VOSmed Medical Course

Jakarta – Bandung – Semarang – Jogjakarta - Surabaya

 26
• Apabila seorang ibu memiliki bayi dengan translokasi
kromosom 21, apa yang seharusnya dilakukan sebelum
memperkirakan risiko memiliki anak lain dengan sindroma
Down?
a. Analisis kromosom ibu
b. Analisis kromosom ayah
c. Analisis kromosom baik ayah dan ibunya
d. Pengambilan sampel villi korion
e. Amniosentesis
 Down syndrome
• Down syndrome is by far the most common and best known
chromosomal disorder in humans and the most common cause
of intellectual disability. It is primarily caused by trisomy of
chromosome 21, which gives rise to multiple systemic
complications as part of the syndrome. However, not all
defects occur in each patient; there is a wide range of
phenotypic variation

https://emedicine.medscape.com/article/943216-overview
 Prenatal Screening and Diagnosis
• Prenatal screening using a combination of maternal serum biomarkers and ultrasonography can
detect up to 95% of pregnancies affected by Down syndrome.The false positive rate is 5%. Recently
updated guidelines from the American College of Obstetricians and Gynecologists state the
following: (1) all women should be offered screening for aneuploidy before 20 weeks' gestation and
(2) all pregnant women, regardless of their age, should have the option of diagnostic testing.
• The first prenatal diagnosis of Down syndrome was made in 1968, and screening women with
amniocentesis on the basis of advanced maternal age was gradually introduced into medical practice.
Low maternal serum alpha fetoprotein (MSAFP) levels were associated with Down syndrome in 1983.
Later, elevated human chorionic gonadotropin (hCG) and low unconjugated estriol (uE3) levels were
found to be markers for Down syndrome. More recently, elevated inhibin A levels (in the second
trimester) and reduced pregnancy-associated plasma protein A (PAPP-A) levels (in the first trimester)
have been used to screen for Down syndrome in pregnancy. Maternal serum biomarkers can also be
used to detect nonstandard trisomy 21 (translocations and mosaicism); however, detection rates for
low-level mosaicism may be low.
• A substantial proportion of pregnancies are terminated after a prenatal diagnosis of Down syndrome.
First-trimester screening
• For pregnant women, for whom an early diagnosis is important, a first-trimester "combined test" performed at
11-14 weeks involving sonographic testing for NT together with testing for PAPP-A and hCG provides a detection
rate of 82-87% for Down syndrome.
Second-trimester screening
• Tests used for second-trimester screening include the triple and quadruple screens. The triple screen measures
serum hCG, AFP and unconjugated estriol to calculate the risk of Down syndrome and can detect up to 69% of
Down syndrome pregnancies. Currently, the quadruple test, usually performed at 15-18 weeks' gestation, is the
most common screening test performed in the second trimester. This screen measures inhibin A in addition to
the biochemical markers measured in the triple screen and provides an 81% detection rate for Down syndrome.
In addition, the quadruple test serves as a screening test for open neural tube defects (since it involves
measurement of AFP) and can also detect trisomy 18.
Integrated screening
• With integrated screening, the pregnant woman undergoes a first-trimester screening (involving NT testing,
PAPP-A, hCG) followed by the quadruple screen in the second trimester. This combined screening approach
increases the detection rate of Down syndrome to 95%, with a false positive rate of only 5%.
Invasive diagnostic tests
• Amniocentesis, routinely performed at 14-16 weeks’ gestation, remains the criterion standard of invasive
diagnostic tests. Testing for chromosomal disorders is 99.5% accurate. Rare cases of mosaicism are missed, and
results can be inaccurate if maternal-cell contamination occurs. The procedure is associated with a small risk of
pregnancy loss (1:200-300).
• Chorionic villus sampling (CVS) is performed at 10-13 weeks’ gestation; earlier testing is thought to be
associated with a 1 in 300-1000 risk of fetal transverse limb deficiency, a small risk of maternal cell
contamination, and a 0.5-1% risk of a fetal loss after the procedure. The accuracy of CVS (96-98%) is less than
that of midtrimester amniocentesis, because of confined placental mosaicism and maternal-cell contamination.
• Percutaneous umbilical blood sampling (PUBS) is approximately 95% successful in obtaining a blood sample for
cytogenetic testing. The pregnancy-loss rate is 3.25% for PUBS done for chromosomal indications, compared
with 1.25% and 2.75% for PUBS done for nonchromosomal indications. The indication for the procedure greatly
increases the risk of procedure-related pregnancy loss.
• The availability of in vitro fertilization has allowed preimplantation diagnosis of single-gene disorders, sex
selection for X-linked disorders, and identification of chromosomal aneuploidies. After a biopsy sample is
obtained from the first polar body, the blastocyst, or the 6-cell to 8-cell embryo, FISH can then be used to
diagnose fetal aneuploidy. However, standard cytogenetic confirmation is not possible for the preimplantation
diagnosis.
 Analisa
• Apabila seorang ibu memiliki bayi dengan translokasi
kromosom 21, apa yang seharusnya dilakukan sebelum
memperkirakan risiko memiliki anak lain dengan sindroma
Down?
a. Analisis kromosom ibu
b. Analisis kromosom ayah
c. Analisis kromosom baik ayah dan ibunya
d. Pengambilan sampel villi korion
e. Amniosentesis
 27
• Suatu jaringan mengandung sedikit bahan dasar amorf,
sejumlah sel dengan inti lonjong, dan banyak serat. Pada
pewarnaan hematoksilin eosin seratnya tampak seperti pita
atau lembaran berwarna merah muda yang tersusun teratur
dan padat. Apakah nama jaringan tersebut?
a. Epitel selapis kolumnar
b. Epitel selapis kuboid
c. Jaringan ikat longgar
d. Jaringan ikat padat kolagen
e. Peritoneum
 Connective tissue
• Connective tissue consists of three main components: cells, protein fibers, and an
amorphous ground substance. Together the fibers and ground substance make up the
extracellular matrix. Whereas the other tissue types (epithelium, muscle, and nervous
tissue) are largely made up of cells, the extracellular matrix is the major component of most
connective tissue.
Connective Tissue Fibers
• The three types of connective tissue fibers are:
• Collagen fibers - most are type I collagen (most abundant protein in the body)
– Tensile strength - resistance to stretching
• Elastic fibers - contain elastin and fibrillin
– Elasticity - can be stretched, yet still, return to its original length
• Reticular fibers - contain type III collagen
– Support - network of thin fibers

http://www.histologyguide.com/slidebox/03-connective-tissue.html
• Connective tissue is classified based on the characteristics of its cellular
and extracellular components. The main criteria are the type of cells,
arrangement and type of fibers, and composition of the extracellular
matrix.
• Loose (areolar) connective tissue has a sparse, irregular network of
collagen and elastic fibers suspended within a relatively large amount
of ground substance.
• Dense regular connective tissue is composed of type I collagen fibers
oriented in the same direction. It provides tensile strength in one
direction.
• Dense irregular connective tissue contains type I collagen fibers woven
in multiple directions. It provides tensile strength in multiple directions.
 Analisa
• Suatu jaringan mengandung sedikit bahan dasar amorf,
sejumlah sel dengan inti lonjong, dan banyak serat. Pada
pewarnaan hematoksilin eosin seratnya tampak seperti pita
atau lembaran berwarna merah muda yang tersusun teratur
dan padat. Apakah nama jaringan tersebut?
a. Epitel selapis kolumnar
b. Epitel selapis kuboid
c. Jaringan ikat longgar
d. Jaringan ikat padat kolagen
e. Peritoneum
 28
• Pengiriman sinyal sering memerlukan suatu tanggapan cepat
dan terminasi cepat terhadap sinyal. Hal ini dapat dicapai
dengan cara apa?
a. Degradasi sinyal atau caraka kedua
b. Aktivasi protein G
c. Aktivasi enzim kinase
d. Aktivasi adenilat siklase
e. Aktivasi enzim fosforilasi
 Binding Initiates a Signaling Pathway
• Cell-surface receptors, also known as transmembrane receptors, are membrane-
anchored (integral) proteins that bind to external ligand molecules. This type of
receptor spans the plasma membrane and performs signal transduction in which
an extracellular signal is converted into an intracellular signal. Ligands that
interact with cell-surface receptors do not have to enter the cell that they affect.
Cell-surface receptors are also called cell-specific proteins or markers because
they are specific to individual cell types. Each cell-surface receptor has three
main components: an external ligand-binding domain, a hydrophobic
membrane-spanning region, and an intracellular domain inside the cell. The
ligand-binding domain is also called the extracellular domain. The size and extent
of each of these domains vary widely, depending on the type of receptor. Cell-
surface receptors are involved in most of the signaling in multicellular organisms.

