Genetics - MCQs Flashcards
All but one of the following genomic variations will result in a change in the reading frame of a gene. Which one does not?
A. Single base pair deletion
B. Deletion of 12 base pairs
C. Duplication of 2 base pairs
D. Insertion of 8 base pairs
E. In/del (insertion of 2 base pairs with associated deletion of 9 base pairs)
B.
There are 3 base pairs to an mRNA codon, and 12 is divisible by 3. Therefore, a 12 base pair deletion will not change the reading frame, but will possibly change the amino acids encoded.
The locus of a gene refers to:
A. An alternative variant of a particular gene
B. The number of copies present during metaphase of mitosis
C. The location of the gene on a chromosome
D. Whether the gene was inherited from the child’s mother or father
C.
Gene expression is influenced by: A. Conformation of chromatin B. Methylation of DNA C. Availability of transcription factors D. None of the above E. All of the above
E.
Gene expression/regulation is influenced by processes known as ‘epigenetics’. All of the above mechanisms are examples of epigenetic processes.
A 17 year-old girl with short stature presents to the outpatient clinic. Which physical findings would be least consistent with a diagnosis of Turners Syndrome? A. Webbed neck B. Gingival hyperplasia C. Sheild shaped chest D. Normal IQ E. Lack of pubertal development
B.
Common physical features of Turners Syndrome include: short stature; heart-shaped face; webbed neck; shield chest; widely-spaced nipples; nail hypoplasia; and delayed puberty and infertility with streak ovaries.
Turners Syndrome is also commonly associated with: aortic coarctation; aortic valvular disease; renal anomalies; and intellectual disability.
A person with the karyotype 47XXY is most likely to have: A. Fragile X Syndrome phenotype B. Turners Syndrome female phenotype C. Normal female phenotype D. Normal male phenotype E. Klinefelters Syndrome male phenotype
E.
Klinefelters Syndrome affects males only, and is characterised by 1+ additional X-chromosomes such that the presence of more X-chromosomes is associated with a more severe phenotype (i.e. 48XXXY).
Clinically, this phenotype presents with: hypogonadism with small, firm testes; reduced secondary sexual characteristics; tall stature; gynaecomastia; low IQ; and behavioural difficulties such as impulsivity and poor judgement.
Dystrophinopathies, such as Duchenne Muscular Dystrophy and Beckers Muscular Dystrophy, are inherited in which manner: A. Autosomal recessive B. Autosomal dominant C. X-linked recessive D. X-linked dominant E. Spontaneous mutations to oncogenes
C.
The dystrophin gene responsible for muscular dystrophy is located on the X-chromosome. Duchenne and Beckers Muscular Dystrophy affects males and females are carriers. However, rarely there is skewed X-chromosome inactivation such that a female manifests signs of muscular dystrophy.
Differential expression of a gene according to its parent of origin is known as: A. Imprinting B. Epigenetics C. Hemizygosity D. Heteroplasmy E. Anticipation
A.
Imprinting is the epigenetic marking of a gene based on its parent of origin, and results in monoallelic expression. Therefore, imprinting is an epigenetic phenomenon, but epigenetics is not limited to only imprinting.
Hemizygosity occurs when there is only one copy of a gene in an otherwise diploid cell. This can occur in males when the gene is only present on the X or Y-chromosome.
Heteroplasmy occurs when there is more than one type of mitochondrial DNA present in a cell.
Anticipation is the observation that a particular phenotype seems to increase in severity in subsequent generations. Triplet repeat disorders are an example.
A patient with tall stature, joint laxity and a murmur presents to your clinic. Which of the following findings on ophthalmoscopy would be consistent with a diagnosis of Marfan Syndrome? A. Superior lens dislocation B. Inferior lens dislocation C. Papilloedema D. Stellate iris E. Normal eye examination
A.
Superior lens dislocation (aka ectopia lentis) is part of the clinical diagnostic criteria for Marfan Syndrome.
Inferior lens dislocation is associated with homocystinuria (another syndrome associated with tall stature).
Papilloedema is usually secondary to raised ICP.
Stellate iris can be seen in William Syndrome.
A male patient presents with unilateral visual disturbance. General examination reveals multiple café au lait patches and axillary freckling. Subsequent examination of his parents and siblings in unremarkable. The most likely genetic explanation for this presentation is:
A. Autosomal recessive inheritance
B. Aneuploidy
C. De novo mutation
D. Autosomal dominant inheritance with incomplete penetrance
E. Balanced Robertsonian translocation
C.
The patient presents with symptoms and signs suggestive of Neurofibromatosis type 1 (NF1). NF1 is caused by mutations in the NF1 tumour suppressor gene. Although inherited in an autosomal dominant fashion with high penetrance, up to 50% are new (de novo) mutations.
A young adult male presents with painless PR bleeding. Examination reveals a soft abdomen, no organomegaly, no perianal skin tags, and some small, pigmented spots which appear like freckles in the peri-oral region. His paternal grandfather died at age 55 from colorectal cancer, and his paternal aunt has had breast cancer. Colonoscopy reveals multiple hamartomatous polyps throughout the rectum and colon. The most likely cause of his condition is: A. Benign hamartomatous polyps B. Ulcerative colitis C. APC gene mutation D. Peutz-Jegher Syndrome E. BRCA-1 gene mutation
D.
