2 - Genetics (BusySPR 2016 SBAs) PDF

This Copy is for Dr.
Mohamed ElHodiby
BASIC PRINCIPLES
Question 1 Which fetal tissue is not typically used for karyotyping?

A Fetal lymphocytes B Fetal red blood cells
C Amniocytes D Chorionic villus cells
E Fetal skeletal muscle cells
A(Correct answer: B)
Explanation
KARYOTYPING
· Utilises peripheral blood lymphocytes and can still be performed on samples
received in the lab >24h after sampling. Can also be performed on chorionic villi, fetal
cells from amniotic fluid and fetal blood following fetal blood sampling
· Skin and skeletal muscle can also be used after a still birth
· Red cells do not have a nucleus and cannot be used for karyotyping.
A 23 year old woman has undergone chorionic villus sampling

at 13 weeks gestation following a ‘high risk’ result from the
Question 2
combined test. She should be informed that the results will be
available
A Within 24h B In 24-48h

C In 48-72h D In 1-2 weeks
In 2-3 weeks
E
A(Correct answer: C)
Explanation
Karyotype results available within 48-72h from fetal blood and chorionic villi but in 2-3 weeks
from amniotic fluid
This Copy is for Dr. Mohamed ElHodiby

A 23 year old woman has undergone amniocentesis at 16 weeks
Question 3 gestation following a ‘high risk’ result from the quadruple test. She
should be informed that the results will be available
A Within 24h B In 24-48h

C In 48-72h D In 1-2 weeks
E In 2-3 weeks
A(Correct answer: E)
Explanation
 Karyotype results available within 48-72h from fetal blood and chorionic villi but in 2-3
weeks from amniotic fluid
Question 4 For karyotype to be undertaken from peripheral blood
A Cell division is inhibited using antibiotics B Cell division is arrested in anaphase

Cell division is arrested in metaphase using Cell division is arrested during telophase
C D
colchicine using colchicine
Cell division is arrested during prophase
E
using colchicine
Explanation
 Cell division is arrested in metaphase by the addition of colchicine which prevents
spindle formation
 Chromosomes are typically stained with Giemsa (G-banding). The banding pattern of
each chromosome is characteristic with the dark bands containing mainly INACTIVE
genes
 Other banding patterns can be obtained using quinacrine (Q banding, visualised by
ultraviolet light), C-banding to show highly repetitive micro-satellite repeat DNA at the
centromeres
 Banding allows the identification of missing or additional chromosomal material of at
least 4,000kb
Question 5 Karyotyping
Cannot be used to identify chromosome
A Can be used to detect gene mutations B
translocations
Can be used in the pre-natal diagnosis of sickle
C D Can be used to identify gene deletions
cell disease
E Typically uses Giemsa staining

Explanation
Same as of Question 4
Question 6 Chromosome heteromorphism

A Is greatest in the X chromosome B Is greatest in chromosome 21
C Does not occur in humans D Only occurs in acrocentric chromosomes
E Is greatest in the Y chromosome
Explanation
CHROMOSOME HETEROMORPHISMS
 These are variations in the amount of DNA present in particular chromosomes from
different individuals caused by variations in the size of repetitive DNA - they are
inherited rather than acquired
 The Y chromosome shows the greatest variation while the X chromosome shows the
least variation
There are 4 main groups of heteromorphisms
1) The size of Yq (long arm of Y chromosome) - 10% of normal males have a Yq
which is obviously shorter or longer than usual
2) Size of centromeric heterochromatin
3) Satellite polymorphisms - variations in the size of the satellite in acrocentric
chromosomes (13-15, 21, 22). Metacentric chromosomes do not have satellites
4) Fragile sites - constriction sites other than the centromere which are prone to
breakage. There are at least 80 common fragile sites. Most are not associated with any
clinical syndrome except the fragile site at Xq27.3 which is associated with learning
disability
Question 7 With respect to the structure of DNA

A DNA contains the base uracil B Nucleotides contain a nitrogenous base
Phosphate groups are found in RNA but not
C Nucleotides do not contain sugar molecules D
DNA
Bases are held together by 3-5-phosphodiester
E
bonds

Explanation
DNA STRUCTURE
· Nucleic acids (DNA or RNA) are made up of a chain of nucleotides
· Each nucleotide contains a nitrogenous base, a sugar molecule and a phosphate
group
· The base is either a purine (adenine and guanine) or a pyrimidine (cytosine,
thymine and uracil)
· Thymine occurs in DNA only while uracil occurs only in RNA *
· The sugar molecule is either ribose (RNA) or deoxyribose (DNA) and they are
held together by 3-5- phosphodiester bonds *
· The DNA molecule is made up of two chains of nucleotides held together by
hydrogen bonds between the bases
· A purine in one chain is always paired to a pyrimidine in the other chain: A-T; G-C
*
· The chain end terminated by the 5' carbon of the sugar molecule is the 5' end and
this always lies opposite the 3' end of the other strand. The two chains are arranged in a
double helix
Question 8 With respect to the structure of DNA, which base pairing is correct?
A U-T B A-T
C G-T D G-A
E U-G
Explanation
Question 9 With respect to the structure of nucleic acids
A Thymine occurs in DNA but not RNA B Uracil occurs in DNA and RNA
C Cytosine occurs in RNA but not DNA D Uracil is always paired to Thymine in RNA
E Both cytosine and Thymine occur in RNA
A(Correct answer: A)
Explanation

Question 10 DNA replication
A Occurs during transcription B Occurs during translation
Occurs with the new DNA chain synthesized in the

C Is semi-conservative D
3 prime to 5 prime direction
Requires separation of the double helix by DNA

E
polymerase
Explanation
DNA REPLICATION
· Occurs during the S (synthesis) phase of the cell cycle

· The double helix is separated by the enzyme DNA helicase at different sites on
the DNA molecule
· DNA synthesis is undertaken by DNA polymerase in the 5' to 3' direction
· The leading strand is synthesised as a continuous chain while the lagging strand
is synthesised in pieces called Okazaki fragments and then joined by DNA ligase
· Only one chain of the double helix is newly synthesised and DNA replication is
therefore semiconservative *
· Transcription is the synthesis of mRNA from DNA
Question 11 DNA polymerase
A Separates the double helix during DNA replication B Synthesizes the new DNA chain
C Digests the DNA molecule D Synthesizes RNA from DNA
E Synthesizes DNA from RNA
Explanation

Question12 With respect to the structure of chromosomes
The DNA double helix is coiled around spherical

A One in three chromosomes do not have a centromere B
histone beads to form nucleosomes
The DNA double helix coils around non-histone Chromatine fibres are coiled around histone beades
C D
proteins to form chromatin fibres to form the chromosome
The centromere is formed from chromatin fibres coiled

E
around the DNA double helix
Explanation
CHROMOSOME STRUCTURE
· Primary coiling of DNA into double helix
· Secondary coiling of double helix around spherical histone beads to form
nucleosomes
· Tertiary coiling of nucleosomes to form chromatin fibres
· Chromatine fibres form loops on a scaffold of non-histone acidic protein
· Chromatin fibres are wound into a tight coil to form chromosome
· All chromosomes have a centromere, the site of attachment of the spindle
apparatus during cell division
Question 13 Reciprocal translocations

A Are also called Robertsonian translocations B Usually involve acrocentric chromosomes
C Most commonly involve chromosome 21 D Are always balanced
Carry a 1-10% risk of phenotypic abnormality in
E
the individual
Explanation
RECIPROCAL TRANSLOCATIONS
· Result from breakage of at least two metacentric chromosomes (centromere in the
middle) with exchange of genetic material
· Long arms of chromosomes 11 and 22 more commonly involved
· Incidence in general population ~1:500
· The total number of chromosomes is maintained at 46

· Individual with balanced reciprocal translocation phenotypically normal.
Segregation at meiosis may result in off-spring inheriting an unbalanced chromosomal
complement, resulting in an increased risk of miscarriage or congenital anomalies
· Risk of abnormal off-spring dependent on the particular chromosomal
rearrangement but lies between 1-10%
A 23 year old woman and her 24 year old partner have been referred for
Question 14
genetic counseling. One of them carries a 13q 21q balanced translocation.
If the male is the carrier of the translocation, his
If the female is the carrier of the translocation, all her
A B offspring have a 1-3% risk of having Down’s
offspring will have Down’s syndrome
syndrome
The risk of Down’s syndrome in their offspring is All pregnancies will have an abnormality because of
C D
identical regardless of the sex of the carrier an autosomal monosomy
There is no increase in risk because the translocation

