Molecular Genetics Flashcards
Which of the following characteristics of a gene is most useful
in designing a sensitive mutation assay?
distribution frequency of mutations among different ethnic/racial groups
Which of the following characteristics of a DNA marker is most
important for accuracy in linkage studies?
low recombination rate with disease locus
In order to test for the homozygous deletion in patients affected with SMA which of the following
procedures must be accomplished initially
distinguish the telomeric (SMN1) SMN gene from the centromeric SMN (SMN2) gene
It is imperative to separate the SMN1 gene from the SMN2 gene before testing for the
homozygous deletion. This is most commonly done by using a restriction enzyme site present in
the SMN2 gene, but lacking in the SMN1 gene.
Which of the following molecular methods is a non-gel based assay for the detection of point
mutations?
A major advantage of dot blotting techniques is that gels are not used which allows one to screen
many samples.
PCR is most useful for which of the following DNA analyses?
Short Tandem Repeat (STR) analysis
RFLPs, while some can be detected by PCR, many cannot and require
Southern analysis. VNTRs are large repeating units and require Southerns, as do full expansions
for Fragile X and myotonic dystrophy
33 and a 300 GAA repeat. What is this person’s diagnosis?
Carrier of Friedreich ataxia
Only 4% of FRDA patients will have an expansion and a point mutation.
Most FRDA carriers will have an expansion and a normal allele. If this were a symptomatic
individual, one would recommend the point mutation analysis. For diagnostic testing, finding one
expansion confirms that the individual is at least a carrier but does not confirm the diagnosis,
although it is strongly suggestive.
Which of the following findings would be interpreted as a positive test result for Spinal Muscular
Atrophy
SMN1= telomeric, SMN2= centromeric
The important concept is that there are two SMN genes, one centromeric
and one telomeric. The pseudogene is centromeric, while the gene that causes SMA is telomeric.
Both genes are very similar at the molecular level and can be distinguished by SNPs in exons 7
and 8. Clinical laboratory testing is based on finding a homozygous deletion of exon 7 in the
SMNtel gene, so it is critical to be able to separate the SMNtel from the SMNcen. In most SMA
cases, a homozygous deletion of both exons 7 and 8 is found. However, the homozygous absence
of exon 7 is found in almost all SMA cases.
Achondroplasia has a high mutation rate and is most likely the result of which of the following
genetic concerns?
Methylated CG dinuceotide
A metastatic colorectal cancer patient is being tested to determine whether he is a good candidate
for imatanib therapy. Which of the following test results would be most favorable for
administering EGFR inhibitor therapy?
KRAS is downstream from EGFR. Auto-activating mutations that occur
in KRAS result in unregulated growth, thus bypassing EGFR regulation by inhibitor drugs. Prior
to prescribing EGFR inhibitors, patients are tested for KRAS mutations. Only in the absence of a
KRAS mutation is the mCRC patient placed on the EGFR inhibitor drug.
The targeted mutation panel of the assay is designed
to detect 90% of mutations reported in the database of clinically affected individuals.
The clinical sensitivity refers to the percent of patients that the assay will correctly identify. In this case, the disorder is autosomal recessive, indicating
that two mutations would be found in each patient. The assay detects 90% of the variants
found in the patient database. The clinical sensitivity is 0.9 x 0.9 = 0.81, or approximately
80%.