Peutz-Jegher Syndrome usually presents with progressive gastrointestinal hamartomatous polyps, which may become malignant. It is an autosomal dominant condition, which also carries an increased risk of other cancers including breast and testicular. Most patients also have characteristic pigmented spots around the mouth, hands and feet.
Which pattern of inheritance is depicted below?
Autisomal dominant
A male patient presents with a 12-month history of lower back pain. You note that he is tall, with a lanky build and long fingers and toes. He has a high-arched palate and sternal deformity with scoliosis. His joints are hypermobile. His father died at age 50 with an unexplained “heart attack”. What is the most likely underlying genetic lesion? A. Mitochondrial mutation B. Chromosomal aneuploidy C. Biochemical pathway defect D. Point mutation in a single gene E. Chromosomal microdeletion
D.
FBN1 gene in Marfan Syndrome
Which one of the following statements about FISH is not true?
A. It is able to detect chromosomal aneuploidy
B. It is unable to detect triplet repeat expansions
C. It can be used to localise a translocated chromosomal segment
D. It is able to return results within 24 hours
E. It is able to detect exonic deletions
E.
FISH probe is too big to detect down to exonic level. It measures from gross to submicroscopic chromosomal level / ~1 mega base pairs only.
Which of the following tests is able to detect chromosomal aneuploidy? A. Conventional karyotype B. Microarray C. FISH D. All of the above E. None of the above
D.
The carrier frequency for cystic fibrosis in the Caucasian population in Australia is approximately 4%. The ΔF508 mutation accounts for 75% of all mutations among carriers in this population. A girl is diagnosed with cystic fibrosis. DNA studies identify one ΔF508 mutation, but fail to identify a mutation in the other allele. DNA studies of her unaffected brother are normal. What is the risk of the brother being a carrier? A. <1% B. 4% C. 25% D. 50% E. 66%
D.
The carrier frequency for a certain condition in the general population is 1:25. What is the chance that the person indicated in the pedigree below [?] has the condition? A. 1/50 B. 1/300 C. 2/3 D. 1/3 E. 1/4
B.
In the pedigree shown below, the affected male has a rare autosomal recessive disorder. His niece and nephew have a newborn son (indicated by the arrow). What is the chance that the baby will have the same disorder? A. 1 in 32 B. 1 in 28 C. 1 in 36 D. 1 in 64 E. 1 in 128
C.
In the rare autosomal recessive condition depicted in the pedigree below, what is the chance of the child marked as [?] being affected? A. 1 in 2 B. 1 in 4 C. 1 in 8 D. 1 in 16 E. 1 in 32
D.
Friedereich ataxia has a carrier frequency of 1 in 100. What is the incidence? A. 1 in 10,000 B. 1 in 20,000 C. 1 in 40,000 D. 1 in 50,000 E. 1 in 100,000
C.
For this you need to know that Freidereich ataxia is an autosomal recessive condition. This allows you to use the rule: incidence = (carrier frequency)^2 x 4.
The incidence of cystic fibrosis in the Caucasian population is 1 in 2,500. What is the carrier frequency? A. 1 in 10 B. 1 in 25 C. 1 in 50 D. 1 in 100 E. 1 in 250
B.
For this you need to know that CF is an autosomal recessive condition. This allows you to use the rule: incidence = (carrier frequency)^2 x 4, and work back.
If there are two alleles that have a frequency of 10% and 90%, respectively, what will be the frequency of the heterozygous genotype? A. 1% B. 9% C. 18% D. 81% E. 100%
C.
Some polymorphic loci on the Y-chromosome are homologous with polymorphic loci on the X-chromosome. DNA samples from six members of a family (parents and four children) have been analysed at one of these loci. These family members have DNA fragments of the following lengths visible on a gel after appropriate polymerase chain reaction (PCR) amplification of this locus.
Person Fragment length (in base pairs) Father 127,162 Mother 127,140 Daughter 127,140 Child 1 140,162 Child 2 127 Child 3 140
What is the most likely gender of Child 1, Child 2 and Child 3? Child 1 Child 2 Child 3 A. Female Male Male B. Female Female Male C. Female Male Female D. Male Female Female E. Male Female Male
D.
NB - Child 3 is hemizygous for 140, which must be the X-chromosome from their mother. This has resulted in monosomy X, i.e. Turner syndrome.
What is the mechanism of inheritance of the disorder depicted in the pedigree below? A. X-linked dominant B. X-linked recessive C. Maternal imprinting D. Paternal imprinting E. Mitochondrial
C.
What is the mechanism of inheritance of the disorder depicted in the pedigree below? A. X-linked dominant B. X-linked recessive C. Maternal imprinting D. Paternal imprinting E. Mitochondrial
D.
What are the possible inheritance mechanisms of the predigree below?
A. Autosomal recessive
B. Autosomal dominant with incomplete penetrance
C. X-linked recessive
D. X-linked dominant
E. Imprinting
Trick question
Could be B. or E.
