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CASE FILES: BIOCHEMISTRY
A nsw ers
[12.1]
E. The correct diagnosis is thalassemia minor because the patient had
been asymptomatic until age 7 years. If he had thalassemia major or
Cooley anemia, he would have exhibited symptoms as early as his
first birthday. Pernicious anemia leads to a macrocytic or mega-
loblastic anemia, whereas aplastic anemia is characterized by normal
sized erythrocytes.
[12.2]
A. The iron chelator helps in excreting iron but has no role in increas-
ing red blood cell (RBC) production to counteract anemia.
[12.3]
D. Since the P-chain is decreased with respect to the a-chain, it is
most likely that there is a mutation that decreases the expression of
the P-chain gene, in which a mutation in the promoter region could
result. A point mutation in the P-chain leading to an amino acid sub-
stitution could lead to changes in electrophoretic mobility but would
not alter the levels of expression. A frameshift mutation in the P-chain
would result in decreased P-chain on the electrophoregram.
[12.4]
E. Thalassemia is autosomal recessive so Micawley Talltwin can get
the disease only if both the parents were to be heterozygotes (or a carrier)
of that particular trait.
B IO C H E M IS T R Y PE A R L S
The thalassemias are characterized by the absence or reduced syn-
thesis of one or more of the four globin chains of hemoglobin.
Thalassemias are named according to the affected globin chain;
thus, a disorder of the a-chain would be an a-thalassemia and a
disorder of the P-chain would be a P-thalassemia.
The
amplification refractory mutation system
(ARMS) is a tech-
nique in which the target DNA is amplified using a common
primer and either mutation specific primer for P-thalassemia or
the correct sequence primer to the target.
A
PCR restriction enzyme analysis
takes advantage of the occur-
rence of approximately 40 P-thalassemia mutations that either
introduce or remove a restriction endonuclease site.
Radio-labeled single stranded DNA oligonucleotide probes are
allowed to anneal with the target strand in an
oligonucleotide
hybridization analyses.
With one common mutation, a very successful and efficient
hybridization analysis is the
PCR allele-specific oligonucleotide
(ASO) assay.
This requires that the sequence of the common
mutation is known.
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