https://courses.lumenlearning.com/boundless-biology/chapter/propagation-of-the-cellular-signal/
• There are three general categories of cell-surface receptors: ion channel-linked receptors, G-
protein-linked receptors, and enzyme-linked receptors.
– Ion channel-linked receptors bind a ligand and open a channel through the membrane that
allows specific ions to pass through. To form a channel, this type of cell-surface receptor has an
extensive membrane-spanning region. When a ligand binds to the extracellular region of the
channel, there is a conformational change in the protein’s structure that allows ions such as
sodium, calcium, magnesium, and hydrogen to pass through.
– G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The
activated G-protein then interacts with either an ion channel or an enzyme in the membrane. All
G-protein-linked receptors have seven transmembrane domains, but each receptor has its own
specific extracellular domain and G-protein-binding site.
– Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated
with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme.
Other enzyme-linked receptors have a small intracellular domain that interacts directly with an
enzyme. When a ligand binds to the extracellular domain, a signal is transferred through the
membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the
cell that eventually leads to a response.
• After the ligand binds to the cell-surface receptor, the
activation of the receptor’s intracellular components sets off a
chain of events that is called a signaling pathway or a signaling
cascade. In a signaling pathway, second messengers, enzymes,
and activated proteins interact with specific proteins, which
are in turn activated in a chain reaction that eventually leads to
a change in the cell’s environment. The events in the cascade
occur in a series, much like a current flows in a river.
Interactions that occur before a certain point are defined as
upstream events; events after that point are called
 Analisa
• Pengiriman sinyal sering memerlukan suatu tanggapan cepat
dan terminasi cepat terhadap sinyal. Hal ini dapat dicapai
dengan cara apa?
a. Degradasi sinyal atau caraka kedua
b. Aktivasi protein G
c. Aktivasi enzim kinase
d. Aktivasi adenilat siklase
e. Aktivasi enzim fosforilasi
 29
• Manakah yang merupakan contoh dari penurunan epistasis
resesif ganda pada manusia?
– Achondroplasia dwarfism
– Haemofilia
– Bisu-tuli
– Hipertrichosis
– Albinisme
 Epistasis
• Mendel’s studies in pea plants implied that the sum of an individual’s phenotype was controlled by genes (or as he called them, unit
factors), such that every characteristic was distinctly and completely controlled by a single gene. In fact, single observable
characteristics are almost always under the influence of multiple genes (each with two or more alleles) acting in unison. For example,
at least eight genes contribute to eye color in humans.
• In some cases, several genes can contribute to aspects of a common phenotype without their gene products ever directly interacting.
In the case of organ development, for instance, genes may be expressed sequentially, with each gene adding to the complexity and
specificity of the organ. Genes may function in complementary or synergistic fashions, such that two or more genes need to be
expressed simultaneously to affect a phenotype. Genes may also oppose each other, with one gene modifying the expression of
another.
• In epistasis, the interaction between genes is antagonistic, such that one gene masks or interferes with the expression of another.
“Epistasis” is a word composed of Greek roots that mean “standing upon.” The alleles that are being masked or silenced are said to be
hypostatic to the epistatic alleles that are doing the masking. Often the biochemical basis of epistasis is a gene pathway in which the
expression of one gene is dependent on the function of a gene that precedes or follows it in the pathway.
• An example of epistasis is pigmentation in mice. The wild-type coat color, agouti (AA), is dominant to solid-colored fur (aa). However, a
separate gene (C) is necessary for pigment production. A mouse with a recessive c allele at this locus is unable to produce pigment and
is albino regardless of the allele present at locus A (Figure 1). Therefore, the genotypes AAcc, Aacc, and aacc all produce the same
albino phenotype. A cross between heterozygotes for both genes (AaCc x AaCc) would generate offspring with a phenotypic ratio of 9
agouti:3 solid color:4 albino. In this case, the C gene is epistatic to the A gene.

https://courses.lumenlearning.com/wm-biology1/chapter/reading-epistasis-2/
 • Hearing loss is the most common sensory disorder, and at least 50% of cases are due to a genetic
etiology. Two-thirds of individuals with congenital deafness are nonsyndromic. Among the
nonsyndromic forms, the large majority are monogenic autosomal recessive traits. The current work
summarizes mutations in the GJB2, SLC26A4, 12SrRNA, and GJB3 and their prevalence in 318
students with autosomal recessive nonsyndromic hearing loss at schools for the deaf or special
needs schools in 9 cities in Hebei Province, China. Deafness gene mutations were identified in 137
students via a gene chip, time-of-flight mass spectrometry, fluorescence quantitative PCR, and gene
sequencing.
• Mutations were detected at a rate of 43.08%. A homozygous mutation of the GJB2 gene was found in
16 students (5.03%), a heterozygous mutation of that gene was found in 38 (11.95%), a homozygous
mutation of the SLC26A4 gene was found in 22 (6.92%), a heterozygous mutation of that gene was
found in 59 (18.55%), and a heterozygous mutation of the mitochondrial 12SrRNA gene was found in
2 (0.63%). In addition, there were 15 families in which a student's parents had normal hearing.
Compound heterozygous mutations of the GJB2 gene were found in 3 families (20%) and mutations
of the SLC26A4 gene were found in 9 (60%). Thus, this study has provided a molecular diagnostic
basis for the causes of deafness, and this study has also provided a scientific basis for the early
prevention of and intervention in deafness.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561242/
 Analisa
• Manakah yang merupakan contoh dari penurunan epistasis
resesif ganda pada manusia?
– Achondroplasia dwarfism
– Haemofilia
– Bisu-tuli
– Hipertrichosis
– Albinisme
 30
• Apabila seorang ibu memiliki bayi dengan kromosom mozaik
21, berapa persenkah risiko ibu tersebut memiliki anak lainnya
dengan sindroma Down?
a. 12% jika ibu merupakan carrier seimbang
b. 3% jika ayahnya merupakan carrier seimbang
c. 25%
d. 50%
e. Tergantung pada usia maternal
 Down syndrome
• Down syndrome is by far the most common and best known
chromosomal disorder in humans and the most common cause
of intellectual disability. It is primarily caused by trisomy of
chromosome 21, which gives rise to multiple systemic
complications as part of the syndrome. However, not all
defects occur in each patient; there is a wide range of
phenotypic variation