What is the most likely inheritance pattern in this family?
A. Dominant inheritance with anticipation
B. Dominant inheritance with variable expressivity
C. Dominant inheritance with paternal imprinting
D. Dominant inheritance with maternal imprinting
E. Dominant inheritance with incomplete penetrance
D.
All affected individuals have it passed on from their father, approx. half the offspring of each affected male are affected, and none inherit it from their mother.
In the pedigree shown below, III:3 is a women of normal intelligence. She has a family history of mental retardation. Her nephew IV:1 and her cousin III:1 have recently been diagnosed with Fragile X Syndrome.
The risk that she is a Fragile X carrier is closest to: A. 100% B. 50% C. 25% D. 1% E. Nil
A.
First generation – 1:1 and 1:2: one carries an X with increased triplet repeats, but below disease threshold. This must be the mother, because both II:1 and II:2 are carriers (II:1 inherited an X from both parents, and II:2 could only have inherited his X from his mother). If it had come from the father, only the woman II:1 would be a carrier and none of subsequent generations from II:2 could be affected.
Next generation – II:1 and II:2: both must have inherited an affected X and be carriers. Despite carrying the mutation, it must still be below the disease threshold. Fathers pass their X to all of their daughters, so this means III:3 must then be a carrier. III:2 must also be a carrier, as the subsequent generation is affected.
A 16 year-old boy is referred for multiple skin lesions, some of which are shown in the photograph below. You make a presumptive diagnosis of neurofibromatosis type 1 (NF1), but he does not yet meet the diagnostic criteria for definitive diagnosis. Which of the following is not one of the diagnostic criteria for NF1? A. Vestibular Schwannoma B. Family history of NF1 C. Inguinal frecklin D. Lisch nodules E. Optic glioma
A.
A 26 year-old man presents to his GP with bilateral tinnitus and hearing loss. The MRI results are as shown.
What features suggests a diagnosis of neurofibromatosis type 2 (NF2)?
A. Bilateral vestibular Schwannoma
B. Cerebellar hypertrophy
C. Increased CSF volume
D. Midline shift
E. Optic glioma
A.
An 18 year-old boy with intellectual disability living in a residental care home is brought to you for re-evaluation of longstanding epilepsy. His seizures have been well controlled over the past 2 years. He had early-onset epilepsy, and has also been given a diagnosis of autism. You notice an unusual appearance to his fingernails, as shown below. Which one of the following is the most likely diagnosis? A. Fabry disease B. Lesch-Nyhan syndrome C. Neurofibromatosis D. Tuberous sclerosis E. Von Hippel-Lindau diease
D.
A 28 year-old man presents to the Emergency Department after a first seizure. He has a past history of significant learning difficulties and anxiety. He has distinctive facial features, as shown below. Which of the following is the most likely diagnosis? A. 22q11 B. Rett syndrome C. Neurofibromatosis D. Spinal muscular atrophy E. Fragile X syndrome
E.
A patient with the below karyotype is at increased risk of the following: A. Meningioma B. Acute lymphoblastic leukamia C. Melanoma D. Optic glioma E. Renal cell carcinoma
B.
The karyoptype is from a female individual with 3 copies of chromosome 21. Down Syndrome is associated with increased risk of leukaemia, both ALL and AML.
Meningiomas are associated with NF2.
Optic gliomas are associated with NF1.
Renal cell carcinomas are associated with tuberous sclerosis.
A child is referred to your clinic for consideration of non-accidental injury, having had multiple unexplained fractures. Which clinical feature might suggest the child has an underlying genetic condition which predisposes them to minimal-trauma fractures? A. Tall stature B. Short stature C. Blue sclerae D. Cardiac murmur E. Microcephaly
C.
Blue sclerae are associated with Oseteogenesis imperfecta, which causes brittle bones.
Which of the following is associated with tall stature? A. Noonan Syndrome B. Fanconi Anaemia C. Williams Sydnrome D. Achondroplasia E. Sotos Syndrome
E.
Sotos Syndrome is an overgrowth syndrome, which may be prenatal and postnatal. Growth velocity is particularly excessive in the first 3-4 years of life, and subsequently proceeds at the normal rate but remains in the high percentiles. Weight is usually appropriate for height. Advanced bone age present in 75-85% of patients.
Other typical characteristics include: macrocephaly with dolichocephaly (elongated); distinctive facies (long/narrow face with prominent forehead, high anterior hairline/frontal bossing, hypertelorism, down-slanting palpebral fissures, pointed chin, high/narrow palate); non-progressive neurological disorders (GM/FM/SL delay, incoordination, hypotonia); and intellectual disability (present in 80-85% patients). Other associations: neonatal jaundice; CHD (8-35%, usually not severe); GU tract abnormalities (~20%); CHL with increased frequency of URTIs; strabismus; scoliosis (~40%, usually not severe); premature teeth eruption (60-80%); and rarely tumours (<4%, incl. sacrococcygeal teratoma, neuroblastoma, presacral ganglioma, ALL). Ref: NORD Rare Diseases Database.
A-D are associated with short stature.
