Genetics Flashcards
QUESTION 23 Parents of a child diagnosed with tuberous sclerosis want to know the risk of a 2nd child being born with the same condition. DNA analysis from the affected child of the gene TSC2 shows a pathogenic mutation. There is no family history of tuberous sclerosis. On physical examination and imaging, the father has multiple kidney angiomyolipomas. There is nothing else identified on examination or imaging of either parent. The child is identified to have a specific gene mutation for tuberous sclerosis on gene testing. The parents are tested and both have wild type genes. What is the most likely explanation for this? A. Non paternity B. Gonadal mosaicsm C. Laboratory error D. Uniparental disomy E. Somatic mosaicism F. Incomplete penetrance
E (Somatic mosaicism)
- The mosaicism explains why the father’s genetic testing could be negative and yet still have features of the condition.
- We only test the chromosomes of one/a few cells, and assume that that chromosomal pattern is universal throughout the body – in this case we assume that the entire body is free of the TSC gene but the father probably has some cells throughout the body with TSC mutation
- The father appears to display somatic mosaicism, not gonadal, as there is kidney involvement (somatic cells).
Gonadal mosaicism could explain the inheritance pattern of the son having a condition that wasn’t detected in the parents’ genotype (because the mutation is confined only to the germline cells, and even then to only some). However, it would not explain why the father has features of TSC in his kidneys, which are made up of somatic cells
Which cells undergo meiosis?
Gonadal cells
They end with 23 chromosomes
Name the gene and syndrome that matches with this phenotype:
Breast cancer and sarcoma in a 25F
TP53
Li Fraumeni
Name the gene and syndrome that matches with this phenotype:
Optic glioma with multiple cafe au lait spots
Neurofibromin 1
Neurofibromatosis 1
Name the gene and syndrome that matches with this phenotype:
Breast and follicular thyroid cancer
PTEN
Cowden Syndrome
Name the gene and syndrome that matches with this phenotype:
1000s of bowel polyps in a 20M
APC
FAP
Name the gene and syndrome that matches with this phenotype:
Parathyroid, pituitary and pancreatic adenomas
MENIN
MEN-1
Name the gene that matches with this phenotype:
Hereditary male breast cancer
BRCA 2
Name the gene and syndrome that matches with this phenotype:
Triple negative breast cancer
BRCA 1
Name the gene and syndrome that matches with this phenotype:
100s of bowel polyps in a 40yo who is APC gene negative
MUTYH
MUTYH polyposis
What is the probability of a being a carrier for a autosomal recessive condition if your sibling has the condition?
2/3
Freidrich ataxia has a carrier frequency of 1/100
What is the incidence?
Square, then multiply by 4
= 1/40,000
Cystic fibrosis has an incidence of 1/2,500
What is the carrier frequency?
1/25
Question 43
Small interfering RNAs (also called “micro-RNAs”) influence gene expression. The mechanism of action is best explained by their effect on:
A. gene promoter activation. B. gene promoter repression. C. RNA synthesis rate. D. RNA degradation rate. E. chromatin compaction.
D. RNA degradation rate – act by inducing degradation of mRNA prior to translation.
Question 23
Tumour suppressor genes are involved in the development of malignancy. What is the most likely
mechanism?
A. Missense mutation B. Telomerase inactivation C. Chromosome rearrangement D. Increased gene amplification E. Loss of heterozygosity
Loss of heterozygosity – this is one of the hallmarks of tumour suppressor gene activity
QUESTION 1
A 19-year-old female presents with short stature, neck webbing, wide spaced nipples and primary amenorrhea.
Which of the following is her most likely karyotype result?
A. 48,XXXX B. 46,XY C. 47,XXX D. 45,X E. 47,XXY
D. 45,X
QUESTION 68
Which one of the following mutation categories is most likely to result in a gene product with new or enhanced function?
A. Splicing mutation B. Nonsense mutation C. Missense mutation D. Silent mutation E. Promoter mutation
C. Missense mutation – best answer. Refers to substitution that changes a single base pair resulting in the codon producing a single different amino acid (which may be conservative or non-conservative). The size of the mRNA and protein are not changed, but the composition and sometimes the function (non-conservative) of the protein does change and this may be increased function or decreased function or altered function.
QUESTION 2010 B3
Parents of a child with a rare autosomal dominant genetic disorder asking for advice re: the risk for
future pregnancy. The mutated gene is identified in the child, and he expresses the phenotype.