E
is balanced
Explanation
ROBERTSONIAN TRANSLOCATION
· Results from breakage of two acrocentric chromosomes (13,14,15,21,22) at or
close to the centromere with fusion of the long arms and (usually) a loss of the short
arms
· Total number of chromosomes reduced to 45. Short arms usually contain only
ribosomal RNA genes with multiple copies on other acrocentric chromosomes
· Incidence 1:1,000
· 13q14q translocations most common
· Increased risk of miscarriage / fetal anomaly in carriers of balanced Robertsonian
translocations
· Female carriers of 13q21q or 14q21q Robertsonian translocations have a 10%
risk of having a baby with Down syndrome while male carriers have a 1-3% risk
· 21q21q balanced translocation carriers have a 100% risk of a live birth with Down
syndrome (monosomy 21 which is the other possibility is not compatible with live birth)

Question 15 Autosomal dominant traits / conditions
Are expressed in homozygous but not

A B Affect males more often than females
heterozygous individuals
Tend to have the same disease severity in

C Have a vertical pedigree pattern D
different individuals
Typically have a maternal age effect with respect

E
to the incidence of new mutations
Explanation
AUTOSOMAL DOMINANT INHERITANCE
· The trait / condition is expressed in heterozygous individuals *
· Males and females affected in equal numbers *
· Vertical pedigree pattern - does not skip generations *
· Males and females can transmit the condition to their male / female off-spring *
· Unaffected individuals cannot transmit the disease (the exception is in conditions
with variable or non-penetrance - where individuals with the mutant allele have a normal
phenotype but can transmit the condition) *
· Show variable expressivity - both in terms of severity of the condition and age of
onset
· Affected individuals have a 1 in 2 risk of their offspring being affected *
· There is a paternal age effect with respect to the incidence of new mutations
· Examples include: otosclerosis, von Willebrand disease, familial
hypercholesterolaemia, Huntington’s disease, Tuberous sclerosis, Myotonic dystrophy,
Neurofibromatosis, Hereditary spherocytosis, familial polyposis coli *
Question 16 Which disease is not an autosomal dominant condition?

A Myotonic dystrophy B Hereditary spherocytosis
C Alpha thalassaemia D Von Willebrand’s disease
E Tuberous sclerosis
Explanation
Examples of autosomal dominant conditions include: otosclerosis, von Willebrand
disease, familial hypercholesterolaemia, Huntington’s disease, Tuberous sclerosis,
Myotonic dystrophy, Neurofibromatosis, Hereditary spherocytosis, familial polyposis coli
· If woman has Von Willebrand’s disease there is a 1 in 2 chance that her offspring
would inherit the disease regardless of sex

A 24 year old woman attends the antenatal clinic at 10 weeks gestation. She
Question 17 is known to have Von Willebrand’s disease.
There is a 1 in 2 chance that her offspring would There is a 1 in 2 chance that her offspring would be a
A B
inherit the disease carrier of the disease
If she is carrying a male fetus, there is a 100% chance If she is carrying a female fetus, there is a 1 in 2
C D
that he would inherit the disease chance that she would be a carrier of the disease
E Her partner should be tested for the disease
Explanation
Question 18 Autosomal dominant conditions
Are transmitted from male to female and from

A Have a horizontal pedigree pattern B
female to male
The offspring of an affected individual will either The offspring of an affected individual have a 1 in 4
C D
have the condition or be a carrier chance of having the condition
The offspring of an affected individual will either
E
inherit the condition or be normal
Explanation
AUTOSOMAL DOMINANT INHERITANCE
· The trait / condition is expressed in heterozygous individuals *
· Males and females affected in equal numbers *
· Vertical pedigree pattern - does not skip generations *
· Males and females can transmit the condition to their male / female off-spring *
· Unaffected individuals cannot transmit the disease (the exception is in conditions
with variable or non-penetrance - where individuals with the mutant allele have a normal
phenotype but can transmit the condition) *
· Show variable expressivity - both in terms of severity of the condition and age of
onset
· Affected individuals have a 1 in 2 risk of their offspring being affected *
· There is a paternal age effect with respect to the incidence of new mutations


Question 19 Which one is not an autosomal recessive condition?
A Sickle cell disease B Cystic fibrosis
C Phenylketonuria D Huntington’s disease
E Adrenogenital syndrome
A(Correct answer: D)
Explanation
Examples of autosomal recessive conditions include: Cystic fibrosis, sickle cell disease,
phenylketonuria, adrenogenital syndrome, mucopolysaccharidoses, spinal muscular
atrophy
Circumstances in which females can be affected by X-linked recessive conditions

Question 20 include
A When their father is a carrier of the condition B The effect of variable penetrance
C The effect of variable expressivity D The effect of atypical lyonisation
E If the woman has an autosomal monosomy
Explanation
Females can be affected by X-linked recessive conditions due to
· Atypical lyonisation - random inactivation of (predominantly) the normal X
chromosome *
· X-autosome translocation under which circumstances the normal X chromosome
is preferentially inactivated (otherwise an autosomal monosomy would result) *
· Turner syndrome (45X) *
· A new mutation on the second X chromosome *

Question 21 Monozygotic twins
Are associated with an increased risk of Down’s
A Are more common in West-Africans B
syndrome
C Account for 1 in 80 pregnancies D Are always monochorionic
Are associated with an increased risk of congenital
E
anomalies

Explanation
MONOZYGOTIC TWINS
· Result from the fertilisation of one oocyte by one sperm, the resulting zygote
splitting into two during the early stages of development
· Incidence ~1:300 - constant worldwide
· Are genetically identical and therefore of the same sex
· 70% are monochorionic and diamniotic and 30% are dichorionic and diamniotic.
Monochorionic monoamniotic twins are rare
· Twin pregnancies are associated with an increased risk of congenital anomalies
(monozygotic twins in particular) but there is no increased risk of aneuploidy
Question 22 Fluorescent in-situ hybridization
Uses fluorescently labeled gene-specific DNA

A Uses cells in metaphase B
sequences
C Can only test for 3 chromosomes simultaneously D Can test for 46 chromosomes simultaneously
Cannot be used in Down’s syndrome screening

E
programs
Explanation
Fluorescence in-situ hybridisation (FISH)
• Uses non-dividing (interphase) cells in uncultured samples
• Fluorescently labelled chromosome-specific DNA sequences are used to identify
chromosome copy number
• Three chromosomes can be detected at the same time (three flurochromes
available - red, blue and green)
• Commercial kits are available for FISH and this is therefore a relatively inexpensive
technique
• Designed to detect specific aneuploidies and will not detect other abnormalities or
structural chromosomal defects
• False positive rate less than 1 in 30,000 cases
• False negative rate less than 1 in 4000 cases
• Misdiagnosis may be due to:
1) Maternal cell contamination - this will not be detectable if the fetus is female.
2) Structural chromosome anomalies
3) DNA polymorphism causing cross-hybridisation of DNA probe with other DNA
locations

4) Mosaicism - this may only be detected if a sufficient cells (at least 100) are used for
analysis
Question 23 The false positive rate of fluorescent in-situ hybridization is
A 1 in 200 B 1 in 400
C 1 in 1000 D 1 in 10,000
E 1 in 30,000
Explanation
Question 24 Which material / cells are used for fluorescent in-situ hybridization?
A Dividing (metaphase) cells B Non-dividing (interphase) cells
C Extracted DNA D Extracted RNA
E Extracted protein
Explanation
Question 25 Quantitative fluorescent PCR (QF-PCR)
Can be used to determine the expression of

A B Can be used to diagnose Down’s syndrome
specific proteins
C Cannot be used to diagnose Turner’s syndrome D Relies on the amplification of RNA sequences
E Relies on the amplification of RNA sequences
Explanation
Polymerase Chain Reaction (PCR)
• Uses quantitative fluorescence PCR (QF-PCR)

• The number of copies of a particular chromosome is determined using DNA
analysis
• Relies on the analysis of non-coding regions of DNA which show a wide variation in
size between different individuals
• These regions are amplified by PCR and separated on a gel according to size
• If three copies are present of different sizes, this is easily detectable by differences
in migration on the gel
• If two copies are present of identical size, this will also be detectable because the
total quantity of DNA can also be determined
• QF-PCR requires semi-automated equipment which may not be available in many
cytogenetics labs and the system has to be validated in every centre. However, once
established, costs compare favourably with FISH
• Maternal cell contamination and mosaicism can be detected
• Failure of DNA amplification occurs in about 0.1% of samples
• Will not detect abnormalities in other chromosomes (apart from those analysed) or
structural anomalies
• QF-PCR is not reliable when used to analyse a single cell and FISH is the preferred
method for pre-implantation genetic diagnosis
Question 26 Pre-implantation genetic diagnosis

Can be undertaken in women undergoing intra- Cannot be undertaken in women undergoing intra-
A B
uterine insemination cytoplasmic sperm injection (ICSI)
Requires biopsy of the embryo at the 2 or 4 cell Requires biopsy of the embryo at the 6-10 cell
C D
stage stage
Requires biopsy of the embryo at the 16-32 cell
E
stage
Explanation
PRE-IMPLANTATION GENETIC DIAGNOSIS (PGD)
• This requires IVF with biopsy of the embryo at the 6-10 cell stage. The indications
are as an alternative to pre-natal diagnosis in a couple known to be at risk of
transmitting a genetic disorder. It can also be used as a primary tool in couples
undergoing IVF treatment.

