P globin chains

Sickle hemoglobin (HbS) differs from normal adult hemoglobin (HbA) at amino acid number 6 of the P-globin chain, where HbS has a Val and HbA a Glu. 

Two copies of the a-globin gene are designated a1 and o2. Each can provide a-globin chains that combine with p-globin chains. 

Each copy of ChrOiuusoiue 11 has only one gene for p-globin chains. 

The thalassemias are hereditary hemolytic diseases in which an imbalance occurs in the synthesis of globin chains. As a group, they are the most common single gene disorders in humans. Normally, synthesis of the a- and p-globin chains are coordinated, so that each a-globin chain has a p-globin chain partner. This leads to the forma... 

Thalassemias are hereditary hemolytic diseases in which an imbalance occurs in the synthesis of either a or 3 globin chains. Each thalassemia can be classified as either a disorder in which no globin chains are produced (a0- or p°-thalassemia), or in which some chains are synthesized but at a reduced rate (a+- or p+-thalassemia). [Note In p-thalassemias, synthe sis of p globin chains is decreased or absent, whereas in a-thalassemias, synthesis of a globin chains is decreased or absent.]... 

A. Diseases related to abnormal hemoglobin Sickle cell anemia results from a point mutation (GAG to GTG) that causes valine to replace glutamate at position 6 in the P-globin chain. In hemoglobin Wayne, deletion of a base causes a frameshift that produces the wrong sequence of amino acids in the chain beyond position 127. 

Hb H is an insoluble tetraraer consisting of four p-globin chains and arises in a-thalassemia in which there is a... 

These tests use either heat or isopropanol to precipitate the unstable Hb and must be performed on fresh blood. There are more than 100 unstable Hbs resulting mainly from the interchange of nonpolar amino acid residues for polar amino acid residues in positions in either the a- or P-globin chain associated with the heme cleft. Hb Hasharon (a47(CD) P ), an Hb variant found in Ashkenazi Jews,... 

P-Thalassemia major results from mutations that interfere with translation or are involved in the initiation, elongation, or termination of globin chain synthesis. Mutations that interfere with translation account for almost 50% of ail die p-thalassemia mutations. Included in this are frame shift or nonsense mutations that produce premature termination codons that result in incomplete translation of the P-globin gene and nonproduction of the P-globin chain resulting in P -thalassemia. 

The exception to the preceding description is the Sardinian type of 6P-thalassemia in which there are thalassemic indices on the CBC (low MCV and MCH, normal RDW) with a normal Hb concentration and an Hb F concentration between 15% and 20%. Hb Lepore is sometimes classified as a 8P-thaiassemia because of a reduction in the production of both 6- and p-globin chains or as an Hb variant because of the presence of an abnormal globin chain. 

Homozygous Hemoglobin S (HbSS). In homozygous Hb S, a valine for glutamic acid substitution occurs on both p-globin chains because of the inheritance of mutated P-globin chain genes from both parents. The condition is described as sickle cell anemia or sickle cell disease because of the sickle shaped RBCs that occur when there is a sickle cell crisis and is sometimes written as p p. ... 

Hemoglobin SC (Hb SC Disease). SC disease arises when both p-globin chains are substituted at position 6 with... 

Hemoglobin D Iran (b22(B4) " ° "). Hb D Iran is a p-globin chain variant in which glutamine replaces glutamic acid at position 22 of the p-globin chain. 

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