Grade: 12 LS Duration: 2.

5 hours
Subject: Biology Number of exercises 4 of 6
Prepared by: Soha Al Adawi Mark: /20
Instagram: Soha.adawi Youtube: Soha.adawii
:‫عزيزي المتعلم‬

.‫ منها فقط‬4 ‫ يجب اختيار‬،‫ تمارين‬6 ‫يتكون هذا االمتحان من‬

ّ

،‫ عليك شطب اإلجابات المتعلقة بالتمرين الذي لم يعد من ضمن اختيارك‬،‫ تمارين‬4 ‫ في حال اإلجابة عن أكثر من‬: ‫تنبيه‬
.‫وإال فسوف يتم تصحيح إجابات األسئلة المرتبطة بالتمارين األربعة االولى على ورقة االجابة‬

.‫ دقيقة لقراءة االمتحان وانتقاء األسئلة‬15 ‫لديك‬

.‫يمكن االستعانة باآللة الحاسبة غير القابلة للبرمجة‬

Exercise 1 (5 pts) Myopathy

The genealogical tree below is that of a family of which some individuals are affected by myopathy.

1- Specify whether the allele responsible for the disease is dominant or recessive.
2- Determine the localization of the gene involved in this disease.
Using molecular biology techniques, DNA analysis can distinguish the normal allele from the mutated allele
causing the disease. Here are the results of analyzes carried out on certain subjects

3- Show that the results of document 2 confirm the localization of the gene determined in part 2.
4- Indicate the genotypes of individuals I-1, I-2 and III-7. Justify your answers.
5- Determine the risk that the couple II-4 and II-5 have:
5.1- a sick girl
5.2- a sick boy.

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Exercise 2 (5 pts) Severity of hemophilia
A fetus is diagnosed with hemophilia A , a genetic disorder caused by a deficiency of clotting factor VIII,
leading to prolonged bleeding. Mutations in the F8 gene, which codes for clotting factor VIII, are the primary
cause of Hemophilia A. These mutations can range from large deletions to small point mutations.
In order to determine the severity of hemophilia in this fetus, the doctor asks for analyzing his DNA. Nonsense
mutation often results in severe forms of hemophilia A. In case of missence mutation, the severity of the disease
depends on the role of the substituted amino acid in the protein’s function.
1- Name two techniques of prenatal diagnosis the doctor can use to detect mutations.
Document 1 shows a partial sequence of the normal and the mutant alleles of the related gene. Document 2 is a
genetic code table.

Non-transcribed 1 27
strand of the Normal ATG GAA GCT TCT TTT GGA AAG GAG CCA
allele
Non-transcribed ATG GAA GCT TCT TTT TGA AAG GAG CCA
strand of the mutant
allele
Document 1
Document 2

2.1- Compare the alleles of document 1.

2.2- Draw out the type of mutation.
3- Determine the amino acid sequence of each of the normal and mutant alleles.
4- Explain how the modification of nucleotides leads to a severe form of hemophilia in this fetus.
The gene related to hemophilia is localized on the non-homologous segment of X and it is known that this
disease affects males only. However, this fetus is born as a girl, who, surprisingly is affected. The karyotype of
this girl shows 45 chromosomes only.

5- Formulate a hypothesis explaining the case of this girl.

To identify the normal and the mutant allele, we incubate the alleles of document 1 in the
presence of a radioactive probe of sequence AAACCT. The autoradiography reveals the
electrophoregram represented in document 3.

6- Justify the following: band A corresponds to the normal allele.

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Exercise 3 (5 pts) Mode of action of lymphocytes
To determine the mechanism leading to the production of antibodies, the following experiments are carried out:
Experiment 1: a mouse is injected with an Ag antigen and the evolution of the plasma level of anti- Ag
antibodies is monitored. The results are shown in document 1.
1- Identify the type of specific immune response.
Experiment 2: Cultures of immune cells taken from the spleen of an S mouse
not immunized against the Ag antigen are produced in the presence of the Ag
antigen. Many days later, we extract the supernatant of each culture and we
measure the level of interleukin 4 and antibody. Document 2 represents the
composition of the cultures and document 3 represents the results obtained.
Cultures
1

Document 2 Document 3

2- Transform document 2 into a table.

3- Indicate the cell at the origin of the secretion of interleukin 4 and antibodies.

4- Show that:

4.1- antibody secretion necessitates the cooperation between t4 lymphocytes, B lymphocytes and macrophages.

