Concept explainers
To write: A short essay to explain the molecular and cellular events leading to the heterozygotes individuals in sickle cell trait leading to the individual and population levels of biological organisation. .
Introduction:
Sickle cell disease is the most commonly occurring recessive inherited disorder found in African – Americans with an incidence of 1/400 and a carrier frequency of 1/10. It is caused due to the sickle cell allele that results in the structural and functional abnormality in normal haemoglobin. A point mutation that causes the substitution of glutamic acid by valine at 6th position of β-globin chain of haemoglobin is the main cause. The homozygous recessive individuals suffer severely from the disease; however the heterozygous carriers have the benefit of killing the malarial
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CAMPBELL BIOLOGY-W/MOD.MASTERBIOLOGY
- In one type of hemoglobin variant, lysine EF6 is replaced by an aspartic acid residue. What would be the effects of this mutation on the affinity of the hemoglobin for 2,3 BPG and oxygen? The affinity for 2,3-BPG would increase, and for oxygen would decrease. The affinity for 2,3-BPG would decrease, and for oxygen would decrease. The affinities for 2,3-BPG and for oxygen would be unaffected. The affinity for 2,3-BPG would increase, and for oxygen would increase. The affinity for 2,3-BPG would decrease, and for oxygen would increase.arrow_forwardWhen human hemoglobin undergoes a mutation, the mutant protein usually does not replace all of the normal HbA in the red blood cells or erythrocytes of the individual. The erythro- cytes contain mixtures of varying amounts of both HbA and the mutant protein depending on the mutation and the individual. Hb Yakima is a mutant human Hb with an Asp-(B99)His mutation. The diagram on the right shows that Hb Yakima was separated by DEAE-cellulose chromatography from HbA with a 0 – 0.1 M linear gradient of NaCl buffered to pH 8.3. Why is chromatog- raphy carried out at pH 8.3? If the isoelectric point of HbA is 6.85, what is the change in total charge caused by the mutation?How does the change in charge explain the chromatography elution profile of the Hb Yakima/HbA mixture? 1,5 -Hb-A Hb -Yakima 1.0 0.5- 20 40 60 80 00 Fraction number O.D578 nmarrow_forwardPlease helparrow_forward
- Normal Hgb is referred to as HbA and contains 4 subunits, 2 α-globin chains and 2 β-globin chains, arranged as two dimers of αβ. In Sickle Cell Disease, both β-globin chains are altered in the dimers (αβS/αβS). Q3: Which level of structure does the αβ/αβ and αβS/αβS in HbA and HbS describe?arrow_forwardPlease answer asap and in shortarrow_forwardGive typed full explanationarrow_forward
- Would this mutation result in protein binding BPG with lower affinity?arrow_forwardSickle cell anemia patients suffer from a distorted red blood cell shape and an anemic condition as a result of a genetic mutation in the HBB gene, which codes for the hemoglobin β subunits. This mutation changes a Glu to a Val at position 6 in the protein, and these patients express two alleles (one from each parent) with this mutation. When individuals inherit just one copy of this mutated gene, they are considered carriers, and have very few symptoms. Based on the quaternary structure of hemoglobin, what can you predict about the assembly of hemoglobin in sickle cell anemia patients versus carriers of the sickle cell trait? a. In sickle cell anemia patients, the α globin subunits have complementary mutations to ensure the quaternary structure of hemoglobin is attained. b. In sickle cell anemia patients, 100% of the hemoglobin is fully functional, whereas in those that carry the trait, there is no functional hemoglobin assembled. c. In individuals with the sickle cell…arrow_forwardCan you check if A is correct and please help answer the following questions?arrow_forward
- The hemoglobin in the fetus (HbF) is a structural variant of the hemoglobin in the mother (HbA). HbA is a tetrameric protein complex consisting of two α-globin and two β-globin subunits. HbF is made up of two αglobin and two γ-globin subunits, where the γ-globins are similar to the β-globins but γglobins have lower affinity for 2,3- bisphosphoglycerate or BPG. Studies of oxygen transport in pregnant mammals show that the oxygen-saturation curves between the red blood cells of the fetus and the mother are markedly different. 1. The shape of hemoglobin binding curves is: hyperbolic or sigmoidal 2. a) Based on the binding curves, determine the dissociation constant (Kd) for each hemoglobin complex. (Show correct units.) Kd of HbF + BPG: ________________ Kd of HbA + BPG: _____________________ b) Which has a higher affinity for oxygen? HbF+BPG HbA+BPG 3. a) How many BPG molecule(s) is/are expected to bind one hemoglobin complex? 1 2 3 4 b) BPG binding preferentially stabilizes which state…arrow_forward. Suggest probable conseauences of the following real or possible hemoglobin mutations. (a) At B146 (HC3) His → Asp (b) At B92 (F8) His Leu In each case, tell whether a single-nucleotide change is sufficient for the mutation.arrow_forwardBelow is the DNA base sequence for the normal protein for normal hemoglobin and the base sequence for (abnormal) sickle cell hemoglobin: Normal GGG CTT CTT TTT Sickle GGG CAT CTT TTT A)Transcribe and translate the normal and sickle cell DNA. B)Identify this as a point or frameshift mutation. Explain.arrow_forward
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