Sickle Cell

embryonic hemoglobin aka ___ what chains?

Hb Gower 1 two zeta chains and two epsilon chains

which is the major adult hemoglobin?

HbA, two alpha chains and two beta chains

which subunits are found on chromosome 11? on chromosome 16?

chr 11: epsilon, delta, gamma, beta chr 16: alpha, zeta

what is the name of the defective protein produced by sickle cell patients?

hemoglobin S

what 3 factors promote polymerization of HbS?

high % HbS compared to other hemoglobin high concentration of HbS/dehydration low oxygen saturation/acidosis

In patients with sickle cell anemia, what will be elevated in the serum? why?

iron and bilirubin, degradation products of hemoglobin (from lysis of RBCs)

why do patients with sickle cell disease usually have anemia?

results from the reduced life span of the RBCs from 120 days to 10-20 days.

what are 5 common symptoms of sickle cell disease?

severe anemia frequent infections joint pains dyspnea poorly healing leg lesions

what are the chains of HbF?

two alpha and two gamma

what are the effects of sickled cells flowing through the blood stream?

vaso-occlusion microinfarcts in peripheral organs such as bones, lungs, liver, spleen, brain, and penis.

what effects do we see in sickle cell carriers?

are not anemic and have no clinical abnormalities can become symptomatic if exposed to extreme conditions like high altitude or physical exhaustion

what kind of genetic disease is sickle cell anemia?

autosomal recessive

what are the chains of HbA2?

minor adult hemoglobin (less than 3% of total); 2 alpha chains and 2 delta chains

what are the two specific genetic tests for SCD?

1) hemoglobin electrophoresis; based on proteins' surface charges 2) PCR and subsequent RE digestion

how many bands for beta-globin A? for beta-globin S? for a sample with both?

3 2 4

diseases due to a defective ___ gene only manifest after birth when HbA replaces HbF.

B globin

how does the sickle cell mutation relate to cutting sites?

if the mutation is present, there will be a loss of cutting site **note, Beta globin A and S are the SAME SIZES

what are reticulocytes? why does their number go up in SCD?

immature red blood cells compensatory RBC production

Why is the frequency of the sickle cell gene so high in malaria-endemic regions?

plasmodia cannot replicate very effectively in sickled red blood cells

where is the specific mutation that results in sickle cell anemia?

point mutation in the sixth codon of the beta-globin gene, located on chromosome 11. GAG --> GTG mutation means glutamic acid --> valine at position 6 of the hemoglobin beta chains

all hemoglobins contain two different pairs of peptide chains; what happens if the molarities of the chains are not equal?

thalassemias result

what causes the HbS molecules to polymerize?

the valine (that replaced glutamic acid) creates a hydrophobic patch on the surface of the HbS when the HbS molecules are deoxygenated, a "plug" is formed between this site and another.