https://emedicine.medscape.com/article/943216-overview
• Down syndrome is caused by the following 3 cytogenic variants:
– Three full copies of chromosome 21
– Chromosomal translocation that results in 3 copies of the critical region for Down syndrome
– Mosaicism
• In 94% of patients with Down syndrome, full trisomy 21 is the cause; mosaicism (2.4%) and
translocations (3.3%) account for the remaining cases. Approximately 75% of the unbalanced
translocations are de novo, and approximately 25% result from familial translocation.
• A free trisomy 21 results from nondisjunction during meiosis in one of the parents. This occurrence is
correlated with advanced maternal and paternal age. About 95% of the time, the error is maternal
nondisjunction, with meiosis I errors occurring three times as frequently as meiosis II errors. The
remaining 5% cases are paternal in origin, and meiosis II errors predominate.
• Advanced maternal age remains the only well-documented risk factor for maternal meiotic
nondisjunction. However, understanding of the basic mechanism behind the maternal age effect is
lacking.
• Translocation occurs when genetic material from chromosome 21 becomes attached to
another chromosome, resulting in 46 chromosomes, with 1 chromosome having extra
material from chromosome 21 attached. It may occur de novo or be transmitted by one of
the parents. Translocations are usually of the centric fusion type. They frequently involve
chromosome 14 (14/21 translocation), chromosome 21 (21/21 translocation), or
chromosome 22 (22/21 translocation).
• Mosaicism is considered a postzygotic event (ie, one that occurs after fertilization). Most
cases result from a trisomic zygote with mitotic loss of one chromosome. As a result, two
cell lines are found: one with a free trisomy and the other with a normal karyotype. This
finding leads to great phenotypic variability, ranging from near normal to the classic trisomy
21 phenotype.
• Cytogenetic and molecular studies suggest that dup21(q22.1-22.2) is sufficient to cause
Down syndrome. The DSCR contains genes that code for enzymes, such as superoxide
dismutase 1 (SOD1), cystathionine beta-synthase (CBS), glycinamide ribonucleotide
synthase-aminoimidazole ribonucleotide synthase-glycinamide formyl transferase (GARS-
AIRS-GART).
 Analisa
• Apabila seorang ibu memiliki bayi dengan kromosom mozaik
21, berapa persenkah risiko ibu tersebut memiliki anak lainnya
dengan sindroma Down?
a. 12% jika ibu merupakan carrier seimbang
b. 3% jika ayahnya merupakan carrier seimbang
c. 25%
d. 50%
e. Tergantung pada usia maternal
 31
• Coarse facies dan organomegali merupakan petanda penting
dari kelainan organel yang mana?
a. Lisosom
b. Peroksisom
c. Mitokondria
d. Retikulum endoplasma
e. Komplek Golgi
 Lysosomal Storage Disorders
• Lysosomal storage disorders are rare inborn errors of
metabolism, with a combined incidence of 1 in 1500 to 7000
live births. These relatively rare disorders are seldom
considered when evaluating a sick newborn. A significant
number of the >50 different lysosomal storage disorders,
however, do manifest in the neonatal period and should be
part of the differential diagnosis of several perinatal
phenotypes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768319/#!po=18.7500
• Several of the LSDs have classic dysmorphic
features that can be identified in the newborn.
MPS VII, the deficiency of β-glucuronidase, has
a spectrum of clinical findings. A review of the
literature reveals that some patients present as
early as at birth, and have severe involvement,
including a characteristic appearance of coarse
facies with a depressed nasal bridge and widely
spaced eyes. den Hollander also described a
patient with MPS VII that presented with an
enlarged nuchal translucency in early
pregnancy.
• Congenital ascites results from a wide range of etiologies including abnormalities
of the genitourinary tract or gastrointestinal tract or cardiovascular anomalies, or
it can arise secondary to a hematologic disorder. In recent years there has been
increased awareness that ascites in the neonate may be a manifestation of 1 of
several different LSDs. The event that triggers the accumulation of excessive fluid
within the peritoneal cavity in infants with LSDs is a source of considerable
controversy in the literature. The mechanism contributing to the development of
hydrops in storage diseases may involve the obstruction of venous blood return
resulting from organomegaly. Anemia, caused by either hypersplenism or the
reduction of erythropoietic bone marrow stem cells caused by infiltrating storage
cells, may be a trigger. Hydrops can also result from hypoproteinemia caused by
liver dysfunction. Other conditions that may trigger ascites in metabolic disease
are congestive heart failure and liver cirrhosis.
 Analisa
• Coarse facies dan organomegali merupakan petanda penting
dari kelainan organel yang mana?
a. Lisosom
b. Peroksisom
c. Mitokondria
d. Retikulum endoplasma
e. Komplek Golgi
 32
• Pernyataan manakah yang berhubungan dengan penurunan
DNA mitokondria?
a. Sifat diturunkan menurut garis maternal
b. Ayah ikut berkontribusi pada penurunan sifat
c. Kemungkinan untuk menderita suatu kelainan 50%
d. Kelainan atau mutasi DNA mitokondria selalu diturunkan kepada
generasi berikutnya
e. Bila terjadi kelainan pada anak maka dipastikan bahwa kelainan
tersebut di turunkan dari ibunya
 Mitochondrial DNA
• Mitochondria are structures within cells that convert the energy from food into a form that
cells can use. Each cell contains hundreds to thousands of mitochondria, which are located
in the fluid that surrounds the nucleus (the cytoplasm). Although most DNA is packaged in
chromosomes within the nucleus, mitochondria also have a small amount of their own DNA.
This genetic material is known as mitochondrial DNA or mtDNA. In humans, mitochondrial
DNA spans about 16,500 DNA building blocks (base pairs), representing a small fraction of
the total DNA in cells.
• Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial
function. Thirteen of these genes provide instructions for making enzymes involved in
oxidative phosphorylation. Oxidative phosphorylation is a process that uses oxygen and
simple sugars to create adenosine triphosphate (ATP), the cell's main energy source. The
remaining genes provide instructions for making molecules called transfer RNA (tRNA) and
ribosomal RNA (rRNA), which are chemical cousins of DNA. These types of RNA help
assemble protein building blocks (amino acids) into functioning proteins.