4.2- communication between t4 lymphocytes and B lymphocytes takes place through molecules.

A culture comparable to culture 5 of document 2 is performed, but with macrophages whose MHCs have been
degraded. A result similar to that of culture 2 is obtained (document 2 histogram a)

5- Explain these results.

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 Exercise 4 (5 pts) Specific immune responses

We extract a culture of B lymphocytes from the spleen of the mouse S previously immunized with antigen X.
we put this culture in the presence of the antigen X, then, the evolution of the number of BL is followed as a
function of time before and after the addition interleukin 4.
Number of B lymphocytes per ml

Document 1 Document 2

Six days after the addition of interleukin 4, an electron microscope observation of cells taken from this culture
is carried out. This observation reveals the presence of LB and plasma cells. Documents 4 and 5 represent the
results obtained.

1. Interpret the results of document 1.

2. Explain the relationship between the structure of the plasma cell and its function (document 2).

Following the infection of the cells of the mouse by this antigen, we notice the proliferation of new type of
lymphocytes in this mouse (C1) represented in document 3.

3. Identify cell C1.

4. Schematize the recognition between C1 and the

infected cell.

5. Explain how C1 leads to the elimination of the

infected cell.
Document 3

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Exercise 5 (5 pts) Regulation of the sexual cycle.
Document 1 shows the schema of 2 ovarian structures that
are observed in the ovaries of an adult woman during a
period of time between May 1st and May 31st. During the
same period of time, we measure the amount of ovarian
hormones in blood. The results are represented in the same
document.
1- Name structures A and B.
Phases a and b represent phases during the female ovarian
cycle.
2- Specify phase a and phase b.
3- Identify the hormones h1 and h2.
In order to explain the relation between the different organs responsible for the sexual cycle, we perform the
following experiments.
Experiment 1: in a female monkey, the ablation of the pituitary gland interrupts the ovarian and uterine cycles.
Experiment 2: the injection of variable amount FSH and LH to this female and previously subjected to the
ablation of pituitary gland restores the cyclic activity of the ovaries and uterus.
Experiment 3: the injection of variable amount FSH and LH to this female and previously subjected to the
ablation of both pituitary gland and ovaries does not restore the cyclic activity of the uterus..

4- What can you draw out from experiment 1?

5- Indicate one role of each of FSH and LH.
6- Interpret the results of each of experiment 2 and experiment 3.

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Exercise 6 (5pts) Hormonal regulation
In order to study the effect of ovarian hormones on the pituitary gland as well as the uterus, we perform the
following experiments.

Experiment 1: researchers
inject the ovarian hormones
to ovariactomized adult
female mammals and then
they measure the variations
of the levels of LH and
FSH. The conditions and 1
the results are shown in
document 1.

1- Indicate the types

of the feedback
revealed in Document 1
experiment 1. Justify the answer.
2- Name the structures that secrete estrogen during a sexual cycle.

FSH and LH controls the secretion of estrogen and progesterone by the ovaries. Estrogen and progesterone then
controls the cyclic activity of the uterus. To identify the effect of ovarian hormones on the uterus, we carry on the
following experiments (document 2).

A young female rat (before puberty) receives injections as indicated in the following table. We study the
development & proliferation of the endometrium indicated by the variation in the mass of the uterus.

1st lot 2nd lot 3rd lot 4th lot

Injection of 0.1 mℓ of Injection of 0.1 mℓ of
Experimental No injection Injection of 0.1 mℓ of
a solution of a solution of both
conditions (control) a solution of estrogen
progesterone hormones
85 mg (state of uterine
mass of the uterus 15 mg 65 mg 16 mg
lace)
Document 2
3- Interpret the results of document 2.
4- Establish, by referring to what preceded, a functional diagram showing the relations between the
ovaries, the anterior pituitary and the uterus.

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 Answer key

Part Exercise 1: Myopathy (5 pts) Mark

1 The allele responsible for the disease is recessive. The parents I-1 and I-2 are ½
phenotypically normal and have affected child II-3 who must have inherited
the allele responsible for the disease from at least one parent. Therefore the
allele of disease is masked and recessive.