Question 27 Which cells are not used for pre-implantation genetic diagnosis?
A Polar body from oocyte B Polar body from zygote
C Inner cell mass cells D Blastomeres from cleavage stage embryo
E Trophectoderm cells
Explanation
BIOPSY FOR PRE-IMPLANTATION DIAGNOSIS

Uses the following cells:
• Polar body from oocyte or zygote
• Blastomeres from cleavage stage embryos
• Trophectoderm cells from blastocysts - however, up to 60% of human embryos
arrest in culture and do not reach the blastocyst stage. Blastocyst biopsy gives more
cells for diagnosis but less time as the blastocyst would have to be transferred into the
uterus as soon as possible
• Most centres use cleavage stage embryo biopsy. There are no reports of blastocyst
biopsy / use of inner cell mass cells.
Question 28 During pre-implantation genetic diagnosis, allele drop-out can result in

A Culture failure B DNA amplification failure
False positive diagnosis of for autosomal recessive
C False positive diagnosis of Down’s syndrome D
condition
False negative diagnosis for an autosomal dominant
E
condition
Explanation
PCR PROBLEMS
• Contamination by DNA from the environment, laboratory staff and other cells
including sperm and cumulus cells - for this reason, ICSI(Intra-Cytoplasmic
Sperm Injection) is used prior to pre-implantation genetic diagnosis
• Allele drop-out: This is the preferential amplification of one allele only and is
particularly important in autosomal dominant conditions. If the mutated allele
drops out, the embryo would be erroneously diagnosed as normal.

Question 29 Pre-implantation genetic diagnosis
A Is typically undertaken following conventional IVF B Usually requires intra-cytoplasmic sperm injection
C Cannot be used to diagnose cystic fibrosis D Is associated with an increased risk of miscarriage
Is associated with an increased risk of congenital

E
anomalies
Explanation
PCR PROBLEMS
• Contamination by DNA from the environment, laboratory staff and other cells
including sperm and cumulus cells - for this reason, ICSI(Intra-Cytoplasmic
Sperm Injection) is used prior to pre-implantation genetic diagnosis
• Allele drop-out: This is the preferential amplification of one allele only and is
particularly important in autosomal dominant conditions. If the mutated allele
drops out, the embryo would be erroneously diagnosed as normal.
• Pre-implantation genetic diagnosis is not associated with an increased risk of
miscarriage or congenital anomalies
Question 30 The proportion of human pre-implantation embryos that show mosaicism is

A Up to 1% B Up to 5%
C Up to 8% D Up to 18%
E Up to 50%
Explanation
MOSAICISM AND PRE-IMPLANTATION DISGNOSIS
• Up to 50% of human pre-implantation embryos show mosaicism, the commonest
abnormalities being haploid and tetraploid nuclei
• It is now recognised that 1-2 cells biopsied from the blastocyst are not necessarily
representative of the rest of the embryo
• Mosaicism does not affect sexing as female cells would have to appear in a male
embryo (or vice versa)

Question 31 Okazaki fragments
Are joined by DNA ligase to produce a continuous
A Are produced during RNA synthesis B
DNA molecule
C Are produced by DNA helicase D Are produced after enzyme digestion of DNA
E Are produced after enzyme digestion of RNA
Explanation
DNA REPLICATION
the DNA molecule
Question 32 With respect to the structure of chromosomes
A The short arm of chromosome is the q arm B Metacentric chromosomes have no centromere
Acrocentric chromosomes are usually involved in

C Metacentric chromosomes to not contain histones D
balanced translocations
E Acrocentric chromosomes do not have a centromere
Explanation
METACENTRIC - have the centromere in the middle (1,3,16,19,20)
· ACROCENTRIC - have the centromere close to one end (13,14,15,21, 22) -these
are the chromosomes usually involved in balanced translocations *
· SUB-METACENTRIC - have centromere in-between
· Chromosomes have a short (p = petit) and a long (q) arm??

Question 33 Non-dysjunction
Occurs during meiosis but does not occur during Occurring during meiosis I results in the gamete
A B
mitosis receiving both homologues of the chromosome pair
Occurring in meiosis II results in the gamete

C D Occurs during prophase
receiving both homologues of the chromosome pair
E Accounts for 1-3% of cases of Down’s syndrome
Explanation
NON-DYSJUNCTION
· Failure of the chromosomal bivalents to segregate to the two daughter cells during
anaphase - can occur during meiosis I & II or during mitosis
· Occurring during meiosis I - the gamete receives both homologues of the
chromosome pair
· Occurring during meiosis II - the gamete receives two copies of one of the
homologues of the chromosome pair
· The majority of autosomal trisomies result from non-dysjunction during one of the
maternal meiotic division. The other daughter gamete inherits an autosomal monosomy
- always incompatible with survival to term
· Increased risk of non-dysjunction with increasing maternal age
A 33 year old woman attends the antenatal clinic at 10 weeks gestation.

She is a carrier of cystic fibrosis and her partner is also a carrier of cystic
Question 34
fibrosis.
All their children will either have cystic fibrosis or There is a 1 in 2 chance that her offspring will
A B
be carriers have cystic fibrosis
There is a 3 in 4 chance that her offspring will not There is a 1 in 2 chance that her offspring will
C D
have cystic fibrosis neither have the disease nor be a carrier
If the woman and her partner have different gene

E
mutations then all their children will be unaffected
Explanation
· Autosomal recessive condition
· Woman and her partner have one abnormal allele

· 1 in 4 chance that an offspring inherits 2 normal alleles and 1 in 2 chance that
they inherit one normal allele (carrier). Carriers do not have the disease so 3 in 4
chance that offspring will not have the disease
Question 35 X-linked recessive conditions
A Mainly affect females B Cannot be transmitted from men to their sons
C Cannot be transmitted from women to their sons D Show a horizontal pedigree pattern
E Show a vertical pedigree pattern
Explanation
X-LINKED RECESSIVE INHERITANCE
· Males are affected predominantly *
· Male-male transmission never occurs. Unaffected males never transmit the
condition *
· Affected males transmit the allele to their daughters who become heterozygous
carriers and are almost always unaffected. Lyonisation (random inactivation of one X
chromosome) may result in some females having mild symptoms *
· Knight’s move pedigree pattern *
· The severity of the disease is uniform across generations *
· A woman with an affected son and an affected brother is an obligate carrier as the
possibility of two independent new mutations is extremely small. A woman with one
affected son is not an obligate carrier *
· Examples include: red-green colour blindness, Duchenne / Becker muscular
dystrophy, Haemophilia A / B, X-linked agammaglobulinaemia *

sequences

E
programs

Explanation
technique
locations
analysis
A 1 in 200 B 1 in 400
C 1 in 1000 D 1 in 10,000
E 1 in 30,000
Explanation
Question 38 Fluorescent quantitative polymerase chain reaction (QF-PCR)
Amplifies RNA sequences followed by gel Amplifies RNA sequences and identifies them
A B
separation according to size using a fluorescent probe
Amplifies DNA sequences and identifies them Amplifies DNA sequences and identifies them by
C D
using a fluorescent probe gel separation according to size

Amplifies RNA sequences and identifies them
E
based on mass : charge ratio
Explanation
analysis