http://ghr.nlm.nih.gov/mitochondrial-dna#idiograms
 • Mitochondrial DNA is inherited maternally in most animals.
• There are diverse mechanisms to eliminate paternal
mitochondria or their DNA in zygotes.
• Paternal mitochondria are degraded by autophagy in C.
elegans or the ubiquitin–mediated mechanism in mammals.
• Paternal mtDNA is degraded by specific nucleases in some
species.
• Paternal mitochondria and/or their mtDNA are physically
excluded prior or on fertilization in some species.
https://www.sciencedirect.com/science/article/pii/S0167488913001092
 Analisa
• Pernyataan manakah yang berhubungan dengan penurunan
DNA mitokondria?
a. Sifat diturunkan menurut garis maternal
b. Ayah ikut berkontribusi pada penurunan sifat
c. Kemungkinan untuk menderita suatu kelainan 50%
d. Kelainan atau mutasi DNA mitokondria selalu diturunkan kepada
generasi berikutnya
e. Bila terjadi kelainan pada anak maka dipastikan bahwa kelainan
tersebut di turunkan dari ibunya
 33
• Seorang remaja lelaki berusia 17 tahun dibawa ke dokter
dengan keluhan berat badan meningkat (85 kg). Ia juga
mengalami gangguan tinggi tubuh (145 cm). Manakah
pernyataan yang benar mengenai kasus ini ?
a. Faktor yang berperan sebagai kontributor sudah diketahui
b. Kondisi ini disebabkan oleh mutasi satu gen (single gene mutation)
c. Kondisi ini merupakan kombinasi dari poligenik dan faktor
lingkungan
d. Pola penurunan belum diketahui
e. Tidak pernah ditemukan sebagai mutasi de novo
 Analisa
• Seorang remaja lelaki berusia 17 tahun dibawa ke dokter
dengan keluhan berat badan meningkat (85 kg). Ia juga
mengalami gangguan tinggi tubuh (145 cm).
• BMI: 40.2 kg/m2  obesitas
 obesity
• Obesity is a complex, heritable trait influenced by the interplay
of genetics, epigenetics, metagenomics and the environment.
With the increasing access to high precision diagnostic tools for
genetic investigations, numerous genes influencing the
phenotype have been identified, especially in early onset
severe obesity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226269/
• Genetic causes of obesity can be broadly classified into:
– Monogenic causes: those caused by a single gene mutation, primarily
located in the leptin- melanocortin pathway.
– Syndromic obesity: severe obesity associated with other phenotypes
such as neurodevelopmental abnormalities, and other organ/system
malformations.
– Polygenic obesity: caused by cumulative contribution of a large
number of genes whose effect is amplified in a ‘weight gain
promoting’ environment.
 analisa
• Manakah pernyataan yang benar mengenai kasus ini ?
a. Faktor yang berperan sebagai kontributor sudah diketahui
b. Kondisi ini disebabkan oleh mutasi satu gen (single gene mutation)
c. Kondisi ini merupakan kombinasi dari poligenik dan faktor
lingkungan
d. Pola penurunan belum diketahui
e. Tidak pernah ditemukan sebagai mutasi de novo
 34
• Pola pewarisan secara matrilineal berkaitan dengan perubahan
organel apa?
a. Lisosom
b. Peroksisom
c. Mitokondria
d. Retikulum endoplasma
e. Komplek Golgi
 • Mitochondrial DNA is inherited maternally in most animals.
• There are diverse mechanisms to eliminate paternal
mitochondria or their DNA in zygotes.
• Paternal mitochondria are degraded by autophagy in C.
elegans or the ubiquitin–mediated mechanism in mammals.
• Paternal mtDNA is degraded by specific nucleases in some
species.
• Paternal mitochondria and/or their mtDNA are physically
excluded prior or on fertilization in some species.
https://www.sciencedirect.com/science/article/pii/S0167488913001092
 Analisa
• Pola pewarisan secara matrilineal berkaitan dengan perubahan
organel apa?
a. Lisosom
b. Peroksisom
c. Mitokondria
d. Retikulum endoplasma
e. Komplek Golgi
 35
• Istilah apa yang menunjukkan variasi alel akibat mutasi
missense?
a. Homozygot
b. Variable number of tandem repeat (VNTR)
c. Single Nukleotide Polymorphism (SNP)
d. Minisatelit
e. Mikrosatelit
 missense mutations
• Clinical management of individuals found to harbor a mutation at a
known disease-susceptibility gene depends on accurate assessment
of mutation-specific disease risk. For missense mutations (MMs)—
mutations that lead to a single amino acid change in the protein
coded by the gene—this poses a particularly challenging problem.
Because it is not possible to predict the structural and functional
changes to the protein product for a given amino acid substitution,
and because functional assays are often not available, disease
association must be inferred from data on individuals with the
mutation. Inference is complicated by small sample sizes and by
sampling mechanisms that bias toward individuals at high familial
risk of disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2311507/
 Analisa
• Istilah apa yang menunjukkan variasi alel akibat mutasi
missense?
a. Homozygot
b. Variable number of tandem repeat (VNTR)
c. Single Nukleotide Polymorphism (SNP)
d. Minisatelit
e. Mikrosatelit
 36
• Seorang ibu sangat sedih ketika mendapatkan bayi yang
dilahirkan meninggal dengan kelainan erythroblastosis faetalis,
anak pertama lahir sehat. Kedua orang tua bayi tersebut
diduga bergolongan darah apa?
a. Ayah A, Rhesus +; Ibu B, Rhesus –
b. Ayah A, Rhesus+ ; Ibu O, Rhesus +
c. Ayah AB, Rhesus -; Ibu O, Rhesus +
d. Ayah B, Rhesus +; Ibu O, Rhesus +
e. Ayah AB , Rhesus-; Ibu O, Rhesus -
 Erythroblastosis fetalis
• Erythroblastosis fetalis, also called hemolytic disease of the
newborn, type of anemia in which the red blood cells
(erythrocytes) of a fetus are destroyed in a maternal immune
reaction resulting from a blood group incompatibility between
the fetus and its mother. This incompatibility arises when the
fetus inherits a certain blood factor from the father that is
absent in the mother. Symptoms of erythroblastosis fetalis
range from mild to severe; death of the fetus or newborn
sometimes results.
https://www.britannica.com/science/erythroblastosis-fetalis
• Two blood group systems, Rh and ABO, primarily are
associated with erythroblastosis fetalis. The Rh system is
responsible for the most severe form of the disease, which can
occur when an Rh-negative woman (a woman whose blood
cells lack the Rh factor) conceives an Rh-positive fetus.
Sensitization of the mother’s immune system (immunization)
occurs when fetal red blood cells that carry the Rh factor (an
antigen in this context) cross the placental barrier and enter
the mother’s bloodstream. They stimulate the production of
antibodies, some of which pass across the placenta into fetal
• It is rare for a mother to become sensitized during the course of her first Rh-
positive pregnancy because the amount of fetal Rh antigen that enters maternal
circulation is insufficient to cause sensitization; usually only during labour will
exposure be significant. However, because Rh sensitivity is likely to develop
during labour, the risk of the disease developing in subsequent Rh-positive
pregnancies increases. The risk can be reduced if the mother receives injections
of Rh immunoglobulin, which destroys fetal red blood cells in her bloodstream,
during her first pregnancy. The fetus also is protected from Rh hemolytic disease
if an ABO blood group incompatibility exists concurrently; protection is conferred
by ABO antibodies, which destroy fetal blood cells in the maternal circulation
before the mother develops Rh sensitivity. Fetal-maternal incompatibilities
within the ABO blood group alone are more common than those of the Rh type,
but the immune reaction is usually much less severe, unless the fetus is type A
and the mother type O.
 Analisa
• Seorang ibu sangat sedih ketika mendapatkan bayi yang
dilahirkan meninggal dengan kelainan erythroblastosis faetalis,
anak pertama lahir sehat. Kedua orang tua bayi tersebut
diduga bergolongan darah apa?
a. Ayah A, Rhesus +; Ibu B, Rhesus –
b. Ayah A, Rhesus+ ; Ibu O, Rhesus +
c. Ayah AB, Rhesus -; Ibu O, Rhesus +
d. Ayah B, Rhesus +; Ibu O, Rhesus +
e. Ayah AB , Rhesus-; Ibu O, Rhesus -
 37
• Apa salah satu kondisi yang memerlukan teorema Bayes dalam
menghitung risiko kekambuhan?
a. Diagnosis etiologi belum ada
b. Pedigri tidak bisa dibuat
c. Kelainan poligenik/multifaktor
d. Kelainan kromosom
e. Data pedigri tidak lengkap
 Bayes’ Rule
• Bayes’ Rule has many analogous forms of varying degrees of apparent complexity. This
paper concerns itself almost entirely with the simplest form, which covers the cases in
which two sets of mutually exclusive possibilities A and B are considered, and where the
total probability in each set is 1. At the end of the paper we will briefly examine how this
most simple case is just a specific case of a more general form of Bayes’ Rule. The simplest
case covers many diagnostic situations, in which the patient either has or does not have a
diagnosable condition (possibility set A) and either has or does not have a set of symptoms
(possibility set B). For such cases, Bayes’ Rule can be used to calculate P(A | B), the
probability that the patient has the condition given the symptom set. Bayes’ Rule says that:
• P(A | B) = P(B | A) P(A) / P(B)
• P(A) is called the marginal or prior probability of A, since it is the probability of A prior to
having any information about B.
• Similarly, the term P(B) is the marginal or prior probability of B. Because it does depend on
having information about B, the term P(A | B) is called the posterior probability of A given B.
The term P(B | A) is called the likelihood function for B given A.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153801/
 analisa
• Apa salah satu kondisi yang memerlukan teorema Bayes dalam
menghitung risiko kekambuhan?
a. Diagnosis etiologi belum ada
b. Pedigri tidak bisa dibuat
c. Kelainan poligenik/multifaktor
d. Kelainan kromosom
e. Data pedigri tidak lengkap
 38
• Manakah yang merupakan sifat sinyal kimia?
A. Sinyal intrasel berupa protein
B. Sinyal kimia disekresi dari suatu sel sebagai tanggapan
terhadap suatu pemicu spesifik
C. Disebut hormone parakrin, bila di edarkan melalui darah
untuk mencapai sel sasaran
D. Neuropeptid termasuk suatu sinyal kimia
E. Sinyal protein dapat menembus membrane plasma untuk
berikatan dengan reseptor
 Chemical signals
• Chemical signals secreted by cells can act over varying distances. In the autocrine signaling
process, molecules act on the same cells that produce them. In paracrine signaling, they act
on nearby cells. Autocrine signals include extracellular matrix molecules and various factors
that stimulate cell growth. An example of paracrine signals is the chemical transmitted from
nerve to muscle that causes the muscle to contract. In this instance, the muscle cells have
regions specialized to receive chemical signals from an adjacent nerve cell. In both autocrine
and paracrine signaling, the chemical signal works in the immediate vicinity of the cell that
produces it and is present at high concentrations. A chemical signal picked up by the
bloodstream and taken to distant sites is called an endocrine signal. Most hormones
produced in vertebrates are endocrine signals, such as the hormones produced in the
pituitary gland at the base of the brain and carried by the bloodstream to act at low
concentrations on the thyroid or adrenal glands. he concentration at which a chemical signal
acts has significance for its target cell. Chemical signals that act at high concentration act
locally and rapidly. On the other hand, chemical signals that act at low concentrations act at
distances and are generally slow.