2 Only boys are affected, then the gene is gonosomal. ½

If the gene is localized on the non-homologous segment of Y, boy II-3 who’s
affected must has the genotype XYd, and should inherit Yd from his father I-
1 who should be then affected, but he’s normal so this is not the case.
Therefore, the gene is localized on the non-homologous segment of X.
3 If the genes is localized on the non-homologous segment of Y, the females should 1
have no alleles of this gene. However, the females I-2, II-4 and II-1 show
different copies of the alleles of this gene. Then the gene is not localized on
the non homologous segment of Y.
If the gene is localized on autosomes, or on the homologous segments of X and Y,
then all males and females should show two copies of alleles of this gene.
Males II-3, I-1 and II-5 show all one copy only. So this is not the case.
Therefore, the gene is localized on the non-homologous segment of X and thus the
results confirm part 2.
N
4 I-1: X Y, since he’s a normal male having one X chromosome. His phenotype 1½
reveals his genotype.
I-2: X X : she’s normal having an affected child II-3 who inherit Xd from his
N d

mother.
III-7: XNXd or XNXN: since the normal allele is dominant, it is expressed in
homozygote and heterozygote.
5.1 The girl inherits XN from her father II-5 and since the normal allele is dominant, ½
this girl will be normal whatever gamete she inherits form her heterozygote
mother II-4. Therefore, the risk for the girl of this couple to be affected is
Zero.
5.2 The mother is heterozygous and can give two types of gametes: ½ XN and ½ Xd 1
The father give a gamete with a Y chromosome to get a boy.
The risk to have an affected boy is ½ Xd × 1Y= ½ XdY and therefore the risk to
have an affected boy is ½ .

Part Exercise 2: Severity of hemophilia (5 pts) Mark

1 Chorionic villus biopsy, amniocentesis, sampling of fetal blood ½
2.1 The number of nucleotides in the normal and the mutant alleles is the same 27 ¾
nucleotides.

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 The sequence of nucleotides is the same in both strands except nucleotide 16 where
G in the normal strand is replaced by T in the mutant one.
2.2 Point mutation by substitution ¼
3 Since the given strand is non-transcribed, therefore mRNA is the same as this DNA 1
except we replace T by U.

Normal strand of DNA: ATG GAA GCT TCT TTT GGA AAG GAG CCA
Normal mRNA: AUG GAA GCU UCU UUU GGA AAG GAG CCA
Amino acid sequence of the normal: met- glu - ala- ser – phe -gly – lys – glu- pro

Mutant strand of DNA: ATG GAA GCT TCT TTT TGA AAG GAG CCA
mutant mRNA: AUG GAA GCU UCU UUU UGA AAG GAG CCA
Amino acid sequence of the mutant allele: met- glu - ala- ser – phe

4 The mutation by substitution at the level of the sixteenth the nitrogenous base G is 1
substituted by T in the mutant allele leads to a stop codon in the sequence of
nucleotide in the transcribed m RNA. The translation of this mRNA results
in an incomplete/truncated/ peptide of abnormal 3D structure. Then this is a
nonsense mutation that according to the given often results in severe forms
of hemophilia.
5 Hypothesis: this girl suffers from monosomy X. ½
6 The probe of sequence AAACCT is complementary to TTTGGA, a sequence found 1
between nucleotides 13 and 18 only in the normal allele. Therefore this
radioactive probe hybridizes to the normal allele allowing its visualization
in the electrophoregram.
This sequence TTTGGA is not found in the mutant allele due to mutation, and
therefore this allele won’t hybridize to the probe and won’t be visualized in
the electrophoregram.

Parts Exercise 3: Mode of action of lymphocytes Marks

1 Document one reveals the increase in the amount of anti-Ag antibodies from 0 to 1
10,000 AU four days after the injection of Ag antigen and since antibodies
are the effectors of the humoral specific immune response therefore this
specific immune response is humoral.
2 Cultures 1 2 3 4 5 6 1½
Amount of IL in the supernatent 0 0 0 1500 1,500 1,500
Amount of antibodies in the 0 0 0 0 10,000 10.000
supernatent
This table shows the variation in the amount of IL and antibodies in the supernatant
extracted from the different cultures.
3 interleukin is secreted by the interleukin secreting cells or activated TH ½
antibodies are secreted by the plasmocytes or plasma cells
4.1 the amount of anti-Ag antibodies increases to reach 10,000 AU only in cultures 5 (or ½
6) where the three types of immune cells, macrophages, BL and T4 are
cultured together. While there is no production of anti-Ag antibodies in
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 cultures 1, 2, 3 and 4 where one of these immune cells is absent. This shows
that the secretion of antibodies necessitates the cooperation between T4, B
lymphocytes and macrophages.
4.2 The amount of antibodies increases to reach 10,000 au whether in culture 5 where ½
T4 and BL are cultured together in the same medium or in culture 6 where
T4 and BL are separated by a membrane that allows only molecules to pass
through. This shows that the communication between T4 and we BL takes
place through molecules and not by direct contact.
5 Interleukin is secreted after the differentiation of TH which are proliferated after their 1
activation. The activation of TH takes place upon the double recognition
between this TH and the APC which is the macrophage presenting the non-
self peptide on the surface of MHC. After degradation of MHC, the
macrophage won't be able to present the non-self peptide on its surface and
then TH will not be activated.