Question 39 Cleavage stage embryo biopsy for pre-implantation genetic diagnosis
A Is typically undertaken 7 days after fertilization B Is undertaken at the 32-64 cell stage
Is facilitated by the addotion of calcium or

C Requires drilling of the zona pellucida D
magnesium to the culture medium
E Typically occurs at the 2-4 cells stage
Explanation
CLEAVAGE STAGE BIOPSY
• Undertaken at the 8-10 cell stage, 3 days after fertilisation
• 1-2 blastomeres are aspirated after drilling of the zona pellucida
• Zona drilling may be performed using acid Tyrodes solution, laser or by partial zona
dissection

• Compaction of the embryo begins to occur after the 8 cell stage with the formation
of inter-cellular junctions - this is Ca2+ / Mg2+ dependent. Biopsy is therefore facilitated
by using Ca2+ / Mg2+ free culture medium
Question 40 Malignant hyperpyrexia
Is characterized by a rise in body temperature

A Is an X-linked recessive condition B
triggered by exposure to certain antibiotics
Is characterized by muscle rigidity triggered by Is characterized by a massive rise in serum

C D
exposure to halothane amylase concentration during crises
Is characterized by a rise in body temperature

E
triggered by exposure to aspirin
Explanation
MALIGNANT HYPERPYREXIA
 Autosomal dominant
 Asymptomatic until exposed to succinylcholine or halothane during general
anaesthesia, producing muscle rigidity, rise in body temperature and high serum
creatinine
 60% mortality per episode ?
Question 41 Myotonic dystrophy

Severity remains consistent from one generation to
A Is characterized by proximal muscle weakness B
the next within a family
Is associated with unstable length mutation in the
C D Patients typically have difficulty clenching their fists
number of CTG repeats
E Is associated with red green colour blindness
Explanation
Myotonic Dystrophy
• Autosomal dominant
• Unstable length mutation in the number of CTG repeats
• Correlation between the length of the repeats and severity of the disease
• The length of the repeat may change during transmission, altering the severity of
the disease from one generation to the next
• Neonatal disease does not occur if the father has the disease. With maternal
disease, there is a 20% risk of neonatal death or severe neonatal hypotonia and mental
handicap

• Clinical features include frontal balding, distal muscle and sterno-mastoid
weakness, gonadal atrophy in males, difficulty relaxing a clenched fist, cardiac
conduction defects and retinopathy
• Pre-natal diagnosis by direct DNA analysis ?
Question 42 Which one is not an autosomal recessive disorder?
A Alpha-1-antitrypsin deficiency B Myotonic dystrophy
C Congenital adrenal hyperplasia D Cystinuria
E Cystic fibrosis
Explanation
 Myotonic dystrophy = autosomal dominant
Question 43 Congenital adrenal hyperplasia

Is due to 11-hydroxylase deficiency in the majority of
A Is an autosomal dominant disorder B
cases
C Affects 1 in 500 women in the UK D May present with neonatal vomiting and salt loss
E Is rare amongst Yupik Eskimos
Explanation
CONGENITAL ADRENAL HYPERPLASIA
 Autosomal recessive
 95% due to 21-hydroxylase deficiency
 Incidence 1:17,000 (UK), 1:500 Yupik Eskimos
Clinical
 Neonatal vomiting and shock from salt-losing
 Ambiguous genitalia ? virilisation of female fetus
 Precocious puberty in male
 Primary / secondary amenorrhoea with hirsutism and virilisation in late-onset type
 Elevated urinary ketosteroids and pregnanetriol
 Elevated plasma 17-hydroxyprogesterone and ACTH
 Normal life-span and fertility if promptly identified and treated with steroid replacement

Question 44 Mucopolysaccharidosis
A Are a group of autosomal recessive disorders B Are a group of X-linked recessive disorders
Are a group of autosomal dominant and autosomal

C Are a group of autosomal dominant disorders D
recessive disorders
Are a group of autosomal recessive and X-linked

E
recessive disorders
Explanation
MUCOPOLYSACCHARIDOSES
• Defective activity of the lysosomal enzymes, which blocks degradation of
mucopolysaccharides and leads to abnormal accumulation of heparan sulfate,
dermatan sulfate, and keratan sulfate.
• Seven types:
• Hurler syndrome (MPS IH)
• Hurler-Scheie syndrome (MPS I-H/S)
• Scheie syndrome (MPS IS)
• Hunter syndrome (MPS II)
• Sanfilippo syndrome (MPS III)
• Morquio syndrome (MP IV)
• Maroteaux-Lamy syndrome (MPS VI)
• Sly syndrome (MPS VII)
• All are autosomal recessive except type II (Hunter syndrome) which is X-

linked recessive.Type I = Hurler syndrome. *
• Type IV is associated with normal intelligence
Clinical features
Patients with MPS have normal development initially, with abnormalities appearing in
infancy or later in childhood.
• CNS disease – Hydrocephalus; cervical spine myelopathy
• Cardiovascular disease – Angina; valvular dysfunction; hypertension;
congestive heart failure
• Pulmonary disease – Airway obstruction, potentially leading to sleep apnea,
severe respiratory compromise, or cor pulmonale
• Ophthalmologic disease – Corneal clouding; glaucoma; chronic papilledema;
retinal degeneration
• Hearing impairment – Deafness
• Musculoskeletal disease – Short stature; joint stiffness; symptoms of
peripheral nerve entrapment

A 23 year old woman has sickle cell disease. Her partner is a carrier
Question 45 of the condition. The chances of their baby having sickle cell disease
is
A 1 in 2 B 1 in 4
C 3 in 4 D 100%
E 0%
Explanation
 Woman = SS
 Partner = SA
 1 in 2 chance of baby being SS
 100% chance of baby being carrier or affected
 1 in 2 chance of baby being carrier
 0% chance of baby being neither affected nor carrier
A 23 year old woman has sickle cell disease. Her partner is a carrier of the
Question 46
condition. The chances of their baby being normal is
A 1 in 2 B 1 in 4
C 3 in 4 D 100%
E 0%
Explanation
 Woman = SS
 Partner = SA

Question 47 Succinylcholine sensitivity
A Is an autosomal dominant condition B Is an X-linked recessive condition
C Is an X-linked dominant condition D Is an autosomal recessive condition
Typically presents at birth or within the first week of

E
life
Explanation
SUCCINYLCHOLINE SENSITIVITY
· Autosomal recessive
· Mutation in cholinesterase 1 gene resulting in cholinesterase deficiency
· Affected patients are asymptomatic until exposed to suxamethonium during
induction of general anaesthesia
Question 48 Alport syndrome is associated with
A Nephritis and sensori-neural deafness B Increased fragility of red blood cells
C Proximal muscle weakness D Cherry-red macular spot
E Androgen insensitivity
Explanation
ALPORT SYNDROME
· X-linked recessive; occurs in 1:5000 males
· Mutation in gene encoding for glomerullar basement membrane collagen
· Pre-natal diagnosis by DNA analysis
· Female carriers asymptomatic but have microscopic haematuria, 30% risk of
hypertension and 5-10% risk of chronic renal failure
· Associated with nephritis, proteinuria, and sensori-neural deafness


Question 49 Down’s syndrome is associated with
A Elevated maternal serum AFP levels B Elevated maternal unconjugated oestriol levels
C Elevated maternal serum HCG levels D Elevated maternal serum progesterone levels
E Low maternal serum placental growth factor levels
Explanation
DOWNS SYNDROME
• ? Trisomy 21
• ? 95% due to non-dysjunction in the FIRST meiotic division; 1-2%
mosaics, 3% unbalanced Robertsonian translocation
• ? Extra chromosome derived from the mother in 80-85% of cases
• ? Associated with increasing maternal age
• ? Associated with low AFP, low unconjugated oestriol and increased HCG
in maternal serum and increased nuchal thickening
Question 50 Tracheo-oesophageal fistula
A Tracheo-oesophageal fistula B Duodenal atresia
C Choroid plexus cysts D Gastroschisis
E Exomphalos
Explanation
TYPICAL CONGENITAL ANOMALIES
• ? CARDIAC - atrio-ventricular canal defects
• ? Duodenal atresia, also anal atresia
A 24 year old woman has a baby with Down’s syndrome, She is found to
Question 51 be a carrier of a t(14;21) balanced translocation. The risk of her having
another baby with Down’s syndrome is