https://www.britannica.com/science/cell-biology/Gap-junctions#ref313825
 Analisa
• Manakah yang merupakan sifat sinyal kimia?
A. Sinyal intrasel berupa protein
B. Sinyal kimia disekresi dari suatu sel sebagai tanggapan
terhadap suatu pemicu spesifik
C. Disebut hormone parakrin, bila di edarkan melalui darah
untuk mencapai sel sasaran
D. Neuropeptid termasuk suatu sinyal kimia
E. Sinyal protein dapat menembus membrane plasma untuk
berikatan dengan reseptor
 39
• Sel-sel saraf pada jaringan saraf mempunyai gambaran
histologis yang khas yang tidak ditemukan pada sel-sel di
jaringan lain. Apa kekhasan sel tersebut?
A. Mempunyai akson dan dendrit
B. Mempunyai mikrovili
C. Mempunyai kinosilia
D. Mempunyai stereosilia
E. Melekat pada basal lamina
 Analisa
• Nerve fiber = multicellular, containing both an axon and
surrounding myelin sheath. The axon comes from a single
neuron, but the myelin sheath is made by a train of many
myelinating Schwann cells. In the case of unmyelinated axons,
the unmyelinated fiber shares each Schwann cell with several
other unmyelinated axons.
https://web.duke.edu/histology/MoleculesCells/Nerve/Nerve.h
tml
 Analisa
• Composed of axons, Schwann cells, perineurial cells and
fibroblasts in epineurium (outer sheath)
• Perineurium: surrounds each nerve fascicle, is continuous with
pia mater of CNS
• Perineurial cells: derived from fibroblasts; EMA+, S100-
• Schwann cells: neuroectodermally derived cells that resemble
fibroblasts, but strongly S100+, intimately related to axons (by
EM), have continuous basal lamina that coats the cell facing
the endoneurium
https://www.pathologyoutlines.com/topic/softtissuenervenor
mal.html
 Analisa
A. Mempunyai akson dan dendrit
B. Mempunyai mikrovili
C. Mempunyai kinosilia
D. Mempunyai stereosilia
E. Melekat pada basal lamina
 40
• Organel apa yang terlibat dalam kelainan metabolisme
glikosaminoglikan?
A. Lisosom
B. Peroxisom
C. Mitokondria
D. Retikulum endoplasma
E. Komplek Golgi
 Analisa
• Glycosaminoglycans (GAGs) are unbranched, polysaccharide
chains which, with the exception of hyaluronan (HA), are highly
sulphated and constitute the glucidic moieties of proteoglycans
(PGs) macromolecules. Depending on monosaccharide
composition and protein linkage region, as well as sulphation
pattern and degree, GAGs can be grouped in four subfamilies
named chondroitin/dermatan sulphate (CS/DS), heparan
sulphate/heparin (HS/HE), hyaluronan (HA), and keratan
sulphate (KS).
https://www.hindawi.com/journals/bri/2012/245792/
 Analisa
• GAGs contribute to the PGs native folding and functions, as well as to tissue and
organ behavior. In fact, GAGs are involved in stabilization of the fibrillar
extracellular matrix (ECM), control of hydration, regulation of tissue, and
organism development by controlling cell cycle, cell behavior, and differentiation.
HA synthesis is a process carried out on plasma membrane by specific enzymes
called Hyaluronan synthases. The other GAGs chains are polymerized in the ER
and Golgi compartments by specific enzymes drawn close in a complex named
GAGosome. The modification of the synthesis of the GAG portion of PGs or HA
can alter significantly the ECM structure and composition, with multiple effects,
leading to physiological events such as tissue ageing and pregnancy or
pathological events: kidney agenesis, cardiac malformations, abnormal mast
cells, somatic overgrowth, lung dysfunction, chondrodysplasia, tumor
progression, and fibrosis process.

