

(B)    Phospholipid

(C)    Glucose 0)) Starch

100.    Which of the following is related to affinity maturaiion?

(A)    Class switch recombination

(B)    Homologous recombination

(C)    V(D)J recombination

(D)    Somatic hypermutation

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