A 1% B 15%
C 25% D 50%
E 100%
Explanation
RECURRENCE RISK
• ? No translocation - age related risk + 0.34% at term (0.42% mid-
trimester)
• ? Mother carrier of t(14;21) - 15% recurrence risk
• ? Father carrier of t(14;21) - 1% recurrence risk
• ? Mother or father carrier of t(21;21) - 100% recurrence risk
Question 52 Turner syndrome occurs in
A 1 in 5000 births B 1 in 5000 female births

C 1 in 50,000 births D 1 in 20,000 female births
E 1 in 500 births
Explanation
TURNER SYNDROME
· 45X, incidence 1:5000 female births; 99% of fetuses with 45X spontaneously
miscarry
· 50% have 45X, 25% are mosaics, 17% have an isochromosome of Xq. Other
abnormalities include ring X chromosome and Xp deletions. 4% have 45X/46XY
mosaicism which is associated with an increased risk of gonadoblastoma in dysgenetic
gonads
· In 80% of cases, only maternal X is present
· Recurrence risk close to population risk


AUTOSOMAL DOMINANT CONDITIONS
Question 1 Familial hypercholesterolaemia

A Is an autosomal recessive condition B Affects 1 in 500 males but 1 in 5000 females
C Affects 1 in 5000 females but 1 in 500 males D Affects 1 in 500 individuals
E Affects 1 in 5000 individuals
Explanation
HYPERCHOLESTEROLAEMIA (FAMILIAL)
• Onset in 30s - 40s with xanthelasma, xanthomata and corneal arcus and ischaemic
heart disease
• Population frequency 1:500
Question 2 Which one is not a typical feature of Marfan syndrome?

A Autosomal dominant inheritance B Lens subluxation
C Aortic aneurysms D Arachnodactyly
E Congenital absence of the vas deferens
Explanation
MARFAN SYNDROME
• 25% caused by new mutation
• Associated with lens subluxation, aortic aneurysm, arachnodactyly, long limbs and
joint laxity
• Average life-span 40-50 years

A Is an autosomal recessive condition B Is an X-linked recessive condition
Can present in the neonatal period if the mother
C Does not present in the neonatal period D
has the disease
Typically presents in the neonatal period if the
E
father has the disease

Explanation
Myotonic Dystrophy
handicap

Severity remains consistent from one generation to
A Is characterized by proximal muscle weakness B
the next within a family
Is associated with unstable length mutation in the
C D Patients typically have difficulty clenching their fists
number of CTG repeats
E Is associated with red green colour blindness
Explanation
Question 5 Osteogenesis imperfect

A Type I is an autosomal dominant disorder B Type II is an autosomal dominant disorder
C Type II is associated with a normal life span D Type I is associated with perinatal death
E Is a disorder of osteoblast function
Explanation
OSTEOGENESIS IMPERFECTA ?
• Genetic defect in collagen metabolism
• Type I - autosomal dominant, associated with recurrent fractures, blue sclera,
otosclerosis leading to conduction deafness. Normal life span

• Type II - variable inheritance with a 3% recurrence risk - causes perinatal death
with muntiple fractures at birth ?
Question 6 Which one is not a typical feature of osteogenesis imperfect type I?

A Blue sclera B Recurrent fractures
C Normal life span D Nerve conduction deafness
E Bone tumours
Explanation
Question 7 Which one is not an autosomal dominant disorder?

A Osteogenesis imperfecta type I B Alpha-1-anti-trypsin deficiency
C Otosclerosis D Myotonic dystrophy
E Facioscapulohumeral dystrophy
Explanation
 Alpha-1-anti-trypsin deficiency is autosomal recessive
Question 8 Which one is not an autosomal recessive disorder?

A Alpha-1-antitrypsin deficiency B Myotonic dystrophy
C Congenital adrenal hyperplasia D Cystinuria
E Cystic fibrosis
Explanation
 Myotonic dystrophy = autosomal dominant
Question 9 Alpha-1-antitrypsin deficiency

A Is an X-linked recessive disorder B Is an autosomal dominant disorder
Is associated with juvenile cirrhosis and Is characterized by a defect in the release of alpha-
C D
emphysema 1-antitrypsin from the pancreas
E Affects 3% of Caucasians

Explanation
ALPHA-1 ANTI-TRYPSIN DEFICIENCY
 Carrier frequency 3% in Caucasians
 Z-allele is a point mutation which interferes with the release of anti-trypsin from
hepatocytes
 Diagnosis made by protease inhibitor activity assay or DNA analysis (CVS or amnio)
 Associated with juvenile cirrhosis, emphysema
Question 10 Which one is not a typical feature of congenital adrenal hyperplasia?

A Primary amenorrhoea B Premature ovarian failure
C Secondary amenorrhoea D Elevated plasma ACTH
E Elevated plasma 17-hydroxyprogesterone
Explanation
Clinical
 Ambiguous genitalia - virilisation of female fetus
Can be diagnosed pre-natally using ultrasound Can be diagnosed pre-natally from amniotic
A B
scan fluid concentration of ACTH
Can be diagnosed pre-natally from amniotic Cannot be diagnosed pre-natally by chorionic

C D
fluid concentration of 17-hydroxyprogesterone villus sampling
E Affected fetuses cannot be treated in-utero

Explanation
· 95% due to 21-hydroxylase deficiency
· Incidence 1:17,000 (UK), 1:500 Yupik Eskimos
Clinical
· Neonatal vomiting and shock from salt-losing
· Ambiguous genitalia - virilisation of female fetus
· Precocious puberty in male
· Primary / secondary amenorrhoea with hirsutism and virilisation in late-onset type
· Elevated urinary ketosteroids and pregnanetriol
· Elevated plasma 17-hydroxyprogesterone and ACTH
· Normal life-span and fertility if promptly identified and treated with steroid
replacement
Pre-Natal Diagnosis
· 17-hydroxyprogesterone concentration in amniotic fluid or DNA analysis from CVS
or amniocentesis
· Maternal administration of dexamethasone to prevent virilisation of affected
female fetus
Question 12 Galactosaemia
A Is an X-linked recessive condition B Is an autosomal dominant condition
Is treated by exclusion of milk products from the diet
C Typically presents with neonatal hypoglycaemia D
for life
Is caused by a mutation in the galactose transferase
E
gene
Explanation
GALACTOSAEMIA
· Mutation in galactose-1-phosphate uridyl transferase gene
Clinical Features
· Neonatal vomiting, failure to thrive, jaundice, hepatomegaly, cataract
· Galactosuria
· Absent red cell galactose-1-phosphate uridyl transferase activity
· Treated by exclusion of milk products from diet for life. Delay in treatment (over
1month of age) results in learning disability
· Prenatal diagnosis by DNA analysis (CVS or amniocentesis), GLAT activity in
chorionic villi or amniocytes or amniotic fluid galacitol levels

Question 13 Which group of disorders are all inherited in an autosomal recessive manner?
Gaucher disease, Galactosaemia, haemochromatosis, Myotonic dystrophy, cystic fibrosis, Gaucher disease, sickle cell
A B
Von Willebrand disease disease
Sickle cell disease, Gaucher disease, Galactosaemia, Haemochromatosis, fascioscapulohumeral dystrophy,

C D
Haemochromatosis galactosaemia, sickle cell disease
Duchenne muscular dystrophy, cystic fibrosis, myotonic

E
dystrophy, Gaucher disease
Explanation
 Myotonic dystrophy, von Willebrand disease, fascioscapulohumeral dystrophy are
autosomal dominant
 Duchenne muscular dystrophy is X-linked recessive
Question 14 Mucopolysaccharidosis
Can be diagnosed pre-natally by measuring
A B Can be diagnosed pre-natally by karyotype
glycosaminoglycans in amniotic fluid
Can be diagnosed by measuring the activity of
C Can only be diagnosed by genetic testing D
mitochondrial enzymes
E Is typically diagnosed by tissue biopsy
Explanation
Diagnosis
• Pre-natal diagnosis possible by biochemical analysis of glycosaminoglycans in
amniotic fluid or by enzyme assay in cultured amniocytes or chorionic villi
Postnatal diagnostic studies that may be helpful include the following:
• Urinalysis, focusing on glycosaminoglycans (eg, dermatan sulfate, heparin
sulfate, and keratin sulfate)
• Serum assays for lysosomal enzymes (alpha-L-iduronidase, iduronate
sulfatase, heparan N -sulfatase, N -acetylglucosaminidase, alpha-glucosamine-
N -acetyltransferase, N -acetyl alpha-glucosamine-6-sulfatase, N -
acetylgalactosamine-6-sulfatase, N -acetylgalactosamine-6-sulfatase, B-
galactosidase, N -acetylgalactosamine-4-sulfatase, and B-glucuronidase)