https://www.hindawi.com/journals/bri/2012/245792/
 Analisa
• GAGs are classified into four groups based on core disaccharide
structures. Heparin/heparan sulfate (HSGAGs) and chondroitin
sulfate/dermatan sulfate (CSGAGs) are synthesized in the Golgi
apparatus, where protein cores made in the rough
endoplasmic reticulum are post-translationally modified with
O-linked glycosylations by glycosyltransferases forming
proteoglycans. Keratan sulfate may modify core proteins
through N-linked glycosylation or O-linked glycosylation of the
proteoglycan. The fourth class of GAG, hyaluronic acid is
synthesized by integral membrane synthases which
 Analisa
A. Lisosom
B. Peroxisom
C. Mitokondria
D. Retikulum endoplasma
E. Komplek Golgi
 41
• Sikuen atau urutan apakah yang dapat mengendalikan urutan
asam amino (R-CH (NH2)-COOH) dari deoxyribonucleic acid
(DNA)?
A. Kromatin
B. Kromosom
C. Nukleosom
D. Nukleotida
E. Protein dominan
 Analisa
• Amino acids have the general formula: RCH(NH2)COOH, where
R is a hydrogen atom or an organic group – each of the 20
amino acids has a different organic R group. This R-group is
called the side-chain. Biological amino acids are alpha-amino
acids, which means that both the amine and the carboxylic
acid groups are joined to the same carbon atom (the alpha
atom). Amino acids are white crystalline solids that dissolve in
water (and only dissolve sparingly in organic solvents). It is the
differing chemical properties of the 20 or so amino acids that
gives the protein its chemical and mechanical properties.
 Analisa
• Nucleosomes form the fundamental repeating units of
eukaryotic chromatin, which is used to pack the large
eukaryotic genomes into the nucleus while still ensuring
appropriate access to it (in mammalian cells approximately 2 m
of linear DNA have to be packed into a nucleus of roughly 10
µm diameter).
 Analisa
• A nucleotide is one of the structural components, or building
blocks, of DNA and RNA. A nucleotide consists of a base (one of
four chemicals: adenine, thymine, guanine, and cytosine) plus a
molecule of sugar and one of phosphoric acid.
• A nucleotide is one of the structural components, or building
blocks, of DNA and RNA. A nucleotide consists of a base (one of
four chemicals: adenine, thymine, guanine, and cytosine) plus a
molecule of sugar and one of phosphoric acid.
• More: C, T, and U are called pyrimidines and each has a single
nitrogen-containing ring. A and G are called purines and each has
two nitrogen-containing rings.
https://www.ncbi.nlm.nih.gov/Class/MLACourse/Original8Hour
/Genetics/nucleotide.html
https://www.
ncbi.nlm.nih.
gov/Class/ML
ACourse/Origi
nal8Hour/Ge
netics/nucleo
tide.html
 Analisa
A. Kromatin
B. Kromosom
C. Nukleosom
D. Nukleotida  mengarah kepada asam amino yang tersusun
dalam rantaian DNA
E. Protein dominan
 42
• Manakah pernyataan yang benar untuk suatu penyakit dengan
pola penurunan X-link dominan ?
A. Penyakit muncul di setiap generasi
B. Terdapat konsangunitas
C. Ayah hanya menurunkan penyakit kepada anak lelaki
D. Ibu hanya menurunkan penyakit kepada anak perempuan
E. Jumlah penderita lelaki jauh lebih banyak
 X-linked dominant disease
• As in autosomal dominant inheritance, only one copy of a disease allele on the
X chromosome is required for an individual to be susceptible to an X-linked
dominant disease.
• Both males and females can be affected, although males may be more severely
affected because they only carry one copy of genes found on the X chromosome.
Some X-linked dominant disorders are lethal in males.
• When a female is affected, each pregnancy will have a one in two (50%) chance
for the offspring to inherit the disease allele. When a male is affected, all his
daughters will be affected, but none of his sons will be affected.
• Examples of diseases with X-linked dominant inheritance are hypophosphatemic
ricketsm, oral-facial-digital syndrome type I, and Fragile X syndrome.

http://hihg.med.miami.edu/code/http/modules/education/Des
ign/CoursePageContent.asp?ID=49
 X-linked dominant inheritance
• X-linked dominant
inheritance occurs when
a gene responsible for a
trait or disorder is located
on the X chromosome. The
gene acts in a dominant
manner. This means that
both males and females
can display the trait or
disorder when they have
only one copy of the gene
inherited from a parent
https://www.urmc.rochester.edu/encyclopedia/content.aspx?c
ontenttypeid=90&contentid=p02163
 X-linked dominant inheritance
• Depending on the disorder, a gene that is X-linked dominant
may cause a pregnancy with a male not to survive. Scientists
and doctors say that there is "lethality" in males. This means
that the gene can be passed from mother to daughter, but if
passed to a son, then the pregnancy miscarries. Only those
sons without the gene survive and are born healthy. One
example of an X-linked dominant condition is called
incontinentiahttps://www.urmc.rochester.edu/encyclopedia/content.aspx?c
pigmenti (IP).
ontenttypeid=90&contentid=p02163
 Consanguinity
• Consanguinity ("blood relation", from the Latin consanguinitas
) is the property of being from the same kinship as another
person. In that aspect, consanguinity is the quality of being
descended from the same ancestor as another person.
 Analisa
A. Penyakit muncul di setiap generasi
B. Terdapat konsangunitas
C. Ayah hanya menurunkan penyakit kepada anak lelaki
D. Ibu hanya menurunkan penyakit kepada anak perempuan
E. Jumlah penderita lelaki jauh lebih banyak
 43
• Ny. Sunarto berusia 35 tahun, baru saja melahirkan seorang bayi
yang secara klinis didiagnosis sindroma Down. Tanda-tanda
dimorfik apa yang dimiliki oleh 90% bayi dengan sindroma Down?
A. Profil flat facial
B. Telinga bundar kecil
C. Single palmar crease
D. Loose skin di belakang leher
E. Fisura palpebra yang miring
 Down syndrome
• On physical examination, patients with trisomy 21 have characteristic
craniofacial findings, such as the following:
– Flat occiput and a flattened facial appearance
– Small brachycephalic head
– Epicanthal folds
– Flat nasal bridge
– Upward-slanting palpebral fissures
– Brushfield spots
– Small nose and small mouth
– Protruding tongue
– Small and dysplastic ears
– Generous nuchal skin

https://emedicine.medscape.com/article/943216-clinical#b2
 Down syndrome
• General physical features in patients with Down syndrome may include the
following :
– Shortened extremities
– Short, broad hands, with short fifth finger with hypoplasia of the middle phalanx and
clinodactyly, along with single transverse palmar creases (~60% of patients)
– Joint hyperextensibility or hyperflexibility
– A wide space between the first and second toes (sandal gap)
– Neuromuscular hypotonia
– Diastasis recti
– Dry skin
– Premature aging
– Wide range of intelligence quotients (IQs)
– Congenital heart defects

https://emedicine.medscape.com/article/943216-clinical#b2
 Analisa
A. Profil flat facial
B. Telinga bundar kecil
C. Single palmar crease
D. Loose skin di belakang leher
E. Fisura palpebra yang miring
 44
• Mutagen apakah yang dapat merubah struktur kromosom?
A. Hydroxylamine
B. Proflavin
C. 2-Bromouracil
D. Sinar gamma
E. Sinar UV
 Analisa
• Hydroxylamine can induce any one of the four types of
transition mutations in bacteriophage S13 if the mutagen is
added directly to agar plates seeded with phage and bacterial
indicators. The phage can also be mutated by treating the host
cell with hydroxylamine before infecting it with phage.
https://www.ncbi.nlm.nih.gov/pubmed/14263771
 Analisa
• Proflavine is also known to have a mutagenic effect on DNA by
intercalating between nucleic acid base pairs. It differs from most
other mutagenic components by causing basepair-deletions or
basepair-insertions and not substitutions. In the presence of
light, proflavine can induce double-stranded breaks in DNA.