However, both the mother and father do not have this mutation nor are they symptomatic. The most
likely cause for this is
A. Lab error
B. Non-paternity
C. Incomplete penetrance
D. Mosacism
E. Expressivity
D - Mosaicism
Which of the following observations regarding a rare disorder would provide the best evidence of autosomal dominant inheritance? A. Father and son affected B. Father and daughter affected C. Mother and son affected D. Mother and daughter affected E. Male and female cousins affected
A. Father and son affected
Achondroplasia is an autosomal dominant condition. Heterozygotes have achondroplasia, while
homozygotes usually die at birth. If two people with achondroplasia meet and marry, what is the
probable outcome for their children?
a. 25% achondroplasia, 50% normal, 25% perinatal death
b. 25% normal, 50% achondroplasia, 25% perinatal death
c. 25% normal, 50% perinatal death, 25% achondroplasia
d. 25% achondroplasia, 50% perinatal death, 25% normal
e. 50% achondroplasia, 50% normal
B - 25% normal, 50% achondroplasia, 25% perinatal death
QUESTION 2012 A40
Trisomy 21 is associated with multi-system functional impairment. However trisomy of the X chromosome often results in a normal phenotype or mild problems with behavior, coordination and tall stature. What is the primary explanation for the milder phenotype in trisomy X?
A. X chromosome imprinting
B. X chromosome inactivation
C. Less genes on the X chromosome
D. Different mechanism of action in embryogenesis
E. X chromosome pathology is not dosage dependent
B - X chromosome inactivation
Some autosomal recessive diseases have high prevalence in particular populations, even though they are often fatal (e.g. Alpha thalassaemia in South East Asia; G6PD deficiency in the Mediterranean). Which of the following is the most likely explanation?
A. Consanguinity.
B. High mutation rates in specific populations.
C. Survival advantage in heterozygous carriers.
D. Survival advantage in wild type homozygotes.
E. Founder effect
C – correct; thalassaemia and G6PD protective against malaria
Genetic 2010A Q30
An autosomal recessive disease has an incidence of 1 in 6400. What is the carrier frequency?
A. 1/20 B. 1/40 C. 1/60 D. 1/80 E. 1/120
B - 1/40
Question 94 Angela and Robert are a married couple who come to see you with regards to a planned pregnancy. They met at a cystic fibrosis support group and each has a sibling with cystic fibrosis. Both Angela and Robert are healthy. What is the probability that they will have a child with cystic fibrosis? A. 1/2 B. 1/4 C. 1/9 D. 1/16 E. 1/25
2/3 x 2/3 = probability that they are both carriers
Then we need to work out the probability that they will have a child with the disease if they are both carriers • there is a ¼ chance of aa (child being affected)
So 2/3 x 2/3 x 1/4 = 1/9
C - 1/9
Question A 23 year old man presents with café au lait spots and cutaneous neurofibromas in his leftarm only. What is the genetic predisposition for this presentation? A. Chimerism B. Gonadal mosaicism C. Heteroplasmy D. Skewed X- inactivation E. Somatic mosaicism
E - somatic mosaicism
Genetics 2006A Question 50
Which one of the following statements is the best description of the molecular basis of a chimeric (fusion) protein (eg Bcr-Abl)?
A. Formation of disulphide bonds between cytosine residues on different peptides.
B. Post-transcription ligation of non-homologous messenger RNA (mRNA) molecules.
C. Hybrid messenger RNA (mRNA) synthesis from a bi-directional promoter.
D. Deletion of an exon from one gene.
E. In-frame ligation of the 5-end of one gene to the 3-end of another.
E. In-frame ligation of the 5-end of one gene to the 3-end of another.
What is the most distinguishing feature of loss of imprinting of a growth-promoting imprinted gene?
A. Restoration of normal methylation patterns.
B. Inhibition of cell growth.
C. Reduced expression of the imprinted gene product. D. Activation of the normally silent allele.
E. Ablation of biallelic gene expression
D – correct; loss of imprinting causes allele to be express
2008 QUESTION 37 The concept that genetic counselling should be nondirective arises mostly from respect for which of the following principles of medical ethics? A. Justice. B. Beneficence. C. Autonomy. D. Non-maleficence. E. Dignity.
C - autonomy