Question 15 Phenylketonuria
Is caused by a deficiency of phenylalanine

A Is caused by a deficiency of phenylalanine B
hydroxylase
Is caused by a deficiency of phenylalanine Is caused by a deficiency of phenylalanine

C D
decarboxylase reductase
Is caused by a deficiency of phenylalanine

E
transporter protein in epithelial cells
Explanation
PHENYLKETONURIA
· Deficiency of phenylalanine hydroxylase
· Promptly treated with a low phenylalanine diet is associated with normal life span
although some degree of learning disability may be present
· After childhood (6-8years), the brain is less susceptible to the harmful effects of
high phenylalanine levels
· Risk of fetal structural abnormalities including microcephaly if treatment is not re-
introduced in an affected woman before conception
· Causes high blood and urine phenylalanine levels
· Neonatal screening using the Guthrie test
Question 16 If promptly recognized and treated, phenylketonuria is associated with

A Normal life-span and fertility B Normal life-span but reduced fertility
C Reduced fertility and reduced life-span D Reduced life-span bur normal fertility
Reduced life-span and reduced fertility but normal
E
IQ
Explanation
Question 17 Phenylketonuria
Requires treatment with a low phenylalanine diet Requires treatment with a low phenylalanine diet for
C D
during childhood and pregnancy only life

Requires treatment with a low phenylalanine diet
E
during childhood only
Explanation
Question 18
condition. The chances of their baby being a sickle cell carrier is
A 1 in 2 B 1 in 4
C 3 in 4 D 100%
E 0%
Explanation
 Woman = SS
 Partner = SA
Question 19
condition. The chances of their baby being normal is
A 1 in 2 B 1 in 4
C 3 in 4 D 100%
E 0%
Explanation
 Woman = SS
 Partner = SA

 0% chance of baby being neither affected nor ca
Question 20 Succinylcholine sensitivity

C Is an X-linked dominant condition D Is an autosomal recessive condition
E Typically presents at birth or within the first week of life
Explanation
SUCCINYLCHOLINE SENSITIVITY
· Mutation in cholinesterase 1 gene resulting in cholinesterase deficiency
· Affected patients are asymptomatic until exposed to suxamethonium during
induction of general anaesthesia
Question 21 Tay-Sachs disease

A Is an autosomal dominant condition B Affects 1 in 25 Ashkenazi Jews
C Is characterized by a cherry-red macular spot D Usually causes death by the age of 45 years
E Is more common in females than males
Explanation
TAY-SACHS DISEASE
• Autosomal recessive
• Mutation in beta-N-acetylhexosaminidase A gene
• Around 1 in 25 Ashkenazi Jewish people are carriers of the mutated gene
compared with around 1 in 250 people in the general population.With screening
methods for people at high risk, the condition is now rare and most cases now occur in
people who are not of Ashkenazi Jewish descent.
• It is estimated only about 1 in every 360,000 children born worldwide has Tay-
Sachs disease.
• Both males and females are equally affected by the condition
• 90% have cherry-red macular spot
• Pre-natal diagnosis by direct DNA analysis (CVS or amniocentesis) or by assay of
beta-N-acetylhexosaminidase A activity in chorionic villi or amniocytes
• Death usually by the age of 3-4 years.

A 23 year old woman attends the antenatal clinic at 10 weeks gestation. Her
Question 22
father has haemophilia A
There is a 50% chance that the woman’s child would be
A There is a 50% chance that the woman is a carrier B
a carrier
There is a 25% chance that the woman’s child would be There is a 75% chance that the woman’s child would
C D
a carrier have haemophilia A
There is a 50% chance that the woman’s child would
E
have haemophilia A
Explanation
X-linked recessive
· 100% chance that the woman is a carrier as she inherits affected X chromosome
from her father
· One in 4 children will have haemophilia, 1 in 4 will be carriers and 1 in 2 will be
normal
Question 23 With respect to the muscular dystrophies

Duchenne muscular dystrophy is X-linked recessive
Duchenne muscular dystrophy is characterized by
A while Becker muscular dystrophy is autosomal B
reduced dystrophin staining on muscle biopsy
recessive
Elevated serum creatinine can be used to screen for

Becker muscular dystrophy has a better prognosis
C D Becker muscular dystrophy but not Duchenne
than Duchenne muscular dystrophy
muscular dystrophy
Becker muscular dystrophy and myotonic dystrophy
E
are autosomal dominant disorders
Explanation
MUSCULAR DYSTROPHY *****
DUCHENNE
· X-linked recessive
· Null mutation resulting in absence of dystrophin on muscle biopsy
· Onset in childhood (by age of 5) with proximal muscle weakness, calf pseudo-
hypertrophy; mild learning disability in 25%, majority wheelchair bound by age 12 with
death in 20s.
BECKER
· X-linked recessive
· Reduced dystrophin on muscle biopsy

· Onset in late childhood, calf pseudo-hypertrophy. Wheelchair bound by age 25,
life-span may be normal - better prognosis than Duchenne
· Pre-natal diagnosis for Duchenne / Becker muscular dystrophy by direct DNA
analysis (CVS / Amnio)
· Carriers have elevated serum creatinine and can be used for screening
· In the absence of a family history, 2/3 of mothers of boys with Duchenne / Becker
muscular dystrophy will be carriers
In a baby with Downs syndrome, the probability of the extra

Question
chromosome 21 being maternal in origin is
24
A 100% B 95-100%
C 80-85% D 70-79%
E 50%
Explanation
DOWNS SYNDROME
• ? Trisomy 21
Question 25 Which one is not a typical clinical feature of Down’s syndrome?

A Talipes equinovarus B Fifth finger clinodactyly
C brachycephaly D Epicanthic folds
E Nystagmus
Explanation
CLINICAL FEATURES
1) GENERAL
• ? Neonatal hypotonia
• ? Learning disability
• ? Short stature

• ? Increased risk of Alzheimer's, hypothyroidism, acute leukaemia,
epilepsy and atlanto-axial instability
2) CRANIO-FACIAL
• ? Brushfield spots
• ? Brachycephaly
• ? Epicanthic folds
• ? Protruding tongue
• ? Upward sloping palpebral fissures
• ? Strabismus
• ? Nystagmus; congenital cataract
3) LIMBS
• ? Single palmar crease
• ? Fifth finger clinodactyly
A 24 year old woman has a baby with Down’s syndrome secondary to non-
Question 26
dysjunction. Her risk of having another baby with Down’s syndrome is
A 15% B Age-related risk

C 100% D 0.5%
E Age-related risk + 0.3%
Explanation
RECURRENCE RISK
trimester)
• ? Mother or father carrier of t(21
Question 27 Which one is not a typical feature of Klinefelter syndrome?

A Infertility B Increased risk of osteoporosis
C Gynaecomastia D Androgen insensitivity
E Small testicles

Explanation
Clinical Features
· Diagnosis typically made following infertility investigation - commonest cause of
hypogonadism and infertility in males
· Poorly developed secondary sexual characteristics, small testicles,
gynaecomastia, increased height (elongated limbs with)
· Low testosterone levels
· Gynaecomastia with increased risk of breast cancer
· Associated with increased risk of diabetes mellitus, osteoporosis, scoliosis and
emphysema
· IQ 10-20 points lower than siblings
· Infertility is universal except in mosaics
· Testosterone replacement at puberty / adulthood to promote development of
secondary sexual characteristics
Question 28 Turner syndrome occurs in
A 1 in 5000 births B 1 in 5000 female births
C 1 in 50,000 births D 1 in 20,000 female births
E 1 in 500 births
Explanation
TURNER SYNDROME
· 45X, incidence 1:5000 female births; 99% of fetuses with 45X spontaneously
miscarry
· 50% have 45X, 25% are mosaics, 17% have an isochromosome of Xq. Other
abnormalities include ring X chromosome and Xp deletions. 4% have 45X/46XY
mosaicism which is associated with an increased risk of gonadoblastoma in dysgenetic
gonads
· In 80% of cases, only maternal X is present
· Recurrence risk close to population risk
Question 29 Turner syndrome is associated with

A An increased risk of breast cancer B An increased risk of ovarian cancer
C An increased risk of endometrial cancer D An increased risk of Hashimoto’s thyroiditis
E An increased risk of renal failure

Explanation
Clinical Features
· Short stature with broad chest and widely spaced nipples; low hair line with
webbed neck
· Wide carrying angle and short 4th metacarpals and hypoplasia of the nails
· Peripheral lymphoedema
· Coarctation of the aorta and also atrial septal defects
· Primary amenorrhoea although menstruation may occur especially in mosaics;
absence of adolescent growth spurt and poorly developed secondary sexual
characteristics
· Increased risk of systemic hypertension, Hashimoto’s thyroiditis, Crohn’s disease,
GI bleeds
· Intelligence and life-span are normal
Question 30 Trisomy 13 is associated with
A Coarctation of the aorta B Holoproencephaly
C Duodenal atresia D Brushfield spots
E Cherry-red macular spot
Explanation
TRISOMY 13
· Incidence 1:5,000 live births
· Maternal age association
· Only 10% survive the first year
· Recurrence risk 100% in a t(13;13) carrier
· Typical features include holoproencephaly, cleft lip and palate, post-axial
polydactyly, scalp defects

Question 31 Which one is a type of chromosome heteromorphism?