• 5-Bromouracil (5-BrU, 5BrUra, or br5Ura) is a brominated

derivative of uracil that acts as an antimetabolite or base analog,
substituting for thymine in DNA, and can induce DNA mutation in
the same way as 2-aminopurine
https://www.sciencedirect.com/topics/medicine-and-
dentistry/5-bromouracil
 Analisa
A. Hydroxylamine
B. Proflavin
C. 2-Bromouracil
D. Sinar gamma
E. Sinar UV
 45
• rRNA merupakan ribosomal RNA yang terdiri dari 2 unit yang
pada prokariota memiliki ukuran total berapa?
A. 30 S
B. 40 S
C. 60 S
D. 70 S
E. 80 S
 Ribosomal RNAs
• Ribosomal RNAs constitute 80–90% of total cellular RNAs and
are the essential components (50–60%) of ribosome structure.
Ribosomes (70S in prokaryotes, 80S in eukaryotes) provide the
platform for translation of the genetic code and the link
between genotype and phenotype. Ribosomal RNAs have the
most extensive secondary structure of all RNAs and, by
cooperative interactions with associated proteins, fold into
complex tertiary structures within the ribosome (156, 157). In
contrast to the prokaryotic and eukaryotic rRNAs, protozoan
https://www.sciencedirect.com/topics/neuroscience/ribosomal
rRNAs are derived
-rna by self-splicing
 Prokaryotic rRNAs
• Prokaryotic ribosomes contain three rRNA molecules: 5S (∼120 nt), 16S (∼1.5 kb), and 23S (∼2.9
kb). Together with about 21 different proteins, the 16S rRNA is a part of the small 30S ribosomal
subunit which is the site of codon–anticodon interaction. The 3′ terminus of 16S rRNA is known to
interact with the initiation region of mRNA via the Shine–Dalgarno sequence. Together with about 36
proteins, the 5S and 23S rRNAs constitute the large 50S ribosomal subunit that is thought to be
involved in the regulation of translation accuracy. The 23S rRNA has been proposed to bind the 3′
terminus (–CCA) of tRNA in the ribosomal exit site (E-site) and to promote actively translocation of
tRNA from the P-site. Indeed, there is evidence that the peptidyltransferase activity resides in the
23S rRNA which contains, in its presumed catalytic center, the sequences that are among the most
highly conserved in biology. The catalytic role of 23S rRNA in protein synthesis is further supported
by the demonstration that a Tetrahymena ribozyme can be engineered to express a “modest”
aminoacyl esterase activity catalyzing the hydrolysis of N-formyl-Met from the substrate CAACCA-
fMet.
• All three species of E. coli rRNAs are derived from a single transcript which contains the rRNAs in the
order of 16S-23S-5S. The transcript also contains one or more intermittent tRNAs. In E. coli, there are
seven such rRNA transcription units dispersed throughout the genome and arranged in rrn operons.
The processing of the spacer RNAs between each rRNA and tRNA is carried out by a series of RNases.
https://www.sciencedirect.com/topics/neuroscience/ribosomal
-rna
 Analisa
A. 30 S
B. 40 S  16 S + 23 S
C. 60 S
D. 70 S
E. 80 S
 46
• Mekanisme manakah yang benar tentang cara sitokin
mengatur suatu jejaring tanggapan?
A. Disekresi dari suatu sel sistem endokrin
B. Mengaktifkan transkripsi gen
C. Mempengaruhi aktivitas enzim metabolisme
D. Membunuh mikroorganisme yang menginvasi
E. Reseptor terletak di dalam sitoplasma atau nukleus
 Analisa
• Nuclear receptors (NRs) are a class of proteins responding to
the extra- and intracellular signals carried by steroid or thyroid
hormones to regulate the expression of target genes.
https://www.sciencedirect.com/topics/pharmacology-
toxicology-and-pharmaceutical-science/cell-nucleus-receptor
 Analisa
A. Disekresi dari suatu sel sistem endokrin
B. Mengaktifkan transkripsi gen
C. Mempengaruhi aktivitas enzim metabolisme
D. Membunuh mikroorganisme yang menginvasi
E. Reseptor terletak di dalam sitoplasma atau nukleus
 47
• Manakah yang benar mengenai reseptor membran plasma?
A. Mengandung suatu situs pengikatan spesifik untuk sinyal kimia
tunggal dan situs pengikatan lain yang terlibat dalam transmisi
sinyal
B. Situs pengikatan kedua dapat berinteraksi dengan DNA
C. Dapat mengikat protein chaperon dalam sitoplasma bila tidak
berikatan dengan sinyal
D. Hanya terdiri dari 1 jenis reseptor
E. Disebut juga sebagai faktor transkripsi
 chaperones
• In molecular biology, molecular chaperones are proteins that
assist the conformational folding or unfolding and the
assembly or disassembly of other macromolecular structures.
Chaperones are present when the macromolecules perform
their normal biological functions and have correctly
completed the processes of folding and/or assembly. The
chaperones are concerned primarily with protein folding. The
first protein to be called a chaperone assists the assembly
of nucleosomes from folded histones and DNA and such
1.Richardson RT, Alekseev OM, Grossman G, Widgren EE, Thresher R, Wagner EJ, et al. (July 2006). "Nuclear autoantigenic sperm protein (NASP), a linker histone chaperone that is required for cell

assembly chaperones, especially in the nucleus, are concerned

proliferation". The Journal of Biological Chemistry. 281 (30): 21526–34. doi:10.1074/jbc.M603816200. PMID 16728391.
2.^ Alekseev OM, Richardson RT, Alekseev O, O'Rand MG (May 2009). "Analysis of gene expression profiles in HeLa cells in response to overexpression or siRNA-mediated depletion of
NASP". Reproductive Biology and Endocrinology. 7: 45. doi:10.1186/1477-7827-7-45. PMC 2686705. PMID 19439102.
3.^ Ellis RJ (July 2006). "Molecular chaperones: assisting assembly in addition to folding". Trends in Biochemical Sciences. 31 (7): 395–401
 Analisa
• Amino acid derived hormones and polypeptide hormones are not lipid-derived
(lipid-soluble) and therefore cannot diffuse through the plasma membrane of
cells. Lipid insoluble hormones bind to receptors on the outer surface of the
plasma membrane, via plasma membrane hormone receptors. Unlike steroid
hormones, lipid insoluble hormones do not directly affect the target cell because
they cannot enter the cell and act directly on DNA. Binding of these hormones to
a cell surface receptor results in activation of a signaling pathway; this triggers
intracellular activity and carries out the specific effects associated with the
hormone. In this way, nothing passes through the cell membrane; the hormone
that binds at the surface remains at the surface of the cell while the intracellular
product remains inside the cell. The hormone that initiates the signaling pathway
is called a first messenger, which activates a second messenger in the cytoplasm

https://courses.lumenlearning.com/wm-
biology2/chapter/plasma-membrane-hormone-receptors/
 Analisa
• Second messengers are molecules that relay signals received
at receptors on the cell surface — such as the arrival of protein
hormones, growth factors, etc. — to target molecules in the
cytosol and/or nucleus.
 Analisa
A. Mengandung suatu situs pengikatan spesifik untuk sinyal
kimia tunggal dan situs pengikatan lain yang terlibat dalam
transmisi sinyal
B. Situs pengikatan kedua dapat berinteraksi dengan DNA 
tidak disebutkan secara spesifik DNA
C. Dapat mengikat protein chaperon dalam sitoplasma bila tidak
berikatan dengan sinyal  tidak ada data mendukung
D. Hanya terdiri dari 1 jenis reseptor
E. Disebut juga sebagai faktor transkripsi  meregulasi sitokin
 48
• Manakah dari peristiwa ini yang bukan merupakan penurunan
non Mendelian?
A. Alel letal
B. Poligen
C. Pleotropi
D. Kriptomeri
E. Multifaktor
 Non-Mendelian genetics
• Non-Mendelian genetics are basically any inheritance patterns that
don’t follow one or more laws of Mendelian genetics. Let’s review
those laws quickly:
– Mendel’s First Law (Law of Segregation) – A parent who has two alleles for
a gene can only pass on one allele or the other to each offspring.
– Mendel’s Second Law (Law of Independent Assortment) – Two or more
traits are inherited separately from each other; they don’t always occur
together.
– Mendel’s Third Law (Law of Dominance) – One dominant allele will take
charge over a recessive allele and “mask” it. The only way recessive alleles
can be seen is if an individual possesses two copies of the recessive allele.
https://untamedscience.com/biology/genetics/non-mendelian-
genetics/
 Non-Mendelian genetics
• These are the basic rules of Mendelian genetics, but as scientists began exploring more and more
test crosses, they found tons of traits that didn’t match up nicely with what these laws predicted.
• Some traits exhibited a kind of blending, where the offspring of organisms with two different traits
didn’t have one or the other form from the parents—they had something that was sort of in the
middle. This implies that certain alleles aren’t dominant over the other ones. Rather, they share
roles like harmonious friends.
• Some traits seemed to be controlled by complex inheritance patterns. We know now that traits can
be controlled by more than one gene, or genetic material may pass down from parent to offspring in
different ways than what Mendel predicted with his Law of Segregation.
• Finally, non-Mendelian inheritance patterns might just be caused by mistakes in reproduction. There
are a ton of different processes all happening together, like a coordinated dance, and all it takes is
one thing to trip or mess up and the whole thing goes haywire. There’s so many things that could go
wrong that frankly it’s a wonder that we all end up here in one piece
 Analisa
• Pleiotropic: Producing or having multiple effects from a single gene. For
example, the Marfan gene is pleiotropic, potentially causing such diverse
effects as long fingers and toes (arachnodactyly), dislocation of the lens of
the eye, and dissecting aneurysm of the aorta.

