Genetics Flashcards
Which of the following is not a feature of neurofibromatosis type 1?
A. Schwannomas
B. Autosomal dominant inheritence
C. Optic pathway gliomas
D. Lisch nodules
E. Tibial bowing
A - Schwannomas
Key differences between NF1 and NF2:
- cafe au lait macules seen in both but less common in NF2
- lisch nodules are never seen in NF2
- neurofibromas in NF1, schwannomas in NF2 (particularly vestibular schwanommas i.e. acoustic neuromas)
- cognitive impairment in NF1, not in NF2
Which of the following genes is associated with HOCM?
A. MYBC3 gene
B. PKP2 gene
C. SCN5A gene
D. RYR2 gene
E. TTN gene
A. Cardiac mysosin binding 3 gene
PKP2 gene: arrythomogenic RV cardiomyopathy
SCN5A gene: LQTS (gain of function) and brugada (loss of function)
RYR2 gene: catecholaminergic polymorphic vt
TTN (titin) gene: dilated cardiomyopathy
Raised CK, proximal weakness and and mild cognitive impairment.
Gene and syndrome?
Duchenne’s muscular dystrophy
Mutation of dystropin (DMD) gene. X-linked, typically frameshift mutation due to deletion of one or more exons
Name the types of epigenetic mechanisms
- DNA methylation (hypo/hyper)
- histone modificatios (mehtylation, acetylation)
- chromatin modification
- X inactivation
- cellular differentiation
What is lyonization?
What does it cause?
X inactivation
Results in variable disease courses in women who are heterozygous for certain mutations inc. X linked diseases
In which of the following groups is the benefit of BRCA1/2 genetic testing most established?
A. Women 40 years of age
B. Men with breast cancer irrespective of age
C. Women 55yo with triple negative breast cancer
D. Women with epithelial ovarian cancer
A
B less well established
C <50yo + triple negative
D only for non-epithelioid ovarian cancer
Tumors associated with VHL
hemangioblastomas of the cerebellum and spine
retinal angiomas
clear cell renal cell cancers
pheochromocytomas/paragangliomas
neuroendocrine tumors of the pancreas
Define a missense mutation.
What does it result in?
Point mutation where a single base is change resulting in a single amino acid change
May lead to a loss of function, gain of function or altered function
Examples - sickle cell disease, proto-oncogenes
Define a nonsense mutation.
What does it result in?
Point mutation where a single base change results in a premature stop codon.
Leads to haploinsuffiency
List the following in their severity:
- frameshift mutation
- promotor mutation
- in frame mutation
Frameshift
In-frame
Promotor (variable pathogenecity)
NOD2 loss of function is associated with which autoimmune disease?
Crohn’s disease
ERAP1 deletion is protective for what
Ank spond
What is imprinting caused by?
Methylation of cytosine residues on paternal/maternal alleles
If 1 in 250,000 people have disease X, a non-lethal autosomal recessive disorder, what is the approximate carrier frequency of this disease?
a. 1/1000
b. 1/500
c. 1/250
d. 1/50
1/25
c) 1/250
People with disease X = qq = 1/250,000. √q² = √1/√25,000 = 1/500.
Carrier frequency = 2pq. Assume p = 1. 2 x 1/500 = 2/500 = 1/250.
For a given autosomal recessive disease q = 0.01. Approximately what percentage of the population has two copies of the normal allele?
a. 2%
b. 19%
c. 90%
95%
d. 98%
Answer: E
q = 0.01. p + q = 1. p = 1 – 0.01 = 0.99.
Two copies of the normal allele = PP. PP = 0.99 x 0.99 = 0.9801 = 98%.