A Balanced translocation B Unbalanced translocation
C Non-dysjunction D Fragile sites
E Gene deletions

Explanation
CHROMOSOME HETEROMORPHISMS
 These are variations in the amount of DNA present in particular chromosomes from
different individuals caused by variations in the size of repetitive DNA - they are
inherited rather than acquired
 The Y chromosome shows the greatest variation while the X chromosome shows the
least variation
There are 4 main groups of heteromorphisms
1) The size of Yq (long arm of Y chromosome) - 10% of normal males have a Yq
which is obviously shorter or longer than usual
2) Size of centromeric heterochromatin
3) Satellite polymorphisms - variations in the size of the satellite in acrocentric
chromosomes (13-15, 21, 22). Metacentric chromosomes do not have satellites
4) Fragile sites - constriction sites other than the centromere which are prone to
breakage. There are at least 80 common fragile sites. Most are not associated with any
clinical syndrome except the fragile site at Xq27.3 which is associated with learning
disability
Question 32 With respect to the structure of DNA

A DNA contains the base uracil B Nucleotides contain a nitrogenous base
C Nucleotides do not contain sugar molecules D Phosphate groups are found in RNA but not DNA
Bases are held together by 3-5-phosphodiester

E
bonds
Explanation
DNA STRUCTURE
· Nucleic acids (DNA or RNA) are made up of a chain of nucleotides
· Each nucleotide contains a nitrogenous base, a sugar molecule and a phosphate
group
· The base is either a purine (adenine and guanine) or a pyrimidine (cytosine,
thymine and uracil)
· Thymine occurs in DNA only while uracil occurs only in RNA *
· The sugar molecule is either ribose (RNA) or deoxyribose (DNA) and they are
held together by 3-5- phosphodiester bonds *
· The DNA molecule is made up of two chains of nucleotides held together by
hydrogen bonds between the bases
· A purine in one chain is always paired to a pyrimidine in the other chain: A-T; G-C
*
· The chain end terminated by the 5' carbon of the sugar molecule is the 5' end and
this always lies opposite the 3' end of the other strand. The two chains are arranged in a
double helix

Question 33 With respect to the structure of nucleic acids
A Thymine occurs in DNA but not RNA B Uracil occurs in DNA and RNA
C Cytosine occurs in RNA but not DNA D Uracil is always paired to Thymine in RNA
E Both cytosine and Thymine occur in RNA
Explanation
Question 34 Okazaki fragments

Are joined by DNA ligase to produce a continuous
A Are produced during RNA synthesis B
DNA molecule
C Are produced by DNA helicase D Are produced after enzyme digestion of DNA
E Are produced after enzyme digestion of RNA
Explanation
DNA REPLICATION
the DNA molecule

Question 35 With respect to the structure of chromosomes
One in three chromosomes do not have a The DNA double helix is coiled around spherical
A B
centromere histone beads to form nucleosomes
The DNA double helix coils around non-histone Chromatine fibres are coiled around histone
C D
proteins to form chromatin fibres beades to form the chromosome
The centromere is formed from chromatin fibres
E
coiled around the DNA double helix

Explanation
CHROMOSOME STRUCTURE
· Primary coiling of DNA into double helix
· Secondary coiling of double helix around spherical histone beads to form
nucleosomes
· Tertiary coiling of nucleosomes to form chromatin fibres
· Chromatine fibres form loops on a scaffold of non-histone acidic protein
· Chromatin fibres are wound into a tight coil to form chromosome
· All chromosomes have a centromere, the site of attachment of the spindle
apparatus during cell division
Question 36 Non-dysjunction
Occurring during meiosis I results in the gamete
Occurs during meiosis but does not occur during
A B receiving both homologues of the chromosome
mitosis
pair
Occurring in meiosis II results in the gamete
C receiving both homologues of the chromosome D Occurs during prophase
pair
E Accounts for 1-3% of cases of Down’s syndrome
Explanation
NON-DYSJUNCTION
· Failure of the chromosomal bivalents to segregate to the two daughter cells during
anaphase - can occur during meiosis I & II or during mitosis
· Occurring during meiosis I - the gamete receives both homologues of the
chromosome pair
· Occurring during meiosis II - the gamete receives two copies of one of the
homologues of the chromosome pair
· The majority of autosomal trisomies result from non-dysjunction during one of the
maternal meiotic division. The other daughter gamete inherits an autosomal monosomy
- always incompatible with survival to term
· Increased risk of non-dysjunction with increasing maternal age
Question 37 Reciprocal translocations

A Are also called Robertsonian translocations B Usually involve acrocentric chromosomes
C Most commonly involve chromosome 21 D Are always balanced
Carry a 1-10% risk of phenotypic abnormality in the
E
individual

Explanation
RECIPROCAL TRANSLOCATIONS
· Result from breakage of at least two metacentric chromosomes (centromere in the
middle) with exchange of genetic material
· Long arms of chromosomes 11 and 22 more commonly involved
· Incidence in general population ~1:500
· The total number of chromosomes is maintained at 46
· Individual with balanced reciprocal translocation phenotypically normal.
Segregation at meiosis may result in off-spring inheriting an unbalanced chromosomal
complement, resulting in an increased risk of miscarriage or congenital anomalies
· Risk of abnormal off-spring dependent on the particular chromosomal
rearrangement but lies between 1-10%
A 33 year old woman attends the antenatal clinic at 10 weeks gestation. She is a
Question 38
carrier of cystic fibrosis and her partner is also a carrier of cystic fibrosis.
All their children will either have cystic fibrosis or be There is a 1 in 2 chance that her offspring will have cystic
A B
carriers fibrosis
There is a 3 in 4 chance that her offspring will not have There is a 1 in 2 chance that her offspring will neither
C D
cystic fibrosis have the disease nor be a carrier
If the woman and her partner have different gene

E
mutations then all their children will be unaffected
Explanation
Autosomal recessive condition
· Woman and her partner have one abnormal allele
· 1 in 4 chance that an offspring inherits 2 normal alleles and 1 in 2 chance that
they inherit one normal allele (carrier). Carriers do not have the disease so 3 in 4
chance that offspring will not have the disease
Question 39 Which one is not an autosomal recessive condition?