• Polygenic inheritance occurs when one characteristic is controlled by two

or more genes
• Polygenic inheritance. Some characteristics are polygenic, meaning that
they’re controlled by a number of different genes. In polygenic inheritance,
traits often form a phenotypic spectrum rather than falling into clear-cut
categories.
 Analisa
• A cross between two heterozygous yellow mice produces
yellow and brown mice in a ratio of 2:12:12, colon, 1,
not 3:13:13, colon, 1. This is an example of lethality, in which a
particular genotype makes an organism unable to survive.
https://www.khanacademy.org/science/high-school-
biology/hs-classical-genetics/hs-non-mendelian-
inheritance/a/pleiotropy-lethal-alleles-and-sex-linkage
 Analisa
A. Alel letal
B. Poligen
C. Pleotropi
D. Kriptomeri  tidak di bahas dalam non mendel
 remaining unexpressed in the phenotype unless activated by
another factor
E. Multifaktor
 49
• Pernyataan manakah yang benar mengenai gene rearrangement?
A. Gene rearrangement terjadi pada tingkat DNA dan mekanismenya
terjadi sebelum dimulai proses transkripsi
B. Gene rearrangement terjadi situs spesifik yang disebut RSSs
C. Terjadinya gene rearrangement dikatalis oleh gen RAG1 dan RAG2
D. Gene rearrangement bisa terjadi pada semua gen pada semua
spesies
E. Gene rearrangement merupakan proses pengaturan gen yang
berguna sebagai bentuk penyesuaian diri terhadap lingkungan
 Analisa
• In genetics, a chromosomal rearrangement is a mutation that
is a type of chromosome abnormality involving a change in the
structure of the native chromosome. Such changes may involve
several different classes of events, like deletions, duplications,
inversions, and translocations.
 RSS
• Recombination signal sequences are conserved
sequences of noncoding DNA that are recognized by
the RAG1/RAG2 enzyme complex during V(D)J
recombination in immature B cells and T cells. Recombination
signal sequences guide the enzyme complex to the V, D, and J
gene segments that will undergo recombination during the
formation of the heavy and light-chain variable regions in T-cell
receptors and immunoglobulin molecules
 Gene rearrangement
• Gene rearrangement is a phenomenon in which a programmed DNA
recombination event occurs during cellular differentiation to reconstitute a
functional gene from gene segments separated in the genome. The most studied
cases of gene rearrangement are the antigen receptor (immunoglobulin and T-
cell receptor) genes in vertebrate lymphocytes. The coding-sequences for the
variable regions of the antigen receptor are split into V (variable), D (diversity),
and J (joint) segments. In developing lymphocytes, the V(D)J segments are
combined through DNA recombination reactions, depending on RAG1/RAG2
(recombination-activating genes) and DNA repair proteins. This process
generates antigen receptor diversity that allows adaptive immune defense
against a large variety of pathogens. Gene rearrangement also plays crucial
developmental roles in prokaryotes: nitrogen fixation in heterocysts of the
cyanobacterium Anabaena spp. and sporulation in spore-forming bacteria

https://academic.oup.com/nar/article/45/11/6669/3848393
 Analisa
A. Gene rearrangement terjadi pada tingkat DNA dan
mekanismenya terjadi sebelum dimulai proses transkripsi
B. Gene rearrangement terjadi situs spesifik yang disebut RSSs
C. Terjadinya gene rearrangement dikatalis oleh gen RAG1 dan
RAG2
D. Gene rearrangement bisa terjadi pada semua gen pada semua
spesies
E. Gene rearrangement merupakan proses pengaturan gen yang
berguna sebagai bentuk penyesuaian diri terhadap lingkungan
 50
• Seorang ibu sangat sedih ketika mendapatkan bayi yang
dilahirkan meninggal dengan kelainan erythroblastosis faetalis,
anak pertama lahir sehat. Apa penyebab terjadinya kondisi ini?
A. Kelainan herediter pada bayi
B. Inkompatibilitas faktor Rhesus anak dan ibu
C. Inkompatibilitas golongan darah ABO
D. Penyakit autoimun pada ibu
E. Penyakit infeksi pada ibu
 erythroblastosis fetalis
• The adult human body is home to trillions of red blood cells, also known as
RBCs or erythrocytes. These blood cells carry oxygen, iron, and many other
nutrients to the appropriate places in the body. When a woman is
pregnant, it’s possible that her baby’s blood type will be incompatible with
her own. This can cause a condition known as erythroblastosis fetalis,
where the mother’s white blood cells (WBCs) attack the baby’s RBCs as
they would any foreign invaders. This condition is highly preventable and
the typical, severe form is now very rare in developed countries. Catching it
early can ensure a successful pregnancy for mother and child. If left
untreated, however, it can be life-threatening for the baby. Erythroblastosis
fetalis is now known as hemolytic disease of the newborn.

https://www.healthline.com/health/erythroblastosis-
fetalis#symptoms
 What causes erythroblastosis fetalis?
• There are two main causes of erythroblastosis fetalis: Rh
incompatibility and ABO incompatibility. Both causes are associated
with blood type. There are four blood types:
– A
– B
– AB
– O
• In addition, blood can be either Rh positive or Rh negative. For example, if
you’re type A and Rh positive, you have A antigens and Rh factor antigens
on the surface of your RBCs. Antigens are substances that trigger an
immune response in your body. If you have AB negative blood, then you
have both A and B antigens without the Rh factor antigen.
 Rh incompatibility
• Rh incompatibility occurs when a Rh-negative mother is
impregnated by a Rh-positive father. The result can be a Rh-positive
baby. In such a case, your baby’s Rh antigens will be perceived as
foreign invaders, the way viruses or bacteria are perceived. Your
blood cells attack the baby’s as a protective mechanism that can
end up harming the child. If you’re pregnant with your first baby,
Rh incompatibility isn’t as much of a concern. However, when the
Rh-positive child is born, your body will create antibodies against
the Rh factor. These antibodies will attack the blood cells if you
ever become pregnant with another Rh-positive baby.
 ABO incompatibility
• Another type of blood type mismatch that can cause maternal
antibodies against her baby’s blood cells is ABO
incompatibility. This occurs when the mother’s blood type of A,
B, or O isn’t compatible with the baby’s. This condition is
almost always less harmful or threatening to the baby than Rh
incompatibility. However, babies can carry rare antigens that
can put them at risk for erythroblastosis fetalis.
 symptoms
• Babies who experience erythroblastosis fetalis symptoms may appear
swollen, pale, or jaundiced after birth. A doctor may find that the baby
has a larger-than-normal liver or spleen. Blood tests can also reveal that
the baby has anemia or a low RBC count. Babies can also experience a
condition known as hydrops fetalis, where fluid starts to accumulate in
spaces where fluid is normally not present. This includes spaces in the:
– abdomen
– heart
– lungs
• This symptom can be harmful because the extra fluid places pressure on
the heart and affects its ability to pump.

https://www.healthline.com/health/erythroblastosis-
fetalis#symptoms
 Analisa
A. Kelainan herediter pada bayi
B. Inkompatibilitas faktor Rhesus anak dan ibu
C. Inkompatibilitas golongan darah ABO
D. Penyakit autoimun pada ibu
E. Penyakit infeksi pada ibu