Parts Exercise 4: Specific immune responses Marks

1 Before the injection of interleukin 4, the number of BL was low and constant at 1
around 700 BL/ml. After the injection of interleukin 4 at day three, the
number of BL increases to reach 10,000 AU a day 8. This shows that
interleukin 4 stimulates the proliferation BL.
2 Plasma cells show a more developed RER and a larger cytoplasm than BL. These 1
features are characteristics of cells that make protein synthesis. In the case of
plasmocytes, the synthesized protein is the antibody.
3 C1 binds to the virally infected cell as shown in document 3 and then this infected 1
cell is lysed by C1. This indicates that C1 is an activated TC.
4 1

5 The activated Tc or C1 binds to MHC class I carrying the non self peptide on the 1
surface of the infected cell. (double recognition). Then, Tc releases perforin
to form a polyperforin channel in the infected cell and then releases
granzymes in the polyperforin channel. Granzymes are responsible for the
degradation of DNA of the infected cells which is lysed and dead.

Part Exercise 5: Regulation of the sexual cycle mark

1 Structure A: corpus luteum/ yellow body ½
Structure B: Cavitary or graafian follicle
2 Phase a is the luteal phase since the structure found in this phase is the yellow body. ½

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 Phase b is the follicular phase since the structures found in this phase are the
follicles.
3 Since h1 is absent during the follicular phase and shows only one peak during the 1
luteal phase then h1 is the progesterone.
Since h2 is present in both phases, the follicular and luteal phases, and shows two
peaks, where the peak in the follicular phase is greater than that in the luteal phase.
Therefore, h2 is estrogen
4 The pituitary gland controls the ovarian and the uterine cycles. ½
5 FSH: stimulates the growth and maturation of the follicles. ½
LH: Stimulates the development of the luteal body and its peak triggers ovulation.
6 The cyclic activity of ovaries and uterus is restored after the injection of variable 1
amount of FSH and LH . This shows that FSH and LH stimulate the cyclic
activities of the uterus and ovaries.
The cyclic activity of the uterus is not restored in the absence of ovaries and after 1
the injection of FSH and LH, this shows that FSH and LH stimulate the cyclic
activity of the uterus indirectly, through the ovaries.

Part Exercise 6: Hormonal regulation mark

1 Negative feedback: moderate dose of estrogen alone (case A) or the presence of high dose 1 ½
of estrogen coupled with progesterone (case C) decreases respectively the secretion
of FSH and LH from 12 to 3 and from 40 to 10 mg/mL
Positive feedback: High dose of estrogen (case B) increases respectively the secretion of
FSH and LH from 12 to 18 and from 40 to 65 mg/mL.

2 Estrogen is secreted by: granulosa and internal theca during the follicular phase. Luteal ½
cells during the luteal phase
3 In the first and 3rd lot,s when there is no injection or injection of 0.1 ml of a solution of 2
progesterone respectively, the mass of the uterus was almost the same 15 mg, this
indicates that progesterone alone has no influence on the uterus.
However upon injecting 0.1 ml of a solution of estrogen to the 2nd lot, the mass of the
uterus increases from 15 till 65 mg. this means that estrogen stimulates the proliferation
of the uterus and it acts through blood.
But, when 0.1 ml of a solution of both hormones is injected, the uterus mass increases to
85 mg with a state of uterine lace, more than when estrogen was injected alone (65mg
uterus mass) . Therefore, progesterone amplifies the action of estrogen, acts only when
combined with estrogen and is responsible for the formation of uterine lace respectively

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4 a functional diagram showing the relations between the ovaries, the anterior pituitary 1
and the uterus.

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