A Sickle cell disease B Cystic fibrosis
C Phenylketonuria D Huntington’s disease
E Adrenogenital syndrome

Explanation
Examples of autosomal recessive conditions include: Cystic fibrosis, sickle cell disease,
phenylketonuria, adrenogenital syndrome, mucopolysaccharidoses, spinal muscular atrophy
Question 40 X-linked recessive conditions
A Mainly affect females B Cannot be transmitted from men to their sons
C Cannot be transmitted from women to their sons D Show a horizontal pedigree pattern
E Show a vertical pedigree pattern
Explanation
X-LINKED RECESSIVE INHERITANCE
· Males are affected predominantly *
· Male-male transmission never occurs. Unaffected males never transmit the
condition *
· Affected males transmit the allele to their daughters who become heterozygous
carriers and are almost always unaffected. Lyonisation (random inactivation of one X
chromosome) may result in some females having mild symptoms *
· Knight’s move pedigree pattern *
· The severity of the disease is uniform across generations *
· A woman with an affected son and an affected brother is an obligate carrier as the
possibility of two independent new mutations is extremely small. A woman with one
affected son is not an obligate carrier *
· Examples include: red-green colour blindness, Duchenne / Becker muscular
dystrophy, Haemophilia A / B, X-linked agammaglobulinaemia *

Question 41 X-linked dominant conditions
A Only affect males B Can be transmitted from father to son
C Include red-green colour blindness D Will affect all daughters of an affected male
E Include Duchenne muscular dystrophy
Explanation
X-LINKED DOMINANT INHERITANCE
· Males and females are affected

· The disease is uniformly severe in males but the degree of severity is variable in
females because of lyonisation
· Male-to-male transmission does not occur. All daughters of an affected male will
be affected. 1 in 2 sons of an affected female will be affected
· Main example is Vitamin D resistant rickets

sequences

E
programs
Explanation
technique
locations
analysis

A 1 in 200 B 1 in 400
C 1 in 1000 D 1 in 10,000
E 1 in 30,000

Explanation
Question 44 Which material / cells are used for fluorescent in-situ hybridization?
A Dividing (metaphase) cells B Non-dividing (interphase) cells
C Extracted DNA D Extracted RNA
E Extracted protein
Explanation
Question 45 Fluorescent quantitative polymerase chain reaction (QF-PCR)

Amplifies RNA sequences followed by gel Amplifies RNA sequences and identifies them using
A B
separation according to size a fluorescent probe
Amplifies DNA sequences and identifies them using Amplifies DNA sequences and identifies them by gel
C D
a fluorescent probe separation according to size
Amplifies RNA sequences and identifies them based
E
on mass : charge ratio
Explanation
analysis

Question 46 Which one is an autosomal dominant condition?

A Myotonic dystrophy B Duchenne muscular dystrophy
C Becker muscular dystrophy D Galactosaemia
E Sickle cell disease
Explanation
MUSCULAR DYSTROPHY?
Facioscapulohumeral ?
• Associated with moderate - severe disability - 20% wheelchair bound by age 40
• Proximal muscle waskness, peri-orbital and peri-oral muscle weakness ?
Myotonic Dystrophy
handicap
Question 47 Von Willebrand disease is characterized by

A X-linked recessive inheritance B Reduced platelet aggregation with ristocetin
C Quantitative deficiency of Factor X D Prolonged APTT
E Prolonged PT
Explanation
Von WILLEBRAND DISEASE
• Mostly autosomal dominant although some variants may be autosomal recessive

• Qualitative or quantitative defect in von Willebrand factor (vWF)
• vWF promotes platelet adhesion to sub-endothelium and binds and stalilises factor
VIII
• Factor VIII activity may be reduced
• Prolonged bleeding time and reduced platelet aggregation with ristocetin
• Infection, stress, inflammation, physical exercise and recent surgery and pregnancy
cause raised vWF and factor VIII levels

Is due to 11-hydroxylase deficiency in the majority
A Is an autosomal dominant disorder B
of cases
C Affects 1 in 500 women in the UK D May present with neonatal vomiting and salt loss
E Is rare amongst Yupik Eskimos
Explanation
Clinical
 Ambiguous genitalia ? virilisation of female fetus
Question 49 Freidreich’s ataxia

A Is an X-linked recessive disorder B Is an autosomal dominant disorder
Is the commonest inherited cause of cerebellar
C Is characterized by pes cavus and hyper-reflexia D
ataxia
Results in the individual being wheel-chair bound
E
by the age of 10 years
Explanation
FREIDREICH’S ATAXIA

· Commonest inherited cause of cerebellar ataxia
· Ataxia, pes cavus, loss of deep tendon reflexes and extensor plantar response
· Wheelchair bound by age 45
· Pre-natal diagnosis possible by DNA analysis (CVS or amniocentesis)
Question 50
condition. The chances of their baby having sickle cell disease is
A 1 in 2 B 1 in 4
C 3 in 4 D 100%
E 0%
Explanation
 Woman = SS
 Partner = SA
Question 51 Which one is not a typical feature of androgen insensitivity syndrome?

A 46XY karyotype B Infertility
C Normal breast development D Increased risk of gonadoblastoma
E Small hypoplastic uterus
Explanation
ANDROGEN INSENSITIVITY SYNDROME
· X-linked recessive *
· Mutation in androgen receptor gene
· Female phenotype, normal breast development, absent uterus with blind-ending
vagina; paucity of pubic and axillary hair *
· Testes found in abdomen or inguinal canal *
· Increased risk of gonadoblastoma *
· Infertility is universal
· Karyotype 46XY
· Risk of inguinal hernia increased *

Question 52 Down’s syndrome is associated with
A Elevated maternal serum AFP levels B Elevated maternal unconjugated oestriol levels
C Elevated maternal serum HCG levels D Elevated maternal serum progesterone levels
E Low maternal serum placental growth factor levels
Explanation
DOWNS SYNDROME
• ? Trisomy 21
A 24 year old woman has a baby with Down’s syndrome, She is found to
Question 53 be a carrier of a t(14;21) balanced translocation. The risk of her having
another baby with Down’s syndrome is
A 1% B 15%
C 25% D 50%
E 100%
Explanation
RECURRENCE RISK
trimester)
• ? Mother or father carrier of t(21;21) - 100% recurrence risk
Question 54 Trisomy 13 occurs in

A 1 in 500 births B 1 in 1000 births
C 1 in 2000 births D 1 in 5000 births
E 1 in 20,000 births

Explanation
TRISOMY 13
· Incidence 1:5,000 live births
· Maternal age association
· Only 10% survive the first year
· Recurrence risk 100% in a t(13;13) carrier
· Typical features include holoproencephaly, cleft lip and palate, post-axial
polydactyly, scalp defects


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This Copy is for Dr.

Question 1 Which fetal tissue is not typically used for karyotyping?

A 23 year old woman has undergone chorionic villus sampling

A Within 24h B In 24-48h

This Copy is for Dr. Mohamed ElHodiby

A Within 24h B In 24-48h

Question 4 For karyotype to be undertaken from peripheral blood

A Cell division is inhibited using antibiotics B Cell division is arrested in anaphase

This Copy is for Dr. Mohamed ElHodiby

Question 6 Chromosome heteromorphism

Question 7 With respect to the structure of DNA

This Copy is for Dr. Mohamed ElHodiby

Question 9 With respect to the structure of nucleic acids

E Both cytosine and Thymine occur in RNA

This Copy is for Dr. Mohamed ElHodiby

Occurs with the new DNA chain synthesized in the

Requires separation of the double helix by DNA

· Occurs during the S (synthesis) phase of the cell cycle

Question 11 DNA polymerase

C Digests the DNA molecule D Synthesizes RNA from DNA

E Synthesizes DNA from RNA

This Copy is for Dr. Mohamed ElHodiby

The DNA double helix is coiled around spherical

The centromere is formed from chromatin fibres coiled

Question 13 Reciprocal translocations

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There is no increase in risk because the translocation

This Copy is for Dr. Mohamed ElHodiby

Are expressed in homozygous but not

Tend to have the same disease severity in

Typically have a maternal age effect with respect

Question 16 Which disease is not an autosomal dominant condition?

This Copy is for Dr. Mohamed ElHodiby

Question 18 Autosomal dominant conditions

Are transmitted from male to female and from

This Copy is for Dr. Mohamed ElHodiby

A Sickle cell disease B Cystic fibrosis

C Phenylketonuria D Huntington’s disease

Circumstances in which females can be affected by X-linked recessive conditions

C The effect of variable expressivity D The effect of atypical lyonisation

E If the woman has an autosomal monosomy

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Question 22 Fluorescent in-situ hybridization

Uses fluorescently labeled gene-specific DNA

Cannot be used in Down’s syndrome screening

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Question 23 The false positive rate of fluorescent in-situ hybridization is

Question 25 Quantitative fluorescent PCR (QF-PCR)

Can be used to determine the expression of

E Relies on the amplification of RNA sequences

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Question 26 Pre-implantation genetic diagnosis

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BIOPSY FOR PRE-IMPLANTATION DIAGNOSIS

Question 28 During pre-implantation genetic diagnosis, allele drop-out can result in

This Copy is for Dr. Mohamed ElHodiby

Is associated with an increased risk of congenital

Question 30 The proportion of human pre-implantation embryos that show mosaicism is

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Question 32 With respect to the structure of chromosomes

Acrocentric chromosomes are usually involved in

E Acrocentric chromosomes do not have